Reproductive biology最新文献

Duration of gonadotropin support influences follicle growth and oocyte developmental competence in prepubertal calves

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-02-21 DOI: 10.1016/j.repbio.2025.100996

Ana Rita Tavares Krause , Fernanda Caminha Faustino Dias , Gregg Patrick Adams , Reuben John Mapletoft , Jaswant Singh

The effect of duration of FSH support on follicle growth and oocyte developmental competence in prepubertal calves was investigated. Experiment 1 tested the effects of duration of FSH support (4 vs 7 days) and method of oocyte maturation (in vitro vs. in vivo) and provided a comparison with sexually mature heifers. Despite the compromising effect of unexpected ovulations in some prepubertal calves, embryo development from oocytes collected following 4 days of FSH support and in vitro maturation was similar to that from sexually mature heifers after 7 days of FSH support and in vivo maturation. In Experiment 2, prepubertal calves were given 4, 6 or 7 days of FSH support and oocytes were matured in vitro. At the time of oocyte collection, the number of follicles ≥ 6 mm was greater (P = 0.03) in calves given 7 days of FSH treatment than 4 days (37.3 ± 5.5 vs. 14.7 ± 2.5), but the number of cumulus-oocyte complexes collected did not differ among groups (P = 0.1). Oocytes from prepubertal calves given 6 days of FSH treatment had higher rates of cleavage and blastocyst formation than 4 or 7 days of treatment (cleavage = 73.2 vs. 51.3 vs. 47.2 % respectively, P = 0.01; blastocyst = 40.9 vs. 20.5 vs. 20.2 % respectively, P = 0.02). In conclusion, six days of FSH support under controlled endogenous LH release by exogenous progesterone in 5-month-old prepubertal calves was associated with greater developmental competence of oocytes than 4 or 7 days.

{"title":"Duration of gonadotropin support influences follicle growth and oocyte developmental competence in prepubertal calves","authors":"Ana Rita Tavares Krause , Fernanda Caminha Faustino Dias , Gregg Patrick Adams , Reuben John Mapletoft , Jaswant Singh","doi":"10.1016/j.repbio.2025.100996","DOIUrl":"10.1016/j.repbio.2025.100996","url":null,"abstract":"<div><div>The effect of duration of FSH support on follicle growth and oocyte developmental competence in prepubertal calves was investigated. Experiment 1 tested the effects of duration of FSH support (4 vs 7 days) and method of oocyte maturation (in vitro vs. in vivo) and provided a comparison with sexually mature heifers. Despite the compromising effect of unexpected ovulations in some prepubertal calves, embryo development from oocytes collected following 4 days of FSH support and in vitro maturation was similar to that from sexually mature heifers after 7 days of FSH support and in vivo maturation. In Experiment 2, prepubertal calves were given 4, 6 or 7 days of FSH support and oocytes were matured in vitro. At the time of oocyte collection, the number of follicles ≥ 6 mm was greater (<em>P</em> = 0.03) in calves given 7 days of FSH treatment than 4 days (37.3 ± 5.5 vs. 14.7 ± 2.5), but the number of cumulus-oocyte complexes collected did not differ among groups (<em>P</em> = 0.1). Oocytes from prepubertal calves given 6 days of FSH treatment had higher rates of cleavage and blastocyst formation than 4 or 7 days of treatment (cleavage = 73.2 vs. 51.3 vs. 47.2 % respectively, <em>P</em> = 0.01; blastocyst = 40.9 vs. 20.5 vs. 20.2 % respectively, <em>P</em> = 0.02). In conclusion, six days of FSH support under controlled endogenous LH release by exogenous progesterone in 5-month-old prepubertal calves was associated with greater developmental competence of oocytes than 4 or 7 days.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 2","pages":"Article 100996"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Post-harvest motility and morphological changes of spermatozoa following caudal epididymal recovery in farmed common eland (Tragelaphus oryx) bulls

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-02-21 DOI: 10.1016/j.repbio.2025.100997

Jerico Consolacion , Francisco Ceacero , Veit Ny , Radim Kotrba , Josef Illek , Miša Škorič , Marta Serralle , Pedro Javier Soria-Meneses , Ana Josefa Soler , Tersia Kokošková

The caudal epididymal recovery of spermatozoa has been utilised in game animal species to preserve genetically superior material after trophy hunting or slaughter, due to the difficulties of handling wild animals. Furthermore, the potential application of assisted reproductive techniques using harvested spermatozoa may contribute towards maintaining genetic diversity in isolated captive populations internationally. However, this technique requires clear and ideally simple protocols for the collection and handling of gametes after the death of the male animals, as the point of harvest is usually remote in game ranching. Therefore, this research aimed to investigate the effects of time after harvesting sperm under basic field conditions from the caudal epididymides of farmed common eland bulls in terms of their sperm motility and morphological changes. The relationship among these sperm quality parameters was also explored. Six bulls (2–2.5 years old; 203 ± 20 kg) were slaughtered, and their epididymal sperm were harvested and assessed for sperm motility and kinematics at minutes 0, 35, 70, 100, together with sperm viability, sperm head morphometry, and morphology at minutes 0, 20, 40, 60, 80 using CASA. Sperm quality sharply declined after 35 minutes of slaughter, but no effects were seen in sperm head morphometry. This study brings the first information regarding the quality of sperm retrieval from the cauda epididymides and sperm quality under physiological conditions in a uniform age group of eland. Future work should consider the effect of animal age and other individual animal traits, as well as the use of various media and extenders.

