Pub Date : 2024-02-01DOI: 10.1016/j.xfss.2023.11.005
Joy Britten M.D. , Jaime A. Roura-Monllor M.D., M.S. , Minnie Malik Ph.D. , Sean Moran Ph.D. , Anthony DeAngelis M.D., Ph.D. , Paul Driggers Ph.D. , Sadia Afrin Ph.D. , Mostafa Borahay M.D., Ph.D. , William H. Catherino M.D., Ph.D.
Objectives
To assess the effect of simvastatin on uterine leiomyoma growth and extracellular matrix (ECM) deposition.
Design
Laboratory analysis of human leiomyoma cell culture, xenograft in a mouse model, and patient tissue from a clinical trial.
Setting
Academic research center.
Patient(s)
Tissue culture from human leiomyoma tissue and surgical leiomyoma tissue sections from a placebo-controlled randomized clinical trial.
Intervention(s)
Simvastatin treatment.
Main Outcome Measure(s)
Serum concentrations, xenograft volumes, and protein expression.
Results
Mice xenografted with 3-dimensional human leiomyoma cultures were divided as follows: 7 untreated controls; 12 treated with activated simvastatin at 10 mg/kg body weight; and 15 at 20 mg/kg body weight. Simvastatin was detected in the serum of mice injected at the highest dose. Xenograft volumes were significantly smaller (mean 53% smaller at the highest concentration). There was dissolution of compact ECM, decreased ECM formation, and lower collagen protein expression in xenografts. Membrane type 1 matrix metalloproteinase was increased in vitro and in vivo. Matrix metalloproteinase 2 and low-density lipoprotein receptor-related protein 1 were increased in vitro.
Conclusions
Simvastatin exhibited antitumoral activity with ECM degradation and decreased leiomyoma tumor volume in vivo. Activation of the matrix metalloproteinase 2, membrane type 1 matrix metalloproteinase, and low-density lipoprotein receptor-related protein 1 pathway may explain these findings.
{"title":"Simvastatin induces degradation of the extracellular matrix in human leiomyomata: novel in vitro, in vivo, and patient level evidence of matrix metalloproteinase involvement","authors":"Joy Britten M.D. , Jaime A. Roura-Monllor M.D., M.S. , Minnie Malik Ph.D. , Sean Moran Ph.D. , Anthony DeAngelis M.D., Ph.D. , Paul Driggers Ph.D. , Sadia Afrin Ph.D. , Mostafa Borahay M.D., Ph.D. , William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2023.11.005","DOIUrl":"10.1016/j.xfss.2023.11.005","url":null,"abstract":"<div><h3>Objectives</h3><p>To assess the effect of simvastatin<span> on uterine leiomyoma<span> growth and extracellular matrix (ECM) deposition.</span></span></p></div><div><h3>Design</h3><p><span>Laboratory analysis of human leiomyoma<span> cell culture, xenograft in a mouse model, and patient tissue from a </span></span>clinical trial.</p></div><div><h3>Setting</h3><p>Academic research center.</p></div><div><h3>Patient(s)</h3><p>Tissue culture from human leiomyoma tissue and surgical leiomyoma tissue sections from a placebo-controlled randomized clinical trial.</p></div><div><h3>Intervention(s)</h3><p>Simvastatin treatment.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Serum concentrations, xenograft volumes, and protein expression.</p></div><div><h3>Results</h3><p><span>Mice xenografted with 3-dimensional human leiomyoma cultures were divided as follows: 7 untreated controls; 12 treated with activated simvastatin at 10 mg/kg body weight; and 15 at 20 mg/kg body weight. Simvastatin was detected in the serum of mice injected at the highest dose. Xenograft volumes were significantly smaller (mean 53% smaller at the highest concentration). There was dissolution of compact ECM, decreased ECM formation, and lower collagen protein expression in xenografts. </span>Membrane type 1 matrix metalloproteinase<span> was increased in vitro and in vivo. Matrix metalloproteinase 2 and low-density lipoprotein receptor-related protein 1 were increased in vitro.</span></p></div><div><h3>Conclusions</h3><p>Simvastatin exhibited antitumoral activity with ECM degradation and decreased leiomyoma tumor volume in vivo. Activation of the matrix metalloproteinase 2, membrane type 1 matrix metalloproteinase, and low-density lipoprotein receptor-related protein 1 pathway may explain these findings.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479718","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 : 2024-02-01DOI: 10.1016/j.xfss.2023.12.001
Daniela Paes de Almeida Ferreira Braga D.V.M., Ph.D. , Amanda Setti M.Sc. , Edward Carrilho M.D. , Patrícia Guilherme M.Sc. , Assumpto Iaconelli Jr. M.D. , Edson Borges Jr. M.D., Ph.D.
