Linkai Zhu, Hao Ming, Giovanna N Scatolin, Andrew Xiao, Zongliang Jiang
{"title":"METTL7A improves bovine IVF embryo competence by attenuating oxidative stress†.","authors":"Linkai Zhu, Hao Ming, Giovanna N Scatolin, Andrew Xiao, Zongliang Jiang","doi":"10.1093/biolre/ioaf018","DOIUrl":"10.1093/biolre/ioaf018","url":null,"abstract":"<p><p>In vitro fertilization is a widely used assisted reproductive technology to achieve a successful pregnancy. However, the acquisition of oxidative stress in embryo in vitro culture impairs its competence. Here, we demonstrated that a nuclear coding gene, methyltransferase-like protein 7A, improves the developmental potential of bovine embryos. We found that exogenous methyltransferase-like protein 7A modulates expression of genes involved in embryonic cell mitochondrial pathways and promotes trophectoderm development. Surprisingly, we discovered that methyltransferase-like protein 7A alleviates mitochondrial stress and DNA damage and promotes cell cycle progression during embryo cleavage. In summary, we have identified a novel mitochondria stress eliminating mechanism regulated by methyltransferase-like protein 7A that occurs during the acquisition of oxidative stress in embryo in vitro culture. This discovery lays the groundwork for the development of methyltransferase-like protein 7A as a promising therapeutic target for in vitro fertilization embryo competence.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"628-639"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jia He, Zican Wang, Lici Yang, Yongjian Jiang, Ge Yan, Yongwei Pan, Fei Gao, Jinxiang Yuan, Yang Gao
{"title":"Unveiling the role of FOXL2 in female differentiation and disease: a comprehensive review†.","authors":"Jia He, Zican Wang, Lici Yang, Yongjian Jiang, Ge Yan, Yongwei Pan, Fei Gao, Jinxiang Yuan, Yang Gao","doi":"10.1093/biolre/ioaf013","DOIUrl":"10.1093/biolre/ioaf013","url":null,"abstract":"<p><p>Ovarian differentiation relies on the accurate and orderly expression of numerous related genes. Forkhead box protein L2 (FOXL2) is one of the earliest ovarian differentiation markers and transcription factors. In sex determination, FOXL2 maintains the differentiation of the female pathway by inhibiting male differentiation genes, including SOX9 and SF1. In addition, FOXL2 promotes the synthesis of follicle-stimulating hormone and anti-Müllerian hormone to support follicle development. Mutations in FOXL2 are associated with numerous female reproductive diseases. A comprehensive and in-depth study of FOXL2 provides novel strategies for the diagnosis and treatment of such diseases. This review discusses the mechanism of FOXL2 in female sex differentiation and maintenance, hormone synthesis, and disease occurrence and reveals the role of FOXL2 as a central factor in female sex development and fertility maintenance. This review will serve as a reference for identifying novel targets of other regulatory factors interacting with FOXL2 in female sex determination and follicle development and for the diagnosis and treatment of female reproductive diseases.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"600-613"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: The pathogenesis of endometriosis and adenomyosis: insights from single-cell RNA sequencing.","authors":"","doi":"10.1093/biolre/ioae184","DOIUrl":"10.1093/biolre/ioae184","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"780"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Roles of histone post-translational modifications in meiosis.","authors":"","doi":"10.1093/biolre/ioaf024","DOIUrl":"10.1093/biolre/ioaf024","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"781"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liqun Ouyang, Xia Gao, Rongyu Yang, Peiyi Zhou, Han Cai, Yingpu Tian, Haibin Wang, Shuangbo Kong, Zhongxian Lu
{"title":"SHP2 regulates the HIF-1 signaling pathway in the decidual human endometrial stromal cells†.","authors":"Liqun Ouyang, Xia Gao, Rongyu Yang, Peiyi Zhou, Han Cai, Yingpu Tian, Haibin Wang, Shuangbo Kong, Zhongxian Lu","doi":"10.1093/biolre/ioaf019","DOIUrl":"10.1093/biolre/ioaf019","url":null,"abstract":"<p><p>The decidual endometrial stromal cells play a critical role in the establishment of uterine receptivity and pregnancy in human. Our previous studies demonstrate that protein tyrosine phosphatase 2 SHP2 is highly expressed in decidualized cells and governs the decidualization progress. However, the role and mechanism of SHP2 in the function of decidual cells remain unclear. Here, we screened proteins interacting with SHP2 in decidual hTERT-immortalized human endometrial stromal cells (T-HESCs) and identified Hypoxia-inducible factor-1 (HIF-1) signaling pathway as a potential SHP2-mediated signaling pathway through proximity-dependent biotinylation (BioID) analysis. Immunoprecipitation (Co-IP) revealed an interaction between SHP2 and HIF-1α, which colocalized to the nucleus in decidual cells. Furthermore, the SHP2 expression correlated with the transcriptional activation of HIF-1α and its downstream genes Beta-enolase (Eno3), Pyruvate kinase 2 (Pkm2), Aldolase C (Aldoc), and Facilitative glucose transporter 1 (Glut1). Knockdown or inhibition of SHP2 significantly reduced the mRNA and protein levels of HIF-1α and its downstream genes, as well as lactate production in decidual cells. We also established a hypoxia model of T-HESCs and 293 T cells and found that hypoxic treatment induced the expression of SHP2 and HIF-1α, which colocalized in the nucleus. SHP2 forced-expression rescued the inhibitory effects of SHP2 deficiency on HIF-1α expression and lactate production. Finally, SHP2 binds to the promoter regions of HIF-1α and its target genes (Eno3, Pkm2, Aldoc, and Glut1). Collectively, our results suggest that SHP2 influences the function of decidual cells by HIF-1α signaling and provide a novel function mechanism of decidual stromal cells.