Pub Date : 2023-05-01DOI: 10.1016/j.xfss.2023.03.003
Reeva B. Makhijani M.D. , Alison F. Bartolucci Ph.D. , Cindy A. Pru M.S. , James K. Pru Ph.D. , John J. Peluso Ph.D.
Objective
To determine the relationship between the levels of cumulus cell (CC) hemoglobin messenger ribonucleic acid (mRNA) and the developmental potential of the associated oocyte and whether hemoglobin protects the CCs from oxidative stress–induced apoptosis.
Design
Laboratory-based study.
Setting
University laboratory and university-affiliated in vitro fertilization center.
Patient(s)
Cumulus cells from the oocytes of patients who underwent in vitro fertilization with intracytoplasmic sperm injection with and without preimplantation genetic testing between 2018 and 2020.
Intervention(s)
Studies on individual and pooled CCs collected at the time of oocyte retrieval or cultured under 20% or 5% O2.
Main Outcome Measure(s)
Quantitative polymerase chain reaction analysis of individual and pooled patient CC samples were used to monitor the hemoglobin mRNA levels. Reverse transcription-polymerase chain reaction arrays were used to assess genes that regulate oxidative stress in CCs associated with aneuploid and euploid blastocysts. Studies were conducted to assess the effect of oxidative stress on the rate of apoptosis, level of reactive oxygen species, and gene expression in CCs in vitro.
Result(s)
Compared with CCs associated with arrested and aneuploid blastocysts, the mRNA levels encoding the alpha and beta chains of hemoglobin increased by 2.9- and 2.3-fold in CCs associated with euploid blastocysts, respectively. The mRNA levels encoding the alpha and beta chains of hemoglobin also increased by 3.8- and 4.5-fold in CCs cultured under 5% O2 vs. 20% O2, respectively, and multiple regulators of oxidative stress were overexpressed in cells cultured under 20% O2 compared with those under 5% O2. However, the rate of apoptosis and amount of mitochondrial reactive oxidative species increased by 1.25-fold in CCs cultured under 20% O2 compared with those under 5% O2. Variable amounts of the alpha and beta chains of hemoglobin were also detected within the zona pellucida and oocytes.
Conclusion(s)
Higher levels of nonerythroid hemoglobin in CCs are associated with oocytes that result in euploid blastocysts. Hemoglobin may protect CCs from oxidative stress–induced apoptosis, which may enhance cumulus-oocyte interactions. Moreover, CC-derived hemoglobin may be transferred to the oocytes and protect it from the adverse effects of oxidative stress that occurs in vivo and in vitro.
{"title":"Nonerythroid hemoglobin promotes human cumulus cell viability and the developmental capacity of the human oocyte","authors":"Reeva B. Makhijani M.D. , Alison F. Bartolucci Ph.D. , Cindy A. Pru M.S. , James K. Pru Ph.D. , John J. Peluso Ph.D.","doi":"10.1016/j.xfss.2023.03.003","DOIUrl":"10.1016/j.xfss.2023.03.003","url":null,"abstract":"<div><h3>Objective</h3><p>To determine the relationship between the levels of cumulus cell<span> (CC) hemoglobin messenger ribonucleic acid (mRNA) and the developmental potential of the associated oocyte and whether hemoglobin protects the CCs from oxidative stress–induced apoptosis.</span></p></div><div><h3>Design</h3><p>Laboratory-based study.</p></div><div><h3>Setting</h3><p>University laboratory and university-affiliated in vitro fertilization center.</p></div><div><h3>Patient(s)</h3><p>Cumulus cells from the oocytes of patients who underwent in vitro fertilization with intracytoplasmic sperm injection with and without preimplantation genetic testing between 2018 and 2020.</p></div><div><h3>Intervention(s)</h3><p><span>Studies on individual and pooled CCs collected at the time of oocyte retrieval or cultured under 20% or 5% O</span><sub>2</sub>.</p></div><div><h3>Main Outcome Measure(s)</h3><p><span>Quantitative polymerase chain reaction analysis of individual and pooled patient CC samples were used to monitor the hemoglobin mRNA levels. Reverse transcription-polymerase chain reaction arrays were used to assess genes that regulate oxidative stress in CCs associated with </span>aneuploid<span><span> and euploid blastocysts. Studies were conducted to assess the effect of oxidative stress on the rate of apoptosis, level of </span>reactive oxygen species, and gene expression in CCs in vitro.</span></p></div><div><h3>Result(s)</h3><p>Compared with CCs associated with arrested and aneuploid blastocysts, the mRNA levels encoding the alpha and beta chains of hemoglobin increased by 2.9- and 2.3-fold in CCs associated with euploid blastocysts, respectively. The mRNA levels encoding the alpha and beta chains of hemoglobin also increased by 3.8- and 4.5-fold in CCs cultured under 5% O<sub>2</sub> vs. 20% O<sub>2</sub>, respectively, and multiple regulators of oxidative stress were overexpressed in cells cultured under 20% O<sub>2</sub> compared with those under 5% O<sub>2</sub>. However, the rate of apoptosis and amount of mitochondrial reactive oxidative species increased by 1.25-fold in CCs cultured under 20% O<sub>2</sub> compared with those under 5% O<sub>2</sub><span>. Variable amounts of the alpha and beta chains of hemoglobin were also detected within the zona pellucida and oocytes.</span></p></div><div><h3>Conclusion(s)</h3><p>Higher levels of nonerythroid hemoglobin in CCs are associated with oocytes that result in euploid blastocysts. Hemoglobin may protect CCs from oxidative stress–induced apoptosis, which may enhance cumulus-oocyte interactions. Moreover, CC-derived hemoglobin may be transferred to the oocytes and protect it from the adverse effects of oxidative stress that occurs in vivo and in vitro.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 2","pages":"Pages 121-132"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1016/j.xfss.2023.03.005
Ramya Sethuram M.D. , Melissa Bukowski B.Sc. , Francis Hernandez B.Sc. , Yuan You B.Sc. , Elizabeth Puscheck M.D. , Gil Mor M.D. , Pancharatnam Jeyasuria Ph.D. , Jennifer C. Condon Ph.D.
Objective
To gain an understanding of the potential role of endoplasmic reticulum (ER) stress in the endometrial compartment during early pregnancy, a highly understudied area.