Objective
To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles.
Design
Cohort study.
Setting
Private university–affiliated in vitro fertilization center.
Patient(s)
This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups.
Intervention(s)
The kinetic recorded markers were time to pronuclear appearance and fading, time to 2–8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups.
Main Outcome Measure(s)
Embryo morphokinetics and clinical outcomes.
Results
Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively.
Conclusions
Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.
{"title":"Progesterone-primed cycles result in slower embryos without compromising implantation potential and with the advantages of oral administration and potential cost reduction","authors":"Daniela Paes de Almeida Ferreira Braga D.V.M., Ph.D. , Amanda Setti M.Sc. , Edward Carrilho M.D. , Patrícia Guilherme M.Sc. , Assumpto Iaconelli Jr. M.D. , Edson Borges Jr. M.D., Ph.D.","doi":"10.1016/j.xfss.2023.12.001","DOIUrl":"10.1016/j.xfss.2023.12.001","url":null,"abstract":"<div><h3>Objective</h3><p>To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles.</p></div><div><h3>Design</h3><p>Cohort study.</p></div><div><h3>Setting</h3><p>Private university–affiliated in vitro fertilization center.</p></div><div><h3>Patient(s)</h3><p>This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups.</p></div><div><h3>Intervention(s)</h3><p>The kinetic recorded markers were time to pronuclear appearance and fading, time to 2–8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Embryo morphokinetics and clinical outcomes.</p></div><div><h3>Results</h3><p>Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively.</p></div><div><h3>Conclusions</h3><p>Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138621879","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.09.004
Tao Bai Ph.D. , Mohamed Ali Ph.D. , Bernard Somers B.S. , Qiwei Yang Ph.D. , Sue McKinney J.D. , Ayman Al-Hendy M.D., Ph.D.
Objective
To investigate the combined effects of Crila and green tea extract, epigallocatechin gallate (EGCG), compared with single treatments, on human uterine fibroid cells.
Design
Human uterine leiomyoma (HuLM) cells were treated with different concentrations of Crila, alone or in combination with EGCG, and several experiments were employed.
Setting
A laboratory study.
Patientss
N/A.
Interventions
Crila, EGCG.
Main Outcome Measures
Cell proliferation assay, drug synergy using combination index, protein and gene expression analysis of proliferation marker proliferating cell nuclear antigen, and apoptosis marker BAX using western blotting and quantitative polymerase chain reaction, respectively.
Results
Results showed that tested Crila concentrations, when combined with 25 and 50 μM EGCG, exerted synergistic growth inhibitory effects on HuLM viability. This inhibitory effect on HuLM cell viability was because of decreased cell proliferation, as shown by a decrease in the proliferation marker proliferating cell nuclear antigen at messenger RNA and protein levels, rather than inducing apoptosis.
Conclusion
Our study concludes that the utility of natural compounds may provide a safe and cost-effective alternative to currently used short-term hormonal therapies against uterine fibroids.