{"title":"Post-harvest motility and morphological changes of spermatozoa following caudal epididymal recovery in farmed common eland (Tragelaphus oryx) bulls","authors":"Jerico Consolacion , Francisco Ceacero , Veit Ny , Radim Kotrba , Josef Illek , Miša Škorič , Marta Serralle , Pedro Javier Soria-Meneses , Ana Josefa Soler , Tersia Kokošková","doi":"10.1016/j.repbio.2025.100997","DOIUrl":"10.1016/j.repbio.2025.100997","url":null,"abstract":"<div><div>The caudal epididymal recovery of spermatozoa has been utilised in game animal species to preserve genetically superior material after trophy hunting or slaughter, due to the difficulties of handling wild animals. Furthermore, the potential application of assisted reproductive techniques using harvested spermatozoa may contribute towards maintaining genetic diversity in isolated captive populations internationally. However, this technique requires clear and ideally simple protocols for the collection and handling of gametes after the death of the male animals, as the point of harvest is usually remote in game ranching. Therefore, this research aimed to investigate the effects of time after harvesting sperm under basic field conditions from the caudal epididymides of farmed common eland bulls in terms of their sperm motility and morphological changes. The relationship among these sperm quality parameters was also explored. Six bulls (2–2.5 years old; 203 ± 20 kg) were slaughtered, and their epididymal sperm were harvested and assessed for sperm motility and kinematics at minutes 0, 35, 70, 100, together with sperm viability, sperm head morphometry, and morphology at minutes 0, 20, 40, 60, 80 using CASA. Sperm quality sharply declined after 35 minutes of slaughter, but no effects were seen in sperm head morphometry. This study brings the first information regarding the quality of sperm retrieval from the cauda epididymides and sperm quality under physiological conditions in a uniform age group of eland. Future work should consider the effect of animal age and other individual animal traits, as well as the use of various media and extenders.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 2","pages":"Article 100997"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

E12.5 whole mouse embryo culture

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-02-03 DOI: 10.1016/j.repbio.2025.100995

Maxim A. Filatov, Leonid A. Ilchuk, Iuliia P. Baikova

Ex utero culture of postimplantation embryos remains one of the unsolved tasks in developmental biology. This technique may be required for infertility treatment, observation of embryo development and assessing the embryotoxicity of certain chemical agents. We describe novel method for E12.5 mouse embryos whole embryo culture system, which maintains embryo viability for 24 h. The culture system is based on the bubbling of pure oxygen through the culture medium. The oxygen was obtained by a chemical method. Each tube containing three embryos held 8 ml of culture medium composed of 6 ml of FBS, 2 ml of DMEM/F12, 80 μl of 40 % glucose and 30 μl of antibiotics (a mixture of penicillin 5000 UI/ml and streptomycin 5000 μg/ml). We observed initiation of auricle formation, as well as progression of eye development. Embryo viability was confirmed by the presence of heartbeat. The ratio of viable embryos after 24 h of culture was 27,78 %. However, many viable embryos exhibited massive hemorrhage attributed to oxygen insufficiency. The described culture system may be useful for the investigation of teratogenic compounds on the development of organs. Nonetheless, it is not suitable for ex utero culture of mouse embryos at more advanced stages due to the fact that embryos at such stages require more oxygen for the development than can be dissolved in the culture medium and consumed by embryos through diffusion. A potential solution to this issue is connecting the embryonic bloodstream to an oxygenator.

{"title":"E12.5 whole mouse embryo culture","authors":"Maxim A. Filatov, Leonid A. Ilchuk, Iuliia P. Baikova","doi":"10.1016/j.repbio.2025.100995","DOIUrl":"10.1016/j.repbio.2025.100995","url":null,"abstract":"<div><div><em>Ex utero</em> culture of postimplantation embryos remains one of the unsolved tasks in developmental biology. This technique may be required for infertility treatment, observation of embryo development and assessing the embryotoxicity of certain chemical agents. We describe novel method for E12.5 mouse embryos whole embryo culture system, which maintains embryo viability for 24 h. The culture system is based on the bubbling of pure oxygen through the culture medium. The oxygen was obtained by a chemical method. Each tube containing three embryos held 8 ml of culture medium composed of 6 ml of FBS, 2 ml of DMEM/F12, 80 μl of 40 % glucose and 30 μl of antibiotics (a mixture of penicillin 5000 UI/ml and streptomycin 5000 μg/ml). We observed initiation of auricle formation, as well as progression of eye development. Embryo viability was confirmed by the presence of heartbeat. The ratio of viable embryos after 24 h of culture was 27,78 %. However, many viable embryos exhibited massive hemorrhage attributed to oxygen insufficiency. The described culture system may be useful for the investigation of teratogenic compounds on the development of organs. Nonetheless, it is not suitable for <em>ex utero</em> culture of mouse embryos at more advanced stages due to the fact that embryos at such stages require more oxygen for the development than can be dissolved in the culture medium and consumed by embryos through diffusion. A potential solution to this issue is connecting the embryonic bloodstream to an oxygenator.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 2","pages":"Article 100995"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143168795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trophoblast-derived factors drive human mesenchymal stem cell differentiation along an endothelial lineage: A model of early placental vasculogenesis 滋养细胞衍生因子驱动人间充质干细胞沿内皮谱系分化：早期胎盘血管形成模型。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-01-16 DOI: 10.1016/j.repbio.2025.100994