Design
This study examined the regulation of interferon-β (IFNβ) in response to ER stress in human decidualized and nondecidualized endometrial cells (human endometrial stromal cells [HESCs]) in vitro. In vivo, we examined ER stress and the IFNβ levels locally in the mouse endometrium before and after implantation at embryonic day (E)1, E3, and E6.
Setting
The study was performed in a reproductive sciences laboratory for Human Growth and Development.
Patient(s)
None.
Intervention(s)
None.
Main Outcome Measure(s)
Quantitative polymerase chain reaction, Western blotting, and immunohistochemical analysis allowed us to test the action of endogenous ER stress activation in the endometrial compartment likely triggered by implantation and its ability to increase the endometrial IFNβ levels.
Result(s)
In vitro, we observed a significant difference in the IFNβ levels in HESCs, in response to ER stress activation, where decidualized HESCs exhibited a threefold increase in the IFNβ levels compared with nondecidualized HESCs. Apoptotic caspase-3 activation was also isolated to the decidualized cells as a result of ER stress–dependent suppression of nuclear factor-kappa beta–regulated antiapoptotic factors, XIAP and MCL-1. In vivo, mouse endometrial IFNβ was present in F4/80-positive macrophages at all time points examined. After implantation (E6), the mouse luminal epithelial cells robustly coexpressed both IFNβ and the ER stress marker immunoglobulin heavy chain binding protein (BiP).
Conclusion(s)
These analyses demonstrate that both in vivo and in vitro, differentiated and decidualized endometrial cells undergoing ER stress have the capacity to produce increased IFNβ levels; therefore, ER stress activation in the endometrial compartment may play a vital role in promoting successful implantation events.
{"title":"Endoplasmic reticulum stress response and the regulation of endometrial interferon-beta production","authors":"Ramya Sethuram M.D. , Melissa Bukowski B.Sc. , Francis Hernandez B.Sc. , Yuan You B.Sc. , Elizabeth Puscheck M.D. , Gil Mor M.D. , Pancharatnam Jeyasuria Ph.D. , Jennifer C. Condon Ph.D.","doi":"10.1016/j.xfss.2023.03.005","DOIUrl":"10.1016/j.xfss.2023.03.005","url":null,"abstract":"<div><h3>Objective</h3><p>To gain an understanding of the potential role of endoplasmic reticulum (ER) stress in the endometrial compartment during early pregnancy, a highly understudied area.</p></div><div><h3>Design</h3><p>This study examined the regulation of interferon-β (IFNβ) in response to ER stress in human decidualized and nondecidualized endometrial cells (human endometrial stromal cells<span> [HESCs]) in vitro. In vivo, we examined ER stress and the IFNβ levels locally in the mouse endometrium before and after implantation at embryonic day (E)1, E3, and E6.</span></p></div><div><h3>Setting</h3><p>The study was performed in a reproductive sciences laboratory for Human Growth and Development.</p></div><div><h3>Patient(s)</h3><p>None.</p></div><div><h3>Intervention(s)</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Quantitative polymerase chain reaction, Western blotting, and immunohistochemical analysis allowed us to test the action of endogenous ER stress activation in the endometrial compartment likely triggered by implantation and its ability to increase the endometrial IFNβ levels.</p></div><div><h3>Result(s)</h3><p><span>In vitro, we observed a significant difference in the IFNβ levels in HESCs, in response to ER stress activation, where decidualized HESCs exhibited a threefold increase in the IFNβ levels compared with nondecidualized HESCs. Apoptotic caspase-3 activation was also isolated to the decidualized cells as a result of ER stress–dependent suppression of nuclear factor-kappa beta–regulated antiapoptotic<span> factors, XIAP and MCL-1. In vivo, mouse endometrial IFNβ was present in F4/80-positive macrophages at all time points examined. After implantation (E6), the mouse luminal epithelial cells robustly coexpressed both IFNβ and the ER stress marker </span></span>immunoglobulin heavy chain binding protein (BiP).</p></div><div><h3>Conclusion(s)</h3><p>These analyses demonstrate that both in vivo and in vitro, differentiated and decidualized endometrial cells undergoing ER stress have the capacity to produce increased IFNβ levels; therefore, ER stress activation in the endometrial compartment may play a vital role in promoting successful implantation events.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 2","pages":"Pages 151-162"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9529583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1016/j.xfss.2022.12.003
Sicily E. Garvin M.D. , Chandrashekara Kyathanahalli Ph.D. , Sohail Soha B.S. , Jennifer C. Condon Ph.D. , Pancharatnam Jeyasuria Ph.D.
Objective
To examine the activation and consequence of uterine apoptotic caspase-3 action on 1 day after coitus (dpc) in the pregnant mouse. We have previously demonstrated that in a pregnant uterus, caspase-3 activation from mid to late gestation isolated to the myometrial compartment is largely nonapoptotic and controls uterine quiescence. Additionally, we had demonstrated that apoptotic caspase-3 activation isolated to the endometrial compartment at term regulated endometrial prostaglandin synthesis.
Design
Uteri were isolated from pseudopregnant and nonligated controls and unilateral and bilateral ligated uterine horn mouse models at 1, 3, and 6 dpc. Uteri were examined for apoptotic indices, such as caspase-3 activation and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining. Immunohistochemical analysis identified the site of uterine apoptotic caspase-3 activation. The truncated form of phospholipase A2 was examined as a measure of apoptotic caspase-3–mediated calcium independent phospholipase A2 (iPLA2) activation.
Result(s)
We identified the site and impact of uterine apoptotic caspase-3 activation using uteri isolated from nonpregnant control animals at estrous and diestrous and control pregnant mice at 1–19 dpc. Our analysis revealed that apoptotic caspase-3 and iPLA2 activation were limited to the endometrial compartments of the control and unilateral ligated uteri on 1 dpc and were not found in the pseudopregnant or bilateral ligated uterine horn or on 3 or 6 dpc in the control and unilateral ligated uteri.
Conclusion(s)
In this study, we determined that uterine caspase-3 activation on 1 dpc, which is endometrial and apoptotic in nature, may play a potential role in regulating the previously reported preimplantation surge in endometrial PGE2 synthesis through apoptotic caspase-3–mediated iPLA2 activation. Our data indicate that the presence of a conceptus on 1 dpc likely triggers an increase in endometrial apoptotic caspase-3–mediated iPLA2 activation. When activated, iPLA2 causes the hydrolysis of fatty acids, resulting in arachidonic acid release and PGE2 production, which has been demonstrated to act in a leutoprotective manner in early pregnancy, prolonging progesterone synthesis and promoting uterine receptivity.