{"title":"The combination of natural compounds Crila and epigallocatechin gallate showed enhanced antiproliferative effects on human uterine fibroid cells compared with single treatments","authors":"Tao Bai Ph.D. , Mohamed Ali Ph.D. , Bernard Somers B.S. , Qiwei Yang Ph.D. , Sue McKinney J.D. , Ayman Al-Hendy M.D., Ph.D.","doi":"10.1016/j.xfss.2023.09.004","DOIUrl":"10.1016/j.xfss.2023.09.004","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the combined effects of Crila and green tea extract, epigallocatechin gallate (EGCG), compared with single treatments, on human uterine fibroid cells.</p></div><div><h3>Design</h3><p>Human uterine leiomyoma (HuLM) cells were treated with different concentrations of Crila, alone or in combination with EGCG, and several experiments were employed.</p></div><div><h3>Setting</h3><p>A laboratory study.</p></div><div><h3>Patientss</h3><p>N/A.</p></div><div><h3>Interventions</h3><p>Crila, EGCG.</p></div><div><h3>Main Outcome Measures</h3><p>Cell proliferation assay, drug synergy using combination index, protein and gene expression analysis of proliferation marker proliferating cell nuclear antigen, and apoptosis marker BAX using western blotting and quantitative polymerase chain reaction, respectively.</p></div><div><h3>Results</h3><p>Results showed that tested Crila concentrations, when combined with 25 and 50 μM EGCG, exerted synergistic growth inhibitory effects on HuLM viability. This inhibitory effect on HuLM cell viability was because of decreased cell proliferation, as shown by a decrease in the proliferation marker proliferating cell nuclear antigen at messenger RNA and protein levels, rather than inducing apoptosis.</p></div><div><h3>Conclusion</h3><p>Our study concludes that the utility of natural compounds may provide a safe and cost-effective alternative to currently used short-term hormonal therapies against uterine fibroids.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666335X23000526/pdfft?md5=16ad7e27860baaa5dca2d9ad106e25e0&pid=1-s2.0-S2666335X23000526-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175902","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}
To investigate the structural bases of human oocytes’ cytoplasmic abnormalities and the causative mechanism of their emergence. Knowledge of an abnormal oocyte’s intracellular organization is vital to establishing reliable criteria for clinical evaluation of oocyte morphology.
Design
Laboratory-based study on experimental material provided by a private assisted reproduction clinic.
Setting
University laboratory and imaging center.
Patients
A total of 105 women undergoing hormonal stimulation for in vitro fertilization (IVF) donated their spare oocytes for this study.
Interventions
Transmission electron microscopy (TEM) was used to analyze the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely, refractile bodies; centrally located cytoplasmic granularity (CLCG); smooth endoplasmic reticulum (SER) disc; and vacuoles. A total of 133 immature oocytes were exposed to cytoskeleton-targeting compounds or matured in control conditions, and their morphology was examined using fluorescent and electron microscopy.
Main Outcome Measures
The ultrastructural morphology of dysmorphic oocytes was analyzed. Drug-treated oocytes had their maturation efficiency, chromosome-microtubule configurations, and fine intracellular morphology examined.
Results
TEM revealed ultrastructural characteristics of common oocyte aberrations and indicated that excessive organelle clustering was the underlying cause of 2 of the studied morphotypes. Inhibition experiments showed that disruption of actin, not microtubules, allows for inordinate aggregation of subcellular structures, resembling the ultrastructural pattern seen in morphologically abnormal oocytes retrieved in IVF cycles. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation.
Conclusion
The ultrastructural analogy between dysmorphic oocytes and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes’ inner workings and the origin of morphological abnormalities is a step forward to a more objective oocyte quality assessment in IVF practice.