Claire V. Harper , Leah Eccles , James Henstock , Jayne C. Charnock

Mechanisms controlling the process and patterning of blood vessel development in the placenta remain largely unknown. The close physical proximity of early blood vessels observed in the placenta and the cytotrophoblast, as well as the reported production of vasculogenic growth factors by the latter, suggests that signalling between these two niches may be important. Here, we have developed an in vitro model to address the hypothesis that the cytotrophoblast, by the secretion of soluble factors, drives differentiation of resident sub-trophoblastic mesenchymal stem cells (MSCs) along a vascular lineage, thereby establishing feto-placental circulation. BM-MSCs (a readily available model for placental stem cells) were treated with conditioned medium containing the secretome from human BeWo trophoblast cells, or endothelial growth medium (EGM2) supplemented with exogenous growth factors (VEGF, IGF1 and EGF) for 10–12 days. Trophoblast-conditioned media, found to contain detectable concentrations of cytokines including VEGF, uPAR, TIMP-1, TIMP-2, IL6 and placental growth factor, induced the expression of the endothelial genes CD31, von Willibrand factor (vWF), FLT-1, VEGFR2 and VE-Cadherin. Upregulation of vWF protein was also detected following growth in trophoblast-conditioned media, using immunocytochemistry. Wound healing (migration assay) and Matrigel-tube formation assays confirmed that the BM-MSCs cultured in trophoblast-conditioned media exhibited functional measures of endothelial cells in addition to expressing relevant markers. Identification of key trophoblast-secreted factors and their promotion of endothelial differentiation in BM-MSCs helps advance our theories regarding the close relationship of the mesenchymal stem cell-cytotrophoblast niche in coordinating the complex angiogenic events that occur in the placenta. The in vitro model presented here provides an accessible and reproducible tool for further investigations into placental development.

控制胎盘血管发育过程和模式的机制在很大程度上仍然未知。在胎盘和细胞滋养细胞中观察到的早期血管的紧密物理距离，以及后者产生血管生成生长因子的报道，表明这两个生态位之间的信号传导可能很重要。在这里，我们开发了一个体外模型来解决细胞滋养细胞，通过分泌可溶性因子，驱动居住的亚滋养层间充质干细胞（MSCs）沿着血管谱系分化的假设，从而建立胎儿-胎盘循环。BM-MSCs（一种现成的胎盘干细胞模型）用含有人BeWo滋养细胞分泌组的条件培养基或添加外源性生长因子（VEGF， IGF1和EGF）的内皮生长培养基（EGM2）处理10-12天。滋养细胞条件培养基中含有可检测浓度的细胞因子，包括VEGF、uPAR、TIMP-1、TIMP-2、IL6和胎盘生长因子，诱导内皮基因CD31、von Willibrand因子（vWF）、FLT-1、VEGFR2和VE-Cadherin的表达。免疫细胞化学方法也检测到在滋养细胞条件培养基中生长后vWF蛋白的上调。伤口愈合（迁移实验）和基质管形成实验证实，在滋养细胞条件培养基中培养的BM-MSCs除了表达相关标记物外，还表现出内皮细胞的功能指标。鉴定关键滋养细胞分泌因子及其促进BM-MSCs内皮分化的作用，有助于推进我们关于间充质干细胞-细胞滋养细胞生态位在协调胎盘中发生的复杂血管生成事件中的密切关系的理论。这里提出的体外模型为进一步研究胎盘发育提供了一个可访问和可重复的工具。

{"title":"Trophoblast-derived factors drive human mesenchymal stem cell differentiation along an endothelial lineage: A model of early placental vasculogenesis","authors":"Claire V. Harper , Leah Eccles , James Henstock , Jayne C. Charnock","doi":"10.1016/j.repbio.2025.100994","DOIUrl":"10.1016/j.repbio.2025.100994","url":null,"abstract":"<div><div>Mechanisms controlling the process and patterning of blood vessel development in the placenta remain largely unknown. The close physical proximity of early blood vessels observed in the placenta and the cytotrophoblast, as well as the reported production of vasculogenic growth factors by the latter, suggests that signalling between these two niches may be important. Here, we have developed an <em>in vitro</em> model to address the hypothesis that the cytotrophoblast, by the secretion of soluble factors, drives differentiation of resident sub-trophoblastic mesenchymal stem cells (MSCs) along a vascular lineage, thereby establishing feto-placental circulation. BM-MSCs (a readily available model for placental stem cells) were treated with conditioned medium containing the secretome from human BeWo trophoblast cells, or endothelial growth medium (EGM2) supplemented with exogenous growth factors (VEGF, IGF1 and EGF) for 10–12 days. Trophoblast-conditioned media, found to contain detectable concentrations of cytokines including VEGF, uPAR, TIMP-1, TIMP-2, IL6 and placental growth factor, induced the expression of the endothelial genes <em>CD31</em>, <em>von Willibrand factor</em> (<em>vWF</em>), <em>FLT-1</em>, <em>VEGFR2</em> and <em>VE-Cadherin</em>. Upregulation of vWF protein was also detected following growth in trophoblast-conditioned media, using immunocytochemistry. Wound healing (migration assay) and Matrigel-tube formation assays confirmed that the BM-MSCs cultured in trophoblast-conditioned media exhibited functional measures of endothelial cells in addition to expressing relevant markers. Identification of key trophoblast-secreted factors and their promotion of endothelial differentiation in BM-MSCs helps advance our theories regarding the close relationship of the mesenchymal stem cell-cytotrophoblast niche in coordinating the complex angiogenic events that occur in the placenta. The <em>in vitro</em> model presented here provides an accessible and reproducible tool for further investigations into placental development.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100994"},"PeriodicalIF":2.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early and advanced glycation end product analysis from women with PCOS on metformin 二甲双胍治疗多囊卵巢综合征妇女早期和晚期糖基化终产物分析。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-01-14 DOI: 10.1016/j.repbio.2024.100993