{"title":"Preimplantation apoptotic endometrial caspase-3–mediated phospholipase A2 activation: a potential component in programming uterine receptivity","authors":"Sicily E. Garvin M.D. , Chandrashekara Kyathanahalli Ph.D. , Sohail Soha B.S. , Jennifer C. Condon Ph.D. , Pancharatnam Jeyasuria Ph.D.","doi":"10.1016/j.xfss.2022.12.003","DOIUrl":"10.1016/j.xfss.2022.12.003","url":null,"abstract":"<div><h3>Objective</h3><p>To examine the activation and consequence of uterine apoptotic caspase-3 action on 1 day after coitus (dpc) in the pregnant mouse. We have previously demonstrated that in a pregnant uterus, caspase-3 activation from mid to late gestation isolated to the myometrial compartment is largely nonapoptotic and controls uterine quiescence. Additionally, we had demonstrated that apoptotic caspase-3 activation isolated to the endometrial compartment at term regulated endometrial prostaglandin synthesis.</p></div><div><h3>Design</h3><p>Uteri were isolated from pseudopregnant and nonligated controls and unilateral and bilateral ligated uterine horn mouse models at 1, 3, and 6 dpc. Uteri were examined for apoptotic indices, such as caspase-3 activation and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining. Immunohistochemical analysis identified the site of uterine apoptotic caspase-3 activation. The truncated form of phospholipase A2 was examined as a measure of apoptotic caspase-3–mediated calcium independent phospholipase A2 (iPLA2) activation.</p></div><div><h3>Result(s)</h3><p>We identified the site and impact of uterine apoptotic caspase-3 activation using uteri isolated from nonpregnant control animals at estrous and diestrous and control pregnant mice at 1–19 dpc. Our analysis revealed that apoptotic caspase-3 and iPLA2 activation were limited to the endometrial compartments of the control and unilateral ligated uteri on 1 dpc and were not found in the pseudopregnant or bilateral ligated uterine horn or on 3 or 6 dpc in the control and unilateral ligated uteri.</p></div><div><h3>Conclusion(s)</h3><p>In this study, we determined that uterine caspase-3 activation on 1 dpc, which is endometrial and apoptotic in nature, may play a potential role in regulating the previously reported preimplantation surge in endometrial PGE2 synthesis through apoptotic caspase-3–mediated iPLA2 activation. Our data indicate that the presence of a conceptus on 1 dpc likely triggers an increase in endometrial apoptotic caspase-3–mediated iPLA2 activation. When activated, iPLA2 causes the hydrolysis of fatty acids, resulting in arachidonic acid release and PGE2 production, which has been demonstrated to act in a leutoprotective manner in early pregnancy, prolonging progesterone synthesis and promoting uterine receptivity.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 2","pages":"Pages 141-150"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9529063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.08.001
Olena M. Kocur B.A., Philip Xie B.Sc., Sydney Souness B.Sc., Stephanie Cheung M.Sc., Zev Rosenwaks M.D., Gianpiero D. Palermo M.D., Ph.D.
Objective
To assess the role of evaluating sperm chromatin fragmentation (SCF) as a tool to guide treatment in couples who achieved unexpectedly poor clinical outcomes after intracytoplasmic sperm injection (ICSI).
Design
We identified couples with an unexpectedly suboptimal clinical outcome after ICSI who were then screened for SCF. Consequently, the same couples were counseled to undergo a subsequent ICSI cycle using either ejaculates processed by microfluidic sperm selection (MFSS) or spermatozoa retrieved from the testis, and clinical outcomes were compared between history and treatment cycles. To confirm the sole effect of a compromised male gamete, we compared the ICSI outcome in cycles where male gametes with abnormal SCF were used to inseminate autologous and donor oocytes. Finally, to eliminate an eventual confounding female factor component, we compared the clinical outcome of ICSI cycles using sibling donor oocytes injected with spermatozoa with normal or abnormal SCF.
Setting
Academic reproductive medicine center point of care.
Patient(s)
The patient population consisted of 76 couples with reproductively healthy and relatively young female partners and male partners with compromised semen parameters, but suitable for ICSI. In a subanalysis, we identified 67 couples with abnormal SCF who underwent ICSI cycle(s) with donor oocytes. Furthermore, we identified 29 couples, 12 with normal SCF and 17 with abnormal, uncorrected SCF, and 7 couples with abnormal, corrected SCF vs. a control, who used sibling donor oocytes for their ICSI cycle(s).
Intervention(s)
For couples who resulted in surprisingly low clinical outcomes after ICSI, despite semen parameters adequate for ICSI and a normal female infertility evaluation, a SCF assessment was performed on the semen specimen using the terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine triphosphate nick-end labeling (TUNEL) assay. The couples then underwent a subsequent ICSI cycle with spermatozoa processed by MFSS or surgically retrieved. Moreover, cycles with donor oocytes were used to confirm the sole contribution of the male gamete.
Main Outcome Measure(s)
Clinical outcomes, such as fertilization, embryo implantation, clinical pregnancy, delivery, and pregnancy loss rates were compared between history and treatment cycle(s) using ejaculated spermatozoa selected by MFSS or from a testicular biopsy, taking into consideration the level of SCF. In a subanalysis, we reported the clinical outcomes of 67 patients who used donor oocytes and compared them with cycles where their own oocytes were used. Furthermore, we compared the ICSI clinical outcomes between cycles using sibling donor oocytes injected with low or high SCF with or without sperm intervention aimed at correcting, or alleviating the degree of SCF.