{"title":"The ultrastructural nature of human oocytes’ cytoplasmic abnormalities and the role of cytoskeleton dysfunction","authors":"Martina Tatíčková M.Sc. , Zuzana Trebichalská M.Sc. , Drahomíra Kyjovská , Pavel Otevřel M.D. , Soňa Kloudová Ph.D. , Zuzana Holubcová Ph.D.","doi":"10.1016/j.xfss.2023.09.002","DOIUrl":"10.1016/j.xfss.2023.09.002","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the structural bases of human oocytes’ cytoplasmic abnormalities and the causative mechanism of their emergence. Knowledge of an abnormal oocyte’s intracellular organization is vital to establishing reliable criteria for clinical evaluation of oocyte morphology.</p></div><div><h3>Design</h3><p>Laboratory-based study on experimental material provided by a private assisted reproduction clinic.</p></div><div><h3>Setting</h3><p>University laboratory and imaging center.</p></div><div><h3>Patients</h3><p>A total of 105 women undergoing hormonal stimulation for in vitro fertilization (IVF) donated their spare oocytes for this study.</p></div><div><h3>Interventions</h3><p>Transmission electron microscopy (TEM) was used to analyze the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely, refractile bodies; centrally located cytoplasmic granularity (CLCG); smooth endoplasmic reticulum (SER) disc; and vacuoles. A total of 133 immature oocytes were exposed to cytoskeleton-targeting compounds or matured in control conditions, and their morphology was examined using fluorescent and electron microscopy.</p></div><div><h3>Main Outcome Measures</h3><p>The ultrastructural morphology of dysmorphic oocytes was analyzed. Drug-treated oocytes had their maturation efficiency, chromosome-microtubule configurations, and fine intracellular morphology examined.</p></div><div><h3>Results</h3><p>TEM revealed ultrastructural characteristics of common oocyte aberrations and indicated that excessive organelle clustering was the underlying cause of 2 of the studied morphotypes. Inhibition experiments showed that disruption of actin, not microtubules, allows for inordinate aggregation of subcellular structures, resembling the ultrastructural pattern seen in morphologically abnormal oocytes retrieved in IVF cycles. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation.</p></div><div><h3>Conclusion</h3><p>The ultrastructural analogy between dysmorphic oocytes and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes’ inner workings and the origin of morphological abnormalities is a step forward to a more objective oocyte quality assessment in IVF practice.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666335X23000502/pdfft?md5=b0edda2eea26adde4bc0763007bf4808&pid=1-s2.0-S2666335X23000502-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143639","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.08.001
Cynthia Dela Cruz Ph.D. , Abigail Wandoff B.S. , Margaret Brunette M.S. , Vasantha Padmanabhan Ph.D. , Ariella Shikanov Ph.D. , Molly B. Moravek M.D., M.P.H.
Objective
To investigate in vitro fertilization (IVF) outcomes in an adolescent transmasculine mouse model mimicking gender-affirming hormone therapy in prepubertal youth, both on testosterone (T) and after T washout.
Design
Experimental laboratory study using a validated mouse model.
Setting
University-based basic science research laboratory.
Animal(s)
A total of 80 prepubertal 26-day-old C57BL/6N female mice were used in this study.
Intervention(s)
Animals (n = 10/group) were implanted subcutaneously with gonadotropin-releasing hormone agonist at 3.6 mg or received sham surgery. After 21 days, they were implanted with silastic tubing containing either T 10 mg or placebo for 6 weeks. After 6 weeks, a group of animals were superovulated for immediate IVF, and another group had the implant removed and went through superovulation for IVF after 2 weeks (washout IVF). The total number of oocytes yielded, oocyte maturity rate, fertilization rate, and numbers of 2-cell embryos, 4–8-cell embryos, morula, blastocysts, and hatching blastocysts were recorded.
Result(s)
Testosterone treatment negatively impacted IVF outcomes in animals stimulated when receiving T, but not after T washout. Pretreatment with gonadotropin-releasing hormone agonist did not affect IVF outcomes.