Aditi S. Ambekar , Nikita Naredi , Dipankar Malakar , Y. Vashum , Pratibha Misra , Mahesh Kulkarni

In this cross-sectional study, we have analyzed advanced glycation end products (AGEs) in the plasma and follicular fluid of women with polycystic ovary syndrome (PCOS) taking metformin during in vitro fertilization (IVF) and control women undergoing IVF. Glucose, fructose, fructosamine, carboxymethyl lysine/ arginine (CML/R) proteins, and pentosidine were measured in the plasma and paired follicular fluid. Glycated proteins were characterized by mass spectrometry. Fasting serum glucose and fructosamine were comparable; however, follicular fluid glucose and fructosamine were higher in the PCOS group, and other AGEs remained unaltered. Fructose was lower in both serum and follicular fluid from the PCOS group. A positive correlation between some of these AGEs and sugars estimated was observed. Glucose and fructosamine in the follicular fluid correlated with the antral follicle count. The number of glycated peptides identified in the PCOS group by mass spectrometry was more. Glycated K75, K402 amino acid residues of albumin were detected in the PCOS group only. Additionally, some proteins involved in steroidogenesis and oocyte maturation as well as transporters, and extracellular matrix proteins, were found to be glycated in the PCOS group, which may affect their function. Elevated glucose and fructosamine in the follicular fluid of the PCOS group may contribute to abnormal folliculogenesis. The glycation of albumin should be validated in more samples to be considered as a marker for PCOS diagnosis.

在这项横断面研究中，我们分析了在体外受精（IVF）期间服用二甲双胍的多囊卵巢综合征（PCOS）妇女和接受体外受精（IVF）的对照组妇女血浆和卵泡液中的晚期糖基化终产物（AGEs）。测定血浆和配对卵泡液中的葡萄糖、果糖、果糖胺、羧甲基赖氨酸/精氨酸（CML/R）蛋白和戊苷。糖化蛋白用质谱法进行表征。空腹血糖和果糖胺比较；然而，卵泡液葡萄糖和果糖胺在多囊卵巢综合征组较高，其他AGEs保持不变。多囊卵巢综合征组血清和卵泡液中果糖含量均较低。观察到一些AGEs与糖估计值之间存在正相关。卵泡液中的葡萄糖和果糖胺与窦卵泡计数相关。质谱法鉴定PCOS组糖基化肽的数量更多。仅PCOS组检测到白蛋白糖化K75、K402氨基酸残基。此外，一些参与甾体生成和卵母细胞成熟的蛋白质以及转运蛋白和细胞外基质蛋白在PCOS组中被发现糖化，这可能会影响它们的功能。多囊卵巢综合征患者卵泡液中葡萄糖和果糖胺升高可能导致卵泡发生异常。白蛋白糖基化应在更多的样本中进行验证，以作为多囊卵巢综合征诊断的标志。

{"title":"Early and advanced glycation end product analysis from women with PCOS on metformin","authors":"Aditi S. Ambekar , Nikita Naredi , Dipankar Malakar , Y. Vashum , Pratibha Misra , Mahesh Kulkarni","doi":"10.1016/j.repbio.2024.100993","DOIUrl":"10.1016/j.repbio.2024.100993","url":null,"abstract":"<div><div>In this cross-sectional study, we have analyzed advanced glycation end products (AGEs) in the plasma and follicular fluid of women with polycystic ovary syndrome (PCOS) taking metformin during <em>in vitro</em> fertilization (IVF) and control women undergoing IVF. Glucose, fructose, fructosamine, carboxymethyl lysine/ arginine (CML/R) proteins, and pentosidine were measured in the plasma and paired follicular fluid. Glycated proteins were characterized by mass spectrometry. Fasting serum glucose and fructosamine were comparable; however, follicular fluid glucose and fructosamine were higher in the PCOS group, and other AGEs remained unaltered. Fructose was lower in both serum and follicular fluid from the PCOS group. A positive correlation between some of these AGEs and sugars estimated was observed. Glucose and fructosamine in the follicular fluid correlated with the antral follicle count. The number of glycated peptides identified in the PCOS group by mass spectrometry was more. Glycated K75, K402 amino acid residues of albumin were detected in the PCOS group only. Additionally, some proteins involved in steroidogenesis and oocyte maturation as well as transporters, and extracellular matrix proteins, were found to be glycated in the PCOS group, which may affect their function. Elevated glucose and fructosamine in the follicular fluid of the PCOS group may contribute to abnormal folliculogenesis. The glycation of albumin should be validated in more samples to be considered as a marker for PCOS diagnosis.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100993"},"PeriodicalIF":2.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel screening approach for stem cell selective inhibitors and their possible translational therapeutic potential for endometriosis 干细胞选择性抑制剂的新型筛选方法及其对子宫内膜异位症可能的转化治疗潜力。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-01-11 DOI: 10.1016/j.repbio.2024.100992

Naoki Kimura , Tomoka Takao , Kazunori Imada , Masanori Nakakuki , Satoshi Kajikawa , Tetsuo Maruyama