{"title":"Assessing male gamete genome integrity to ameliorate poor assisted reproductive technology clinical outcome","authors":"Olena M. Kocur B.A., Philip Xie B.Sc., Sydney Souness B.Sc., Stephanie Cheung M.Sc., Zev Rosenwaks M.D., Gianpiero D. Palermo M.D., Ph.D.","doi":"10.1016/j.xfss.2022.08.001","DOIUrl":"10.1016/j.xfss.2022.08.001","url":null,"abstract":"<div><h3>Objective</h3><p>To assess the role of evaluating sperm chromatin fragmentation (SCF) as a tool to guide treatment in couples who achieved unexpectedly poor clinical outcomes after intracytoplasmic sperm injection (ICSI).</p></div><div><h3>Design</h3><p>We identified couples with an unexpectedly suboptimal clinical outcome after ICSI who were then screened for SCF. Consequently, the same couples were counseled to undergo a subsequent ICSI cycle using either ejaculates processed by microfluidic sperm selection (MFSS) or spermatozoa retrieved from the testis, and clinical outcomes were compared between history and treatment cycles. To confirm the sole effect of a compromised male gamete, we compared the ICSI outcome in cycles where male gametes with abnormal SCF were used to inseminate autologous and donor oocytes. Finally, to eliminate an eventual confounding female factor component, we compared the clinical outcome of ICSI cycles using sibling donor oocytes injected with spermatozoa with normal or abnormal SCF.</p></div><div><h3>Setting</h3><p>Academic reproductive medicine center point of care.</p></div><div><h3>Patient(s)</h3><p>The patient population consisted of 76 couples with reproductively healthy and relatively young female partners and male partners with compromised semen parameters, but suitable for ICSI. In a subanalysis, we identified 67 couples with abnormal SCF who underwent ICSI cycle(s) with donor oocytes. Furthermore, we identified 29 couples, 12 with normal SCF and 17 with abnormal, uncorrected SCF, and 7 couples with abnormal, corrected SCF vs. a control, who used sibling donor oocytes for their ICSI cycle(s).</p></div><div><h3>Intervention(s)</h3><p>For couples who resulted in surprisingly low clinical outcomes after ICSI, despite semen parameters adequate for ICSI and a normal female infertility evaluation, a SCF assessment was performed on the semen specimen using the terminal deoxynucleotidyl transferase-mediated fluorescein-deoxyuridine triphosphate nick-end labeling (TUNEL) assay. The couples then underwent a subsequent ICSI cycle with spermatozoa processed by MFSS or surgically retrieved. Moreover, cycles with donor oocytes were used to confirm the sole contribution of the male gamete.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Clinical outcomes, such as fertilization, embryo implantation, clinical pregnancy, delivery, and pregnancy loss rates were compared between history and treatment cycle(s) using ejaculated spermatozoa selected by MFSS or from a testicular biopsy, taking into consideration the level of SCF. In a subanalysis, we reported the clinical outcomes of 67 patients who used donor oocytes and compared them with cycles where their own oocytes were used. Furthermore, we compared the ICSI clinical outcomes between cycles using sibling donor oocytes injected with low or high SCF with or without sperm intervention aimed at correcting, or alleviating the degree of SCF.</p></div><div><h3>Result(s)</h3","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 2-10"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.12.001
Colette P. Davis Ph.D. , Nichole A. Garzia Ph.D , Kara Cushing-Haugen M.S. , Kathryn L. Terry Sc.D. , Yu-Han Chiu M.D., Sc.D. , Helena Sandoval-Insausti M.D., Ph.D. , Jorge E. Chavarro M.D., Sc.D. , Stacey A. Missmer Sc.D. , Holly R. Harris Sc.D
Objective
To examine the association between consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound- or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids, with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.
Design
Prospective cohort study. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).
Setting
Not applicable.
Patient(s)
A total of 81,782 premenopausal participants from the Nurses’ Health Study II cohort were followed from 1991 to 2009 for fruit and vegetable analysis, and 49,927 participants were followed from 1999 to 2009 for pesticide residue burden analysis. Their diet was assessed every 4 years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide residues using a validated method based on surveillance data from the US Department of Agriculture.
Intervention(s)
Not applicable.
Main Outcome Measure(s)
Cases of ultrasound- or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires.
Result(s)
From 1991 to 2009, 9,706 incident cases of ultrasound- or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999 to 2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants with the highest intake of total fruits (≥4/day) were 10% less likely to develop uterine fibroids compared with participants who consumed <1/day (95% CI = 0.80–1.01). No associations were observed with any other fruit or vegetable groups. An inverse association was observed between intake of high-pesticide-residue fruits and vegetables and fibroid risk (HR for 5th vs. 1st quintile = 0.87; 95% CI = 0.77–0.99), while no association with low-pesticide-residue fruits and vegetables was observed (HR for 5th vs. 1st quintile = 1.08; 95% CI = 0.95–1.23).
Conclusion(s)
Our findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Furthermore, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides.