Conclusion(s)
Although current T had a negative impact on IVF outcomes compared with controls, animals were still able to produce viable oocytes for fertilization and develop into blastocysts. Future efforts to study the impact of long-term T exposure on oocyte quality, especially aneuploidy rates, pregnancy outcomes, and live birth rates, are necessary.
{"title":"In vitro fertilization outcomes in a mouse model of gender-affirming hormone therapy in transmasculine youth","authors":"Cynthia Dela Cruz Ph.D. , Abigail Wandoff B.S. , Margaret Brunette M.S. , Vasantha Padmanabhan Ph.D. , Ariella Shikanov Ph.D. , Molly B. Moravek M.D., M.P.H.","doi":"10.1016/j.xfss.2023.08.001","DOIUrl":"10.1016/j.xfss.2023.08.001","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate in vitro fertilization (IVF) outcomes in an adolescent transmasculine mouse model mimicking gender-affirming hormone therapy in prepubertal youth, both on testosterone (T) and after T washout.</p></div><div><h3>Design</h3><p>Experimental laboratory study using a validated mouse model.</p></div><div><h3>Setting</h3><p>University-based basic science research laboratory.</p></div><div><h3>Animal(s)</h3><p>A total of 80 prepubertal 26-day-old C57BL/6N female mice were used in this study.</p></div><div><h3>Intervention(s)</h3><p><span>Animals (n = 10/group) were implanted subcutaneously with gonadotropin-releasing hormone agonist at 3.6 mg or received sham surgery. After 21 days, they were implanted with silastic tubing containing either T 10 mg or placebo for 6 weeks. After 6 weeks, a group of animals were superovulated for immediate IVF, and another group had the implant removed and went through </span>superovulation<span> for IVF after 2 weeks (washout IVF). The total number of oocytes yielded, oocyte maturity rate, fertilization rate, and numbers of 2-cell embryos, 4–8-cell embryos, morula<span>, blastocysts, and hatching blastocysts were recorded.</span></span></p></div><div><h3>Result(s)</h3><p>Testosterone treatment negatively impacted IVF outcomes in animals stimulated when receiving T, but not after T washout. Pretreatment with gonadotropin-releasing hormone agonist did not affect IVF outcomes.</p></div><div><h3>Conclusion(s)</h3><p>Although current T had a negative impact on IVF outcomes compared with controls, animals were still able to produce viable oocytes for fertilization and develop into blastocysts. Future efforts to study the impact of long-term T exposure on oocyte quality, especially aneuploidy rates, pregnancy outcomes, and live birth rates, are necessary.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10002562","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.09.005
Daniel Nassau M.D. , Nicholas A. Deebel M.D. , Eliyahu Kresch M.D. , Davis Temple B.S. , Shathiyah Kulandavelu Ph.D. , Himanshu Arora Ph.D. , Ranjith Ramasamy M.D.
Objective
To study compensatory changes in testicular growth and the hormonal axis after unilateral orchiectomy in a neonatal, prepubertal, and pubertal/adult murine model. This is the first study to use a neonatal mouse survival surgery model.
Design
A laboratory-based study examining a control, neonatal, prepubertal, and pubertal/adult mouse model.
Setting
University-based basic science research laboratory.
Animals
Control, neonatal (2–4 days of life), prepubertal (12–21 days of life), and pubertal/adult (42–44 days of life) C57BL/6 mouse models.
Intervention
Unilateral orchiectomy in the neonatal, prepubertal, and pubertal/adult mouse models at their respective ages.
Main Outcome Measures
Body and testis weight and testicular length in the long axis were measured in a blinded fashion. In a similar way, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone were assessed.
Results
Testes from neonatal and prepubertal mice weighed more (110.5, 12.2 and 103.0, 7.2 mg, respectively) than the control mice (91, 11.9 mg). There was no difference between the postpubertal group and the control group. The degree of compensatory hypertrophy was greater in the neonatal group but not in the prepubertal group when compared with the postpubertal group. Differences in follicle-stimulating hormone and testosterone were not statistically significant between the experimental and control arms. LH was significantly elevated in all experimental groups compared with the control.