Endometriosis is an estrogen-dependent benign disease characterized by growth of the endometrial tissue outside the uterine wall. Several reports suggest the possibility of the pathogenesis and recurrence of endometriosis being related to functions of stem/progenitor cells of the endometrium. The drawback of the widely used method of using Hoechst 33342, a fluorescent dye, to collect stem cell-like populations, is the requirement of an ultraviolet (UV) excitation source not commonly provided on standard flow cytometers. Here, we aimed to overcome this hurdle by establishing a novel method that uses DyeCycle Green (DCG), a cell-permeable DNA dye, for collecting a significantly higher fraction of stem cell-like side population (SP) from HHUA cells (human endometrial cancer cell line) with standard equipment without a UV laser. Furthermore, subculturing the DCG-SP cells expanded their population remarkably. The DCG-SP cells possessed stem cell-like characteristics with high expression of stem cell markers such as aldehyde dehydrogenase 1 A (ALDH1A), sushi domain containing 2 (SUSD2), increased colony formation ability, and high tumorigenicity in vivo, although the expression of some stem cell markers varied during expansion. We screened inhibitors for selective proliferation of the DCG-SP cells over immortalized endometrial cells (EM-E6/E7/hTERT-2 cells) and identified two effective compounds disulfiram and NSC319726. In addition, these compounds inhibited the colony formation and invasiveness of the DCG-SP cells. Our DCG-mediated screening of SP cells would possibly be translational to identify compounds that selectively target stem cells for the treatment and inhibition of recurrence of endometriosis.

子宫内膜异位症是一种雌激素依赖的良性疾病，其特征是子宫壁外子宫内膜组织的生长。一些报道认为子宫内膜异位症的发病和复发可能与子宫内膜干细胞/祖细胞的功能有关。广泛使用的使用Hoechst 33342（一种荧光染料）收集干细胞样群体的方法的缺点是需要紫外线（UV）激发源，而标准流式细胞仪通常不提供这种激发源。在这里，我们的目标是克服这一障碍，通过建立一种新方法，使用DyeCycle Green (DCG)，一种细胞渗透性DNA染料，从HHUA细胞（人类子宫内膜癌细胞系）中收集更高比例的干细胞样侧群（SP），使用标准设备，无需紫外线激光。此外，传代培养的DCG-SP细胞数量显著增加。DCG-SP细胞具有干细胞样特征，在体内高表达醛脱氢酶1 A （ALDH1A）、含sushi结构域2 （SUSD2）等干细胞标记物，集落形成能力增强，具有较高的致瘤性，尽管一些干细胞标记物的表达在扩增过程中发生变化。我们筛选了DCG-SP细胞对永生化子宫内膜细胞（EM-E6/E7/hTERT-2细胞）选择性增殖的抑制剂，并鉴定了两种有效化合物双硫仑和NSC319726。此外，这些化合物抑制DCG-SP细胞的集落形成和侵袭性。我们的dcg介导的SP细胞筛选可能具有翻译意义，可以识别选择性靶向干细胞治疗和抑制子宫内膜异位症复发的化合物。

{"title":"Novel screening approach for stem cell selective inhibitors and their possible translational therapeutic potential for endometriosis","authors":"Naoki Kimura , Tomoka Takao , Kazunori Imada , Masanori Nakakuki , Satoshi Kajikawa , Tetsuo Maruyama","doi":"10.1016/j.repbio.2024.100992","DOIUrl":"10.1016/j.repbio.2024.100992","url":null,"abstract":"<div><div>Endometriosis is an estrogen-dependent benign disease characterized by growth of the endometrial tissue outside the uterine wall. Several reports suggest the possibility of the pathogenesis and recurrence of endometriosis being related to functions of stem/progenitor cells of the endometrium. The drawback of the widely used method of using Hoechst 33342, a fluorescent dye, to collect stem cell-like populations, is the requirement of an ultraviolet (UV) excitation source not commonly provided on standard flow cytometers. Here, we aimed to overcome this hurdle by establishing a novel method that uses DyeCycle Green (DCG), a cell-permeable DNA dye, for collecting a significantly higher fraction of stem cell-like side population (SP) from HHUA cells (human endometrial cancer cell line) with standard equipment without a UV laser. Furthermore, subculturing the DCG-SP cells expanded their population remarkably. The DCG-SP cells possessed stem cell-like characteristics with high expression of stem cell markers such as aldehyde dehydrogenase 1 A (ALDH1A), sushi domain containing 2 (SUSD2), increased colony formation ability, and high tumorigenicity in vivo, although the expression of some stem cell markers varied during expansion. We screened inhibitors for selective proliferation of the DCG-SP cells over immortalized endometrial cells (EM-E6/E7/hTERT-2 cells) and identified two effective compounds disulfiram and NSC319726. In addition, these compounds inhibited the colony formation and invasiveness of the DCG-SP cells. Our DCG-mediated screening of SP cells would possibly be translational to identify compounds that selectively target stem cells for the treatment and inhibition of recurrence of endometriosis.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100992"},"PeriodicalIF":2.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insulin and myometrial contractility; Are there any links? A narrative review 胰岛素与子宫肌收缩力之间是否存在联系？叙述性综述。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-01-10 DOI: 10.1016/j.repbio.2024.100991

Pedram Ghafourifar , Zahra Farahani , Amir Hossein Norooznezhad , Sedigheh Hantoushzadeh , Mansour Azimzadeh , Seyedeh Maedeh Nabavian , Arezo Behzadian , Quinn Kern Allely

Contrary to the evidence supporting the role for insulin in stimulating uterine contraction, only a limited number of studies have highlighted the inhibitory effect of insulin on myometrial contractions in human and rodent. A hypothetical narrative review of the current literature was conducted, revealing the current literature and shows the potential inhibitory effects of insulin on myometrial contractility. These inhibitory mechanisms include activation of adenylyl cyclase signaling pathways, an increase in cAMP production, a decrease in Ca^2 + influx and cytosolic Ca²⁺, hyperpolarization of the cell membrane, and stimulation of NO synthesis. Altered oxytocin sensitivity, structural similarity to relaxin, modulating abscisic acid (ABA) effect, and synergistic interaction with progesterone, adiponectin, and leptin may also represent additional mechanisms for the inhibitory effects of insulin on myometrial contractions. The literature indicates that insulin exhibits inhibitory effects on myometrial contractility. Confirming such a conclusion through future studies may propose insulin as a possible uterine quiescent.