目的探讨果蔬食用量及食用果蔬中农药残留与超声或子宫切除证实的肌瘤发病风险的关系。只有少数研究评估了水果和蔬菜摄入与子宫肌瘤的关系，结果不一致。目前还没有研究表明，通过水果和蔬菜接触农药会有患肌瘤的风险。前瞻性队列研究。采用Cox比例风险模型计算风险比(hr)和95%置信区间(ci)。患者:从1991年到2009年，共有81782名来自护士健康研究II队列的绝经前参与者进行了水果和蔬菜分析，从1999年到2009年，共有49927名参与者进行了农药残留负担分析。他们的饮食每4年通过食物频率问卷进行评估。使用基于美国农业部监测数据的有效方法将水果和蔬菜分为农药残留高或低。干预措施不适用。结果1991年至2009年报告了9706例经超声或子宫切除术确诊的肌瘤病例，1999年至2009年报告了4195例经超声或子宫切除术确诊的肌瘤病例。没有观察到总水果和蔬菜摄入量与子宫肌瘤风险之间的关联。总水果摄入量最高(≥4个/天)的参与者患子宫肌瘤的可能性比每天摄入1个的参与者低10% (95% CI = 0.80-1.01)。没有观察到与任何其他水果或蔬菜组的关联。高农药残留水果和蔬菜的摄入量与肌瘤风险呈负相关(第5五分位数vs第1五分位数的风险比= 0.87;95% CI = 0.77-0.99)，而与低农药残留水果和蔬菜没有关联(第5五分位数vs第1五分位数的HR = 1.08;结论:蔬果中农药残留与子宫肌瘤的发生风险无关。此外，我们的研究结果表明，摄入水果可能与子宫肌瘤的风险较低有关。未来该领域的研究应侧重于整个生命过程中的饮食暴露以及对特定类别农药的评估。
{"title":"Fruit and vegetable consumption, pesticide residue intake from consumption of fruits and vegetables, and risk of uterine fibroids","authors":"Colette P. Davis Ph.D. , Nichole A. Garzia Ph.D , Kara Cushing-Haugen M.S. , Kathryn L. Terry Sc.D. , Yu-Han Chiu M.D., Sc.D. , Helena Sandoval-Insausti M.D., Ph.D. , Jorge E. Chavarro M.D., Sc.D. , Stacey A. Missmer Sc.D. , Holly R. Harris Sc.D","doi":"10.1016/j.xfss.2022.12.001","DOIUrl":"10.1016/j.xfss.2022.12.001","url":null,"abstract":"<div><h3>Objective</h3><p><span>To examine the association between consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound- or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with </span>uterine fibroids, with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.</p></div><div><h3>Design</h3><p><span>Prospective cohort study. Cox </span>proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).</p></div><div><h3>Setting</h3><p>Not applicable.</p></div><div><h3>Patient(s)</h3><p>A total of 81,782 premenopausal participants from the Nurses’ Health Study II cohort were followed from 1991 to 2009 for fruit and vegetable analysis, and 49,927 participants were followed from 1999 to 2009 for pesticide residue burden analysis. Their diet was assessed every 4 years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide residues using a validated method based on surveillance data from the US Department of Agriculture.</p></div><div><h3>Intervention(s)</h3><p>Not applicable.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Cases of ultrasound- or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires.</p></div><div><h3>Result(s)</h3><p>From 1991 to 2009, 9,706 incident cases of ultrasound- or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999 to 2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants with the highest intake of total fruits (≥4/day) were 10% less likely to develop uterine fibroids compared with participants who consumed <1/day (95% CI = 0.80–1.01). No associations were observed with any other fruit or vegetable groups. An inverse association was observed between intake of high-pesticide-residue fruits and vegetables and fibroid risk (HR for 5<sup>th</sup> vs. 1<sup>st</sup> quintile = 0.87; 95% CI = 0.77–0.99), while no association with low-pesticide-residue fruits and vegetables was observed (HR for 5<sup>th</sup> vs. 1<sup>st</sup> quintile = 1.08; 95% CI = 0.95–1.23).</p></div><div><h3>Conclusion(s)</h3><p>Our findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Furthermore, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 90-99"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9983709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9375389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.09.004
Fahad T. Alotaibi Ph.D. , Sadaf Sediqi B.Sc., Christian Klausen Ph.D., Mohamed A. Bedaiwy M.D., Ph.D., Paul J. Yong M.D., Ph.D.
Objective
To study the role of interleukin (IL)-1β and the plasminogen activating (PA) system members in endometriotic stromal cell (ESC) migration/invasion.
Design
Primary cultures of ESCs.
Setting
Tertiary referral center for endometriosis and pelvic pain.
Patient(s)
Patients with surgically excised endometriosis.
Intervention(s)
Interleukin-1β stimulation of primary cultures of ESCs and knockdown of the PA system members urokinase plasminogen activator (uPA), uPA receptor, and plasminogen activator inhibitor-1 (PAI-1).
Main Outcome Measure(s)
Invasion/migration assays.
Result(s)
In primary cultures, IL-1β–stimulated ESC production of the PA system members uPA, uPA receptor, and PAI-1. Interleukin-1β also enhanced ESC migration and invasion, and these effects were inhibited by the IL-1 receptor-1 antagonist anakinra. Knockdown of each of the 3 PA system members also inhibited ESC migration and invasion. Knockdown of these PA system members further attenuated the impact of IL-1β on migration and invasion, suggesting that they mediated the promigration and proinvasion effects of IL-1β. To supplement the cell culture work, immunohistochemistry was performed on tissue sections of endometriotic epithelium/stroma: uPA, PAI-1, and IL-1β histoscores were not found to be correlated with each other.
Conclusion(s)
In primary cultures of ESCs, IL-1β induces migration and invasion, which is mediated by PA system members and inhibited by the drug anakinra. However, the immunohistochemistry expression of IL-1β, urokinase plasminogen inhibitor-1, and PAI-1 were not correlated, suggesting other regulatory mechanisms for PA system members. Inhibition of IL-1β (e.g., with anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.
{"title":"Interleukin-1β and plasminogen activating system members in endometriotic stromal cell migration/invasion","authors":"Fahad T. Alotaibi Ph.D. , Sadaf Sediqi B.Sc., Christian Klausen Ph.D., Mohamed A. Bedaiwy M.D., Ph.D., Paul J. Yong M.D., Ph.D.","doi":"10.1016/j.xfss.2022.09.004","DOIUrl":"10.1016/j.xfss.2022.09.004","url":null,"abstract":"<div><h3>Objective</h3><p>To study the role of interleukin (IL)-1β and the plasminogen<span> activating (PA) system members in endometriotic stromal cell (ESC) migration/invasion.</span></p></div><div><h3>Design</h3><p>Primary cultures of ESCs.</p></div><div><h3>Setting</h3><p>Tertiary referral center for endometriosis<span> and pelvic pain.</span></p></div><div><h3>Patient(s)</h3><p>Patients with surgically excised endometriosis.</p></div><div><h3>Intervention(s)</h3><p>Interleukin-1β stimulation of primary cultures of ESCs and knockdown of the PA system members urokinase plasminogen activator<span> (uPA), uPA receptor, and plasminogen activator inhibitor-1 (PAI-1).</span></p></div><div><h3>Main Outcome Measure(s)</h3><p>Invasion/migration assays.</p></div><div><h3>Result(s)</h3><p>In primary cultures, IL-1β–stimulated ESC production of the PA system members uPA, uPA receptor, and PAI-1. Interleukin-1β also enhanced ESC migration and invasion, and these effects were inhibited by the IL-1 receptor-1 antagonist anakinra<span>. Knockdown of each of the 3 PA system members also inhibited ESC migration and invasion. Knockdown of these PA system members further attenuated the impact of IL-1β on migration and invasion, suggesting that they mediated the promigration and proinvasion effects of IL-1β. To supplement the cell culture work, immunohistochemistry was performed on tissue sections of endometriotic epithelium/stroma: uPA, PAI-1, and IL-1β histoscores were not found to be correlated with each other.</span></p></div><div><h3>Conclusion(s)</h3><p>In primary cultures of ESCs, IL-1β induces migration and invasion, which is mediated by PA system members and inhibited by the drug<span> anakinra. However, the immunohistochemistry expression of IL-1β, urokinase plasminogen inhibitor-1, and PAI-1 were not correlated, suggesting other regulatory mechanisms for PA system members. Inhibition of IL-1β (e.g., with anakinra) may have potential as a novel treatment approach for the migration/invasion of endometriosis.</span></p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 47-55"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10814640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.10.003
Ana Carolina Japur de Sá Rosa-e-Silva M.D. , Ramanaiah Mamillapalli Ph.D. , Julio Cesar Rosa-e-Silva M.D. , Abdullah Ucar M.D. , Joshua Schwartz B.A. , Hugh S. Taylor M.D.