Conclusions
This is the first study to assess testicular compensatory hypertrophy using a neonatal mouse survival surgery model. Testicular hypertrophy occurs when unilateral loss occurs before puberty, but not in adulthood in mice. Earlier testis loss may contribute to a greater degree of growth. Functionally, the unilateral testis can maintain eugonadal testosterone levels, but higher levels of LH are required after hemicastration to sustain eugonadal testosterone levels.
{"title":"Age-dependent effect on contralateral testicular compensation after testicular loss","authors":"Daniel Nassau M.D. , Nicholas A. Deebel M.D. , Eliyahu Kresch M.D. , Davis Temple B.S. , Shathiyah Kulandavelu Ph.D. , Himanshu Arora Ph.D. , Ranjith Ramasamy M.D.","doi":"10.1016/j.xfss.2023.09.005","DOIUrl":"10.1016/j.xfss.2023.09.005","url":null,"abstract":"<div><h3>Objective</h3><p>To study compensatory changes in testicular growth and the hormonal axis after unilateral orchiectomy in a neonatal, prepubertal, and pubertal/adult murine model. This is the first study to use a neonatal mouse survival surgery model.</p></div><div><h3>Design</h3><p>A laboratory-based study examining a control, neonatal, prepubertal, and pubertal/adult mouse model.</p></div><div><h3>Setting</h3><p>University-based basic science research laboratory.</p></div><div><h3>Animals</h3><p>Control, neonatal (2–4 days of life), prepubertal (12–21 days of life), and pubertal/adult (42–44 days of life) C57BL/6 mouse models.</p></div><div><h3>Intervention</h3><p>Unilateral orchiectomy in the neonatal, prepubertal, and pubertal/adult mouse models at their respective ages.</p></div><div><h3>Main Outcome Measures</h3><p><span>Body and testis weight and testicular length in the long axis were measured in a blinded fashion. In a similar way, testosterone, </span>luteinizing hormone (LH), and follicle-stimulating hormone were assessed.</p></div><div><h3>Results</h3><p>Testes from neonatal and prepubertal mice weighed more (110.5, 12.2 and 103.0, 7.2 mg, respectively) than the control mice (91, 11.9 mg). There was no difference between the postpubertal group and the control group. The degree of compensatory hypertrophy was greater in the neonatal group but not in the prepubertal group when compared with the postpubertal group. Differences in follicle-stimulating hormone and testosterone were not statistically significant between the experimental and control arms. LH was significantly elevated in all experimental groups compared with the control.</p></div><div><h3>Conclusions</h3><p>This is the first study to assess testicular compensatory hypertrophy using a neonatal mouse survival surgery model. Testicular hypertrophy occurs when unilateral loss occurs before puberty, but not in adulthood in mice. Earlier testis loss may contribute to a greater degree of growth. Functionally, the unilateral testis can maintain eugonadal testosterone levels, but higher levels of LH are required after hemicastration to sustain eugonadal testosterone levels.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160588","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.10.001
William H. Catherino M.D., Ph.D.
{"title":"From the Editor-in-Chief","authors":"William H. Catherino M.D., Ph.D.","doi":"10.1016/j.xfss.2023.10.001","DOIUrl":"10.1016/j.xfss.2023.10.001","url":null,"abstract":"","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160595","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 determine whether cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells.
Design
A basic science study using primary cultures of patient-matched myometrial and fibroid cells.
Setting
Academic laboratory.
Patient(s)
Premenopausal women undergoing myomectomy or hysterectomy for the treatment of symptomatic uterine fibroids.
Intervention(s)
Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell tension system or static control. Secondarily, inhibition of G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase.
Main Outcome Measure(s)
Cell alignment, cell number, and collagen content.