与支持胰岛素刺激子宫收缩作用的证据相反，只有少数研究强调了胰岛素对人类和啮齿动物子宫肌收缩的抑制作用。我们对现有文献进行了假设性叙述回顾，揭示了现有文献并显示了胰岛素对子宫肌收缩的潜在抑制作用。这些抑制机制包括激活腺苷酸环化酶信号通路、增加 cAMP 生成、减少 Ca2 + 流入和细胞膜 Ca2+、细胞膜超极化以及刺激 NO 合成。催产素敏感性的改变、与松弛素结构的相似性、脱落酸（ABA）的调节作用以及与孕酮、脂肪连接素和瘦素的协同作用也可能是胰岛素对子宫肌收缩产生抑制作用的其他机制。文献表明，胰岛素对子宫肌收缩有抑制作用。通过未来的研究证实这一结论，可能会提出胰岛素是一种可能的子宫收缩剂。

{"title":"Insulin and myometrial contractility; Are there any links? A narrative review","authors":"Pedram Ghafourifar , Zahra Farahani , Amir Hossein Norooznezhad , Sedigheh Hantoushzadeh , Mansour Azimzadeh , Seyedeh Maedeh Nabavian , Arezo Behzadian , Quinn Kern Allely","doi":"10.1016/j.repbio.2024.100991","DOIUrl":"10.1016/j.repbio.2024.100991","url":null,"abstract":"<div><div>Contrary to the evidence supporting the role for insulin in stimulating uterine contraction, only a limited number of studies have highlighted the inhibitory effect of insulin on myometrial contractions in human and rodent. A hypothetical narrative review of the current literature was conducted, revealing the current literature and shows the potential inhibitory effects of insulin on myometrial contractility. These inhibitory mechanisms include activation of adenylyl cyclase signaling pathways, an increase in cAMP production, a decrease in Ca<sup>2 +</sup> influx and cytosolic Ca<sup>2+</sup>, hyperpolarization of the cell membrane, and stimulation of NO synthesis. Altered oxytocin sensitivity, structural similarity to relaxin, modulating abscisic acid (ABA) effect, and synergistic interaction with progesterone, adiponectin, and leptin may also represent additional mechanisms for the inhibitory effects of insulin on myometrial contractions. The literature indicates that insulin exhibits inhibitory effects on myometrial contractility. Confirming such a conclusion through future studies may propose insulin as a possible uterine quiescent.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100991"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclophosphamide-induced testicular injury is associated with inflammation, oxidative stress, and apoptosis in mice: Protective role of taxifolin

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2025-01-06 DOI: 10.1016/j.repbio.2024.100990

Afaf F. Almuqati

Testicular damage is a major complication of chemotherapeutic cyclophosphamide (CP) compound. Taxifolin (TX), a natural flavonoid with well-established anti-inflammatory and antioxidant properties, is commonly found in various medicinal plants and foods. This study investigated the protective effect of TX against testicular damage in CP-administered mice. Mice were administered with TX at the doses of 10, 25, and 50 mg/kg for 15 days followed by a single CP injection on the 16th day. CP-administered mice demonstrated significantly decreased testosterone levels and low sperm parameters (count, viability, motility). TX administration significantly improved sperm parameters and testosterone levels and effectively mitigated histopathological testicular changes in CP-administered animals. Moreover, TX administration decreased oxidative stress markers and boosted antioxidants (superoxide dismutase, catalase, and reduced glutathione), suppressed and NF-κB p65 and pro-inflammatory cytokines [TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6)], and reduced apoptosis as depicted by testicular levels of caspase-3, Bcl-2, and Bax. Thus, TX could be a highly potent compound to counter CP-linked testicular damage through modulation of oxidative stress, inflammation, and apoptosis, warranting further studies to evaluate the role of TX in human CP-induced testicular injury.

{"title":"Cyclophosphamide-induced testicular injury is associated with inflammation, oxidative stress, and apoptosis in mice: Protective role of taxifolin","authors":"Afaf F. Almuqati","doi":"10.1016/j.repbio.2024.100990","DOIUrl":"10.1016/j.repbio.2024.100990","url":null,"abstract":"<div><div>Testicular damage is a major complication of chemotherapeutic cyclophosphamide (CP) compound. Taxifolin (TX), a natural flavonoid with well-established anti-inflammatory and antioxidant properties, is commonly found in various medicinal plants and foods. This study investigated the protective effect of TX against testicular damage in CP-administered mice. Mice were administered with TX at the doses of 10, 25, and 50 mg/kg for 15 days followed by a single CP injection on the 16th day. CP-administered mice demonstrated significantly decreased testosterone levels and low sperm parameters (count, viability, motility). TX administration significantly improved sperm parameters and testosterone levels and effectively mitigated histopathological testicular changes in CP-administered animals. Moreover, TX administration decreased oxidative stress markers and boosted antioxidants (superoxide dismutase, catalase, and reduced glutathione), suppressed and NF-κB p65 and pro-inflammatory cytokines [TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6)], and reduced apoptosis as depicted by testicular levels of caspase-3, Bcl-2, and Bax. Thus, TX could be a highly potent compound to counter CP-linked testicular damage through modulation of oxidative stress, inflammation, and apoptosis, warranting further studies to evaluate the role of TX in human CP-induced testicular injury.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100990"},"PeriodicalIF":2.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143098962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the endocrine-disrupting potential of atrazine for male reproduction: A systematic review and meta-analysis 探索阿特拉津对男性生殖的内分泌干扰潜力：一项系统综述和荟萃分析。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2024-12-20 DOI: 10.1016/j.repbio.2024.100989