Objective
To study the effect of intrauterine injection of C-X-C motif chemokine ligand 12 (CXCL12), also known as a stem cell chemoattractant (stromal cell-derived factor 1), on fertility and endometrial receptivity in mice with endometriosis.
Design
Laboratory study.
Setting
Academic Medical Center.
Animal(s)
Fifty-six mice underwent chemotherapy and bone marrow transplantation. Thirty-six of these mice underwent either surgery to induce endometriosis (n = 20) or sham surgery (n = 16).
Intervention(s)
Injection of CXCL12 as a potential therapeutic agent to improve fertility in endometriosis.
Main Outcome Measure(s)
Pregnancy rate, bone marrow–derived cell (BMDC) recruitment and endometrial receptivity markers.
Result(s)
The mice with or without endometriosis received a single uterine injection of either CXCL12 or placebo. Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. Mice were euthanized after delivery, and implantation markers homeobox A11, alpha-v beta-3 integrin, and progesterone receptor were analyzed by immunohistochemistry, whereas green fluorescent protein positive BMDC recruitment was quantified by immunohistochemistry and immunofluorescence. The sham surgery groups without endometriosis had the highest cumulative pregnancy rate (100%) regardless of CXCL12 treatment. The endometriosis group treated with placebo had the lowest pregnancy rate. An increased pregnancy rate was noted in the endometriosis group after treatment with CXCL12. There was also an increase in BMDC recruitment and endometrial expression of progesterone receptor and alpha-v beta-3 integrin in the endometriosis group that received CXCL12 compared with that in the endometriosis group that received placebo.
Conclusion(s)
Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. These results suggest that CXCL12 has a potential role as a therapeutic agent in women with infertility related to endometriosis and potentially other endometrial receptivity defects.
{"title":"Uterine administration of C-X-C motif chemokine ligand 12 increases the pregnancy rates in mice with induced endometriosis","authors":"Ana Carolina Japur de Sá Rosa-e-Silva M.D. , Ramanaiah Mamillapalli Ph.D. , Julio Cesar Rosa-e-Silva M.D. , Abdullah Ucar M.D. , Joshua Schwartz B.A. , Hugh S. Taylor M.D.","doi":"10.1016/j.xfss.2022.10.003","DOIUrl":"10.1016/j.xfss.2022.10.003","url":null,"abstract":"<div><h3>Objective</h3><p><span><span><span>To study the effect of intrauterine injection of C-X-C motif </span>chemokine ligand 12 (CXCL12), also known as a stem cell </span>chemoattractant (stromal cell-derived factor 1), on fertility and endometrial receptivity in mice with </span>endometriosis.</p></div><div><h3>Design</h3><p>Laboratory study.</p></div><div><h3>Setting</h3><p>Academic Medical Center.</p></div><div><h3>Animal(s)</h3><p>Fifty-six mice underwent chemotherapy and bone marrow transplantation. Thirty-six of these mice underwent either surgery to induce endometriosis (n = 20) or sham surgery (n = 16).</p></div><div><h3>Intervention(s)</h3><p>Injection of CXCL12 as a potential therapeutic agent to improve fertility in endometriosis.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Pregnancy rate, bone marrow–derived cell (BMDC) recruitment and endometrial receptivity markers.</p></div><div><h3>Result(s)</h3><p><span>The mice with or without endometriosis received a single uterine injection of either CXCL12 or placebo. Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. Mice were euthanized after delivery, and implantation markers homeobox A11, alpha-v beta-3 integrin, and </span>progesterone receptor<span><span> were analyzed by immunohistochemistry<span>, whereas green fluorescent protein positive BMDC recruitment was quantified by immunohistochemistry and </span></span>immunofluorescence<span>. The sham surgery groups without endometriosis had the highest cumulative pregnancy rate (100%) regardless of CXCL12 treatment. The endometriosis group treated with placebo had the lowest pregnancy rate. An increased pregnancy rate was noted in the endometriosis group after treatment with CXCL12. There was also an increase in BMDC recruitment and endometrial expression of progesterone receptor and alpha-v beta-3 integrin in the endometriosis group that received CXCL12 compared with that in the endometriosis group that received placebo.</span></span></p></div><div><h3>Conclusion(s)</h3><p>Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. These results suggest that CXCL12 has a potential role as a therapeutic agent in women with infertility related to endometriosis and potentially other endometrial receptivity defects.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 65-73"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10814658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.10.002
Amr O. Abdelkareem M.B.B.Ch., M.D. , Sahar M. Gebril M.D. , Faten F. AbdelHafez M.D. , Jefferson Terry M.D., Ph.D. , Mohamed A. Bedaiwy M.D., Ph.D.
Objective
To study choriodecidual immunoreactivity of kisspeptin (KISS1) and its receptor (KISS1R) in recurrent pregnancy loss (RPL) due to aneuploidy (AnE) and unexplained (UE) RPL in comparison to control elective abortions (EAbs).
Design
This is a case-control study.
Setting
Tertiary care facility and affiliated research institute.
Patient(s)
Patients with either UE RPL (n = 10) or RPL due to AnE (n = 10) vs. a control group of patients who underwent EAb (n = 10).
Intervention(s)
Immunohistochemistry of archived choriodecidual tissue samples.
Main Outcome Measure(s)
Histoscores of KISS1 and KISS1R immunoreactivity in the syncytiotrophoblast (SyT), cytotrophoblast (CyT), decidual glands (DeGs), and decidual stroma (DeS) across the 3 study groups.