Result(s)
Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation, and procollagen content between myometrial and fibroid cells. Procollagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. G protein-coupled estrogen receptor-1 inhibition decreases cellular alignment in the presence of strain.
Conclusion(s)
Mechanotransduction affecting cytoskeletal arrangement through the G protein-coupled estrogen receptor-1-phosphatidylinositol 3-kinase pathway is altered in fibroid cells. These results highlight the importance of incorporating mechanical stimulation into the in vitro study of fibroid pathology.
{"title":"Uterine fibroid cell cytoskeletal organization is affected by altered G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase signaling","authors":"Rachel Warwar M.D. , Andreja Moset Zupan B.S. , Carolyn Nietupski B.S. , Maricela Manzanares , Emily G. Hurley M.D. , Stacey C. Schutte Ph.D.","doi":"10.1016/j.xfss.2023.09.007","DOIUrl":"10.1016/j.xfss.2023.09.007","url":null,"abstract":"<div><h3>Objective</h3><p>To determine whether cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells.</p></div><div><h3>Design</h3><p>A basic science study using primary cultures of patient-matched myometrial and fibroid cells.</p></div><div><h3>Setting</h3><p>Academic laboratory.</p></div><div><h3>Patient(s)</h3><p><span><span>Premenopausal women undergoing </span>myomectomy or </span>hysterectomy<span><span> for the treatment of symptomatic </span>uterine fibroids.</span></p></div><div><h3>Intervention(s)</h3><p>Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell tension system or static control. Secondarily, inhibition of G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase.</p></div><div><h3>Main Outcome Measure(s)</h3><p>Cell alignment, cell number, and collagen content.</p></div><div><h3>Result(s)</h3><p>Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation<span>, and procollagen content between myometrial and fibroid cells. Procollagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. G protein-coupled estrogen receptor-1 inhibition decreases cellular alignment in the presence of strain.</span></p></div><div><h3>Conclusion(s)</h3><p><span>Mechanotransduction affecting cytoskeletal arrangement through the G protein-coupled estrogen receptor-1-phosphatidylinositol 3-kinase pathway is altered in fibroid cells. These results highlight the importance of incorporating </span>mechanical stimulation into the in vitro study of fibroid pathology.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41174145","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 : 2023-11-01DOI: 10.1016/j.xfss.2023.07.003
Erica D. Louden M.D. Ph.D. , Michael P. Dougherty M.D. , Lynn P. Chorich M.S. , Ali Eroglu Ph.D., D.V.M. , Lawrence C. Layman M.D.
Objective
To study if a pituitary or ovarian defect contributes to subfertility of the female Nsmf knockout (KO) mouse, an animal model of the hypogonadotropic hypogonadism gene NSMF.
Design
Analysis of hypothalamic, pituitary and ovarian gene expression at baseline, serum gonadotropin levels before and after gonadotropin-releasing hormone (GnRH) stimulation, ovarian response and implantation after superovulation, gonadotropin effects after ovariectomy, and ovarian NSMF protein expression.
Setting
University research laboratory.
Patients
None; mice were used.
Interventions
Gonadotropin-releasing hormone stimulation, superovulation, and ovariectomy in separate experiments.
Main Outcome Measures
Gene expression in the hypothalamus, pituitary, and ovary; ovarian response and implantation after superovulation; serum gonadotropins after GnRH stimulation and ovariectomy; Western blot to measure ovarian NSMF expression.
Results
We found increased hypothalamic Kiss1, Gnrh1, and Jak2 mRNA expression in female Nsmf KO vs. wild type (WT) mice. However, pituitary gonadotropin, and GnRH receptor gene expression was not affected, and serum gonadotropin levels were normal. Gonadotropins increased after ovariectomy for both groups. Baseline Kiss1, Fshr, Prkaca, Prkar1a, and Gdf9 ovarian mRNA expression was increased and Cyp19a1 expression was decreased in Nsmf KO mice, while superovulated Nsmf KO mice had reduced ovarian Kiss1r, Prkar1a, and Fshr mRNA expression, 50% less oocytes, and normal implantation. Western blot demonstrated NSMF protein expression in the ovary of WT mice.