Luiz Otávio Guimarães-Ervilha, Mírian Quintão Assis, Isabela Pereira da Silva Bento, Izabela da Silva Lopes, Thainá Iasbik-Lima, Renner Philipe Rodrigues Carvalho, Mariana Machado-Neves

Atrazine is an herbicide widely used on plantations worldwide. Experimental studies suggest that the herbicide impairs male reproductive function in mammals. This systematic review and meta-analysis aimed to evaluate the impact of atrazine exposure on the levels of hormones from the hypothalamic-pituitary-testicular axis using murine as the animal model. After an extensive literature search, we selected 25 articles for the systematic review. Bias analysis and methodological quality assessments were examined using the SYRCLE Risk of Bias tool. Moreover, 20 out of the 25 studies were eligible for performing a meta-analysis to evaluate the intensity of atrazine damage on the levels of intratesticular testosterone and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and progesterone. The meta-analysis revealed that atrazine exposure decreased serum FSH, LH, and testosterone levels, besides increased serum estradiol and progesterone levels. Atrazine also caused a reduction in intratesticular testosterone levels. Exposure to atrazine in high concentrations (≥ 100 mg Kg⁻¹) was the main cause of endocrine disruption, regardless of the exposure time. None of the studies have tested doses relevant to human health risk. Oxidative stress and inflammation are involved in atrazine toxicity, impairing the gonadotropin release by the pituitary, disturbing steroidogenesis, and affecting the male hormone regulatory system. We may conclude that hormone disturbances lead to a failure in testicular steroidogenesis, with possible implications for male reproductive function. The registration number on the Prospero platform is CRD42024495626.

阿特拉津是一种广泛用于世界各地种植园的除草剂。实验研究表明，除草剂会损害哺乳动物的雄性生殖功能。本系统综述和荟萃分析旨在以小鼠为动物模型，评估阿特拉津暴露对下丘脑-垂体-睾丸轴激素水平的影响。经过广泛的文献检索，我们选择了25篇文章进行系统评价。使用cycle偏倚风险工具检查偏倚分析和方法学质量评估。此外，25项研究中有20项有资格进行荟萃分析，以评估阿特拉津对睾丸内睾酮和血清促卵泡激素（FSH）、黄体生成素（LH）、睾酮、雌二醇和黄体酮水平的损害程度。荟萃分析显示，阿特拉津暴露降低了血清FSH、LH和睾酮水平，同时增加了血清雌二醇和黄体酮水平。阿特拉津还会导致睾丸内睾丸激素水平降低。高浓度暴露于阿特拉津（≥100 mg Kg-1）是导致内分泌紊乱的主要原因，与暴露时间无关。没有一项研究测试了与人类健康风险相关的剂量。氧化应激和炎症参与阿特拉津毒性，损害垂体释放促性腺激素，扰乱类固醇生成，影响男性激素调节系统。我们可以得出这样的结论：激素紊乱导致睾丸类固醇生成失败，可能影响男性生殖功能。普洛斯彼罗平台的注册号为CRD42024495626。

{"title":"Exploring the endocrine-disrupting potential of atrazine for male reproduction: A systematic review and meta-analysis","authors":"Luiz Otávio Guimarães-Ervilha, Mírian Quintão Assis, Isabela Pereira da Silva Bento, Izabela da Silva Lopes, Thainá Iasbik-Lima, Renner Philipe Rodrigues Carvalho, Mariana Machado-Neves","doi":"10.1016/j.repbio.2024.100989","DOIUrl":"10.1016/j.repbio.2024.100989","url":null,"abstract":"<div><div>Atrazine is an herbicide widely used on plantations worldwide. Experimental studies suggest that the herbicide impairs male reproductive function in mammals. This systematic review and meta-analysis aimed to evaluate the impact of atrazine exposure on the levels of hormones from the hypothalamic-pituitary-testicular axis using murine as the animal model. After an extensive literature search, we selected 25 articles for the systematic review. Bias analysis and methodological quality assessments were examined using the SYRCLE Risk of Bias tool. Moreover, 20 out of the 25 studies were eligible for performing a meta-analysis to evaluate the intensity of atrazine damage on the levels of intratesticular testosterone and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and progesterone. The meta-analysis revealed that atrazine exposure decreased serum FSH, LH, and testosterone levels, besides increased serum estradiol and progesterone levels. Atrazine also caused a reduction in intratesticular testosterone levels. Exposure to atrazine in high concentrations (≥ 100 mg Kg<sup>−1</sup>) was the main cause of endocrine disruption, regardless of the exposure time. None of the studies have tested doses relevant to human health risk. Oxidative stress and inflammation are involved in atrazine toxicity, impairing the gonadotropin release by the pituitary, disturbing steroidogenesis, and affecting the male hormone regulatory system. We may conclude that hormone disturbances lead to a failure in testicular steroidogenesis, with possible implications for male reproductive function. The registration number on the Prospero platform is CRD42024495626.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100989"},"PeriodicalIF":2.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metformin-induced RBMS3 expression enhances ferroptosis and suppresses ovarian cancer progression 二甲双胍诱导的RBMS3表达增强铁下垂并抑制卵巢癌进展。