Result(s)
There was no difference in both maternal and gestational ages among the 3 groups. Kisspeptin immunoreactivity was similar in the SyT, CyT, DeGs, and DeS of all groups. Similarly, KISS1R expression was not different in the DeGs or DeS among all study groups. In addition, there was no difference in KISS1R immunoreactivity in the SyTs and CyTs between patients with RPL due to AnE and those with UE RPL. However, KISS1R was significantly lower in the SyT and CyT of patients with RPL due to AnE and UE RPL than in those who underwent EAb.
Conclusion(s)
The expression of KISS1R is lower in the chorionic tissues of euploid (unexplained) and aneuploid RPLs than in the control group. The current results broaden our understanding of the role played by KISS1 and KISS1R in early placentation. Further investigation is necessary to determine whether KISS1 activity is the cause or a sequel of defective placentation.
{"title":"Kisspeptin and kisspeptin receptor immunoreactivity in euploid and aneuploid choriodecidual tissues of recurrent pregnancy losses","authors":"Amr O. Abdelkareem M.B.B.Ch., M.D. , Sahar M. Gebril M.D. , Faten F. AbdelHafez M.D. , Jefferson Terry M.D., Ph.D. , Mohamed A. Bedaiwy M.D., Ph.D.","doi":"10.1016/j.xfss.2022.10.002","DOIUrl":"10.1016/j.xfss.2022.10.002","url":null,"abstract":"<div><h3>Objective</h3><p><span>To study choriodecidual immunoreactivity<span> of kisspeptin<span> (KISS1) and its receptor (KISS1R) in recurrent pregnancy loss (RPL) due to </span></span></span>aneuploidy<span> (AnE) and unexplained (UE) RPL in comparison to control elective abortions (EAbs).</span></p></div><div><h3>Design</h3><p>This is a case-control study.</p></div><div><h3>Setting</h3><p>Tertiary care facility and affiliated research institute.</p></div><div><h3>Patient(s)</h3><p>Patients with either UE RPL (n = 10) or RPL due to AnE (n = 10) vs. a control group of patients who underwent EAb (n = 10).</p></div><div><h3>Intervention(s)</h3><p>Immunohistochemistry of archived choriodecidual tissue samples.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Histoscores of KISS1 and KISS1R immunoreactivity in the syncytiotrophoblast<span><span> (SyT), cytotrophoblast (CyT), decidual glands (DeGs), and decidual </span>stroma (DeS) across the 3 study groups.</span></p></div><div><h3>Result(s)</h3><p>There was no difference in both maternal and gestational ages among the 3 groups. Kisspeptin immunoreactivity was similar in the SyT, CyT, DeGs, and DeS of all groups. Similarly, KISS1R expression was not different in the DeGs or DeS among all study groups. In addition, there was no difference in KISS1R immunoreactivity in the SyTs and CyTs between patients with RPL due to AnE and those with UE RPL. However, KISS1R was significantly lower in the SyT and CyT of patients with RPL due to AnE and UE RPL than in those who underwent EAb.</p></div><div><h3>Conclusion(s)</h3><p>The expression of KISS1R is lower in the chorionic tissues<span> of euploid (unexplained) and aneuploid RPLs than in the control group. The current results broaden our understanding of the role played by KISS1 and KISS1R in early placentation. Further investigation is necessary to determine whether KISS1 activity is the cause or a sequel of defective placentation.</span></p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 56-64"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.xfss.2022.09.003
Chee Wai Ku M.D. , Lay See Ong M.D., Ph.D. , Jody Paige Goh M.B.B.S. , John Allen Ph.D. , Louise Wenyi Low B.Sc. , Jieliang Zhou M.Sc. , Thiam Chye Tan M.B.B.S. , Yie Hou Lee Ph.D.
Objective
To study differences in cytokine expression profiles between women with ongoing pregnancy and those experiencing spontaneous miscarriage, among women who presented with threatened miscarriage before week 16 of gestation.
Design
Prospective cohort study.
Setting
Academic hospital.
Patient(s)
In this prospective cohort study, 155 pregnant women, comprising normal pregnant women recruited from antenatal clinics (n = 97) and women with threatened miscarriage recruited from an emergency walk-in clinic (n = 58).
Intervention(s)
None.
Main Outcome Measure(s)
Sixty-five serum cytokines quantified using multiplex immunoassay correlated with miscarriage outcomes.
Result(s)
Among women presenting with threatened miscarriage, those who eventually miscarried had significantly lower levels of interleukin (IL)-2, IL-12p70, IL-17A, B-cell–activating factor, B lymphocyte chemoattractant, basic nerve growth factor, interferon-γ, tumor necrosis factor–related apoptosis-inducing ligand, thymic stromal lymphopoietin, and tumor necrosis factor-α and higher levels of vascular endothelial growth factor A, IL-21, and stromal cell–derived factor 1α than those with ongoing pregnancy. Comparisons between normal pregnancies and women with threatened miscarriage who eventually miscarried revealed significant differences across 7 cytokines: B-cell–activating factor; B lymphocyte chemoattractant; basic nerve growth factor; IL-17A; fractalkine/CX3CL1; vascular endothelial growth factor A; and CCL22. Vascular endothelial growth factor A exhibited a negative correlation with the progesterone level (r = −0.270). The cluster of significant cytokines alludes to T cell proliferation, B-cell proliferation, natural killer cell–mediated cytotoxicity, and apoptosis as important pathways that determine pregnancy outcomes. Bioinformatic analysis further revealed alteration of the suppressor of cytokine signaling proteins family of Janus kinase-signal transducer and activator of transcription signaling axis by cytokines as a plausible key molecular mechanism in spontaneous miscarriage.
Conclusion(s)
This study demonstrates that the regulated balance between the proinflammatory and anti-inflammatory pathways is crucial to maintaining pregnancy. A better understanding of the cytokines associated with immunomodulatory effects may lead to novel targets for the prediction and treatment of spontaneous miscarriage.