Conclusions
Altered hypothalamic and ovarian gene expression was demonstrated in female Nsmf KO mice. It is possible that increased hypothalamic Gnrh1 and Kiss1 mRNA expression could compensate for reduced NSMF enabling a normal pituitary gonadotropin response. Impaired superovulation response, altered ovarian gene expression, and decreased number of oocytes indicate ovarian dysfunction, but a uterine factor cannot be excluded. These findings provide an anatomic basis for future mechanistic studies of subfertility in female Nsmf KO mice.
{"title":"Investigation of subfertility in the female Nsmf knockout mouse","authors":"Erica D. Louden M.D. Ph.D. , Michael P. Dougherty M.D. , Lynn P. Chorich M.S. , Ali Eroglu Ph.D., D.V.M. , Lawrence C. Layman M.D.","doi":"10.1016/j.xfss.2023.07.003","DOIUrl":"10.1016/j.xfss.2023.07.003","url":null,"abstract":"<div><h3>Objective</h3><p><span>To study if a pituitary or ovarian defect contributes to subfertility of the female </span><em>Nsmf</em><span> knockout (KO) mouse, an animal model of the hypogonadotropic hypogonadism gene </span><em>NSMF.</em></p></div><div><h3>Design</h3><p><span>Analysis of hypothalamic, pituitary and ovarian gene expression at baseline, serum gonadotropin levels before and after gonadotropin-releasing hormone (GnRH) stimulation, ovarian response and implantation after </span>superovulation<span><span>, gonadotropin effects after ovariectomy, and ovarian NSMF </span>protein expression.</span></p></div><div><h3>Setting</h3><p>University research laboratory.</p></div><div><h3>Patients</h3><p>None; mice were used.</p></div><div><h3>Interventions</h3><p>Gonadotropin-releasing hormone stimulation, superovulation, and ovariectomy in separate experiments.</p></div><div><h3>Main Outcome Measures</h3><p>Gene expression in the hypothalamus<span>, pituitary, and ovary; ovarian response and implantation after superovulation; serum gonadotropins after GnRH stimulation and ovariectomy; Western blot to measure ovarian NSMF expression.</span></p></div><div><h3>Results</h3><p>We found increased hypothalamic <em>Kiss1, Gnrh1</em>, and <em>Jak2</em> mRNA expression in female <em>Nsmf</em><span> KO vs. wild type (WT) mice. However, pituitary gonadotropin, and GnRH receptor gene expression was not affected, and serum gonadotropin levels were normal. Gonadotropins increased after ovariectomy for both groups. Baseline </span><em>Kiss1, Fshr, Prkaca, Prkar1a</em>, and <em>Gdf9</em> ovarian mRNA expression was increased and <em>Cyp19a1</em> expression was decreased in <em>Nsmf</em> KO mice, while superovulated <em>Nsmf</em> KO mice had reduced ovarian <em>Kiss1r, Prkar1a</em>, and <em>Fshr</em> mRNA expression, 50% less oocytes, and normal implantation. Western blot demonstrated NSMF protein expression in the ovary of WT mice.</p></div><div><h3>Conclusions</h3><p>Altered hypothalamic and ovarian gene expression was demonstrated in female <em>Nsmf</em> KO mice. It is possible that increased hypothalamic <em>Gnrh1</em> and <em>Kiss1</em><span> mRNA expression could compensate for reduced NSMF enabling a normal pituitary gonadotropin response. Impaired superovulation response, altered ovarian gene expression, and decreased number of oocytes indicate ovarian dysfunction, but a uterine factor cannot be excluded. These findings provide an anatomic basis for future mechanistic studies of subfertility in female </span><em>Nsmf</em> KO mice.</p></div>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9943632","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号