IF 2.5 3区生物学 Q3 REPRODUCTIVE BIOLOGY

Reproductive biology

Pub Date : 2024-12-16 DOI: 10.1016/j.repbio.2024.100968

Yue Zhao , Yixiao Wang , Xinyi Zhang, Shuqi Han, Bo Yang

Metformin (Met), a widely used type II diabetes medication, has shown anti-cancer properties in various cancers. RBMS3 is a tumor suppressor implicated in several cancers, including ovarian cancer. Ferroptosis, a novel form of programmed cell death, is gaining attention in cancer research. This study explores whether metformin induces ferroptosis and inhibits ovarian cancer progression through the RBMS3 pathway. We used a CCK-8 assay to determine the optimal metformin concentration for ovarian cancer cells. Metformin’s effects were further evaluated using EdU assay and flow cytometry. To clarify its mechanism, we employed programmed cell death inhibitors and measured levels of MDA (Malondialdehyde), GSH (Glutathione), and Fe²⁺. Ferroptosis-related proteins and RBMS3 expression in ovarian cancer tissues and cells were assessed via RT-qPCR and Western blotting. A xenograft mouse model was used to observe metformin’s effects on tumor growth. Metformin inhibited the viability of ovarian cancer A2780 cells, promoted ferroptosis, increased MDA and Fe²⁺ levels, and reduced GSH. It upregulated ferroptosis-related genes while downregulating GPX4 and SLC7A11. Although RBMS3 was reduced in cancer cells, metformin increased its expression, and silencing RBMS3 reversed metformin’s effects. In vivo, metformin inhibited tumor growth, which was negated by RBMS3 silencing. Our findings suggest that metformin promotes ferroptosis and inhibits ovarian cancer progression by upregulating RBMS3, offering a promising direction for clinical application in ovarian cancer treatment.

二甲双胍（Metformin, Met）是一种广泛应用于II型糖尿病的药物，在多种癌症中显示出抗癌特性。RBMS3是一种肿瘤抑制因子，与包括卵巢癌在内的几种癌症有关。铁下垂是一种新的程序性细胞死亡形式，在癌症研究中越来越受到关注。本研究探讨二甲双胍是否通过RBMS3途径诱导铁下垂并抑制卵巢癌进展。我们使用CCK-8测定法来确定卵巢癌细胞的最佳二甲双胍浓度。用EdU法和流式细胞术进一步评价二甲双胍的作用。为了阐明其机制，我们使用了程序性细胞死亡抑制剂，并测量了MDA（丙二醛）、GSH（谷胱甘肽）和Fe 2⁺的水平。通过RT-qPCR和Western blotting检测卵巢癌组织和细胞中凋亡相关蛋白和RBMS3的表达。采用异种移植小鼠模型观察二甲双胍对肿瘤生长的影响。二甲双胍抑制卵巢癌A2780细胞活力，促进铁凋亡，增加MDA和Fe 2 +水平，降低GSH。上调铁凋亡相关基因，下调GPX4和SLC7A11。虽然RBMS3在癌细胞中减少，但二甲双胍增加了其表达，沉默RBMS3逆转了二甲双胍的作用。在体内，二甲双胍抑制肿瘤生长，而RBMS3沉默则对肿瘤生长无抑制作用。我们的研究结果表明，二甲双胍通过上调RBMS3促进铁下垂，抑制卵巢癌进展，为卵巢癌临床应用提供了一个有希望的方向。

{"title":"Metformin-induced RBMS3 expression enhances ferroptosis and suppresses ovarian cancer progression","authors":"Yue Zhao , Yixiao Wang , Xinyi Zhang, Shuqi Han, Bo Yang","doi":"10.1016/j.repbio.2024.100968","DOIUrl":"10.1016/j.repbio.2024.100968","url":null,"abstract":"<div><div>Metformin (Met), a widely used type II diabetes medication, has shown anti-cancer properties in various cancers. RBMS3 is a tumor suppressor implicated in several cancers, including ovarian cancer. Ferroptosis, a novel form of programmed cell death, is gaining attention in cancer research. This study explores whether metformin induces ferroptosis and inhibits ovarian cancer progression through the RBMS3 pathway. We used a CCK-8 assay to determine the optimal metformin concentration for ovarian cancer cells. Metformin’s effects were further evaluated using EdU assay and flow cytometry. To clarify its mechanism, we employed programmed cell death inhibitors and measured levels of MDA (Malondialdehyde), GSH (Glutathione), and Fe²⁺. Ferroptosis-related proteins and RBMS3 expression in ovarian cancer tissues and cells were assessed via RT-qPCR and Western blotting. A xenograft mouse model was used to observe metformin’s effects on tumor growth. Metformin inhibited the viability of ovarian cancer A2780 cells, promoted ferroptosis, increased MDA and Fe²⁺ levels, and reduced GSH. It upregulated ferroptosis-related genes while downregulating GPX4 and SLC7A11. Although RBMS3 was reduced in cancer cells, metformin increased its expression, and silencing RBMS3 reversed metformin’s effects. In vivo, metformin inhibited tumor growth, which was negated by RBMS3 silencing. Our findings suggest that metformin promotes ferroptosis and inhibits ovarian cancer progression by upregulating RBMS3, offering a promising direction for clinical application in ovarian cancer treatment.</div></div>","PeriodicalId":21018,"journal":{"name":"Reproductive biology","volume":"25 1","pages":"Article 100968"},"PeriodicalIF":2.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0