{"title":"Defects in protective cytokine profiles in spontaneous miscarriage in the first trimester","authors":"Chee Wai Ku M.D. , Lay See Ong M.D., Ph.D. , Jody Paige Goh M.B.B.S. , John Allen Ph.D. , Louise Wenyi Low B.Sc. , Jieliang Zhou M.Sc. , Thiam Chye Tan M.B.B.S. , Yie Hou Lee Ph.D.","doi":"10.1016/j.xfss.2022.09.003","DOIUrl":"10.1016/j.xfss.2022.09.003","url":null,"abstract":"<div><h3>Objective</h3><p>To study differences in cytokine expression profiles between women with ongoing pregnancy and those experiencing spontaneous miscarriage, among women who presented with threatened miscarriage before week 16 of gestation.</p></div><div><h3>Design</h3><p>Prospective cohort study.</p></div><div><h3>Setting</h3><p>Academic hospital.</p></div><div><h3>Patient(s)</h3><p>In this prospective cohort study, 155 pregnant women, comprising normal pregnant women recruited from antenatal clinics (n = 97) and women with threatened miscarriage recruited from an emergency walk-in clinic (n = 58).</p></div><div><h3>Intervention(s)</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Sixty-five serum cytokines quantified using multiplex immunoassay correlated with miscarriage outcomes.</p></div><div><h3>Result(s)</h3><p>Among women presenting with threatened miscarriage, those who eventually miscarried had significantly lower levels of interleukin (IL)-2, IL-12p70, IL-17A, B-cell–activating factor, B lymphocyte chemoattractant, basic nerve growth factor, interferon-γ, tumor necrosis factor–related apoptosis-inducing ligand, thymic stromal lymphopoietin, and tumor necrosis factor-α and higher levels of vascular endothelial growth factor A, IL-21, and stromal cell–derived factor 1α than those with ongoing pregnancy. Comparisons between normal pregnancies and women with threatened miscarriage who eventually miscarried revealed significant differences across 7 cytokines: B-cell–activating factor; B lymphocyte chemoattractant; basic nerve growth factor; IL-17A; fractalkine/CX3CL1; vascular endothelial growth factor A; and CCL22. Vascular endothelial growth factor A exhibited a negative correlation with the progesterone level (r <em>=</em> −0.270). The cluster of significant cytokines alludes to T cell proliferation, B-cell proliferation, natural killer cell–mediated cytotoxicity, and apoptosis as important pathways that determine pregnancy outcomes. Bioinformatic analysis further revealed alteration of the suppressor of cytokine signaling proteins family of Janus kinase-signal transducer and activator of transcription signaling axis by cytokines as a plausible key molecular mechanism in spontaneous miscarriage.</p></div><div><h3>Conclusion(s)</h3><p>This study demonstrates that the regulated balance between the proinflammatory and anti-inflammatory pathways is crucial to maintaining pregnancy. A better understanding of the cytokines associated with immunomodulatory effects may lead to novel targets for the prediction and treatment of spontaneous miscarriage.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 36-46"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10814627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate whether blastocysts that divide irregularly reduce subsequent blastocyst euploidy.
Design
Retrospective study.
Setting
Private clinic.
Patient(s)
A total of 122 blastocysts for which consent for disposal and research use was obtained.
Intervention(s)
None.
Main Outcome Measure(s)
Results of next-generation sequencing analysis of the blastocysts and whether blastomeres by normal or irregular divisions subsequently participated in blastocyst formation or not.
Result(s)
The embryos were classified according to their dynamics until the second cleavage. The blastocyst euploidy rates were 33.3% (19/57) in the normal cleavage (NC) group, 38.3% (18/47) in the direct cleavage (embryos with one cell dividing into 3 cells) (DC) group, and 72.2% (13/18) in the reverse cleavage (RC) (embryos with fused cells once divided) group. The rate of the RC group was significantly higher than that of the NC group.
The blastocyst participation rate of the blastomeres were 95.6% in the NC group and 56.5% in that derived from DC of the first cleavage, and 91.7% in that of blastomeres derived from normal division of the second cleavage and 53.6% in that derived from DC of the second cleavage, both of which were significantly lower in the latter. In the RC group, the rates of fused and nonfused blastomeres were 62.1% and 87.5%, respectively, with no significant difference.
Conclusion(s)
The blastomeres generated by DC were often excluded from blastocyst formation, and we speculate that this is one reason why their division does not reduce blastocyst euploidy. The association between RC and euploidy of blastocysts merits further study.
{"title":"The effect of early irregular cell division of human embryos on blastocyst euploidy: considerations from the subsequent development of the blastomeres by direct or reverse cleavage","authors":"Shinichi Watanabe B.V.Sc. , Kaori Yoshikai M.S. , Yukino Matsuda B.S. , Shunsuke Miyai Ph.D. , Yuki Sawada M.D., Ph.D. , Hiroki Kurahashi M.D., Ph.D. , Tomio Sawada M.D., Ph.D.","doi":"10.1016/j.xfss.2022.11.001","DOIUrl":"10.1016/j.xfss.2022.11.001","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate whether blastocysts that divide irregularly reduce subsequent blastocyst euploidy.</p></div><div><h3>Design</h3><p>Retrospective study.</p></div><div><h3>Setting</h3><p>Private clinic.</p></div><div><h3>Patient(s)</h3><p>A total of 122 blastocysts for which consent for disposal and research use was obtained.</p></div><div><h3>Intervention(s)</h3><p>None.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Results of next-generation sequencing analysis of the blastocysts and whether blastomeres by normal or irregular divisions subsequently participated in blastocyst formation or not.</p></div><div><h3>Result(s)</h3><p>The embryos were classified according to their dynamics until the second cleavage. The blastocyst euploidy rates were 33.3% (19/57) in the normal cleavage (NC) group, 38.3% (18/47) in the direct cleavage (embryos with one cell dividing into 3 cells) (DC) group, and 72.2% (13/18) in the reverse cleavage (RC) (embryos with fused cells once divided) group. The rate of the RC group was significantly higher than that of the NC group.</p><p>The blastocyst participation rate of the blastomeres were 95.6% in the NC group and 56.5% in that derived from DC of the first cleavage, and 91.7% in that of blastomeres derived from normal division of the second cleavage and 53.6% in that derived from DC of the second cleavage, both of which were significantly lower in the latter. In the RC group, the rates of fused and nonfused blastomeres were 62.1% and 87.5%, respectively, with no significant difference.</p></div><div><h3>Conclusion(s)</h3><p>The blastomeres generated by DC were often excluded from blastocyst formation, and we speculate that this is one reason why their division does not reduce blastocyst euploidy. The association between RC and euploidy of blastocysts merits further study.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":"4 1","pages":"Pages 21-29"},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9376464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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