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"743-753"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phosphatase and tensin homolog deficiency induces M2 macrophage polarization by promoting glycolytic activity in endometrial stromal cells.","authors":"Fengqin Dai, Jinjin Li, Yingwei Liu","doi":"10.1093/biolre/ioaf016","DOIUrl":"10.1093/biolre/ioaf016","url":null,"abstract":"<p><p>Endometriosis is a common gynecological disorder, whose pathogenesis remains incompletely understood. Macrophages, a key type of immune cell, are pivotal in the context of endometriosis. This study seeks to explore the interactions between endometriotic cells and macrophages. Quantitative real-time PCR (qRT-PCR) and Western blot experiments were employed to detect phosphatase and tensin homolog (PTEN) expression. Glucose consumption, lactate production, extracellular acidification rate, and oxygen consumption rate levels were used to assess cellular glycolytic capacity. The interaction between conditioned media from ectopic endometrial stromal cells (EESCs) and macrophages was investigated through co-culture experiments. The expression of M2 macrophage marker proteins and inflammatory factors was detected via qRT-PCR, immunofluorescence staining, and enzyme-linked immunosorbent assay. Cellular functions were evaluated using Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine (EdU), and wound healing assays. We found that PTEN deficiency promoted the glycolytic activity of EESCs. Simultaneously, it significantly promoted the macrophages' polarization toward the M2 phenotype, demonstrated by increased expression of M2 markers (differentiation 206 (CD206), CD163, and (C-C motif) ligand 22 (CCL22)). Further studies revealed that PTEN-deficient EESCs increased the level of CCL2 via promoting glycolytic activity, which was reversed by glycolytic inhibitor. Moreover, lactate and conditioned media from overexpressed CCL2 EESCs facilitated M2 polarization of macrophages, while 2-deoxy-d-glucose reversed the promoting effect. Furthermore, lactate-facilitated macrophages promoted the proliferation and migration abilities of EESCs. PTEN deficiency induces M2 macrophage polarization by promoting glycolytic activity in EESCs, which deepens the knowledge of the pathophysiology of endometriosis and provides novel insights into its treatment.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"640-650"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nirvay Sah, Claire Stenhouse, Katherine M Halloran, Robyn M Moses, Makenzie G Newton, Heewon Seo, Joe W Cain, Carli M Lefevre, Gregory A Johnson, Guoyao Wu, Fuller W Bazer
{"title":"Effect of gestational age and fetal sex on metabolism of creatine by uteri, placentae, and fetuses of pigs†.","authors":"Nirvay Sah, Claire Stenhouse, Katherine M Halloran, Robyn M Moses, Makenzie G Newton, Heewon Seo, Joe W Cain, Carli M Lefevre, Gregory A Johnson, Guoyao Wu, Fuller W Bazer","doi":"10.1093/biolre/ioaf015","DOIUrl":"10.1093/biolre/ioaf015","url":null,"abstract":"<p><p>The creatine (Cr) biosynthesis pathway buffers adenosine triphosphate in metabolically active tissues. We investigated whether sex of fetus and day of gestation influence Cr in endometrial and conceptus tissues from gilts on days 60 and 90 (n = 6 gilts/day) of gestation. Uterine and conceptus tissues associated with one male and one female fetus from each gilt were analyzed for creatine, messenger RNAs (mRNAs), and proteins for Cr biosynthesis. Total Cr decreased in amniotic fluid but increased in allantoic fluid between days 60 and 90 of gestation for male (P < 0.05) but not for female fetuses (P > 0.05). Endometrial expression of creatine kinase, muscle (CKM), creatine kinase mitochondrial type 1 (CKMT1), and solute carrier family 6, member 8 (SLC6A8) mRNAs increased (P < 0.05) between days 60 and 90 only for female fetuses. On day 60, expression of creatine kinase, brain (CKB) and CKMT1 mRNAs was greater (P < 0.05) for placentae of female than male fetuses. Livers of male fetuses had greater expression of arginine:glycine amidinotransferase (AGAT) and CKB than for females on day 60, while kidneys of female fetuses had greater expression of guanidinoacetate-N-methyltransferase (GAMT) than male fetuses on day 90 (P < 0.05). Localization of GAMT, CKB, CKMT1, and SLC6A8 proteins to uterine and chorionic epithelium was not influenced by gestational age or fetal sex. Arginine-glycine amidinotransferase localized to fetal kidneys and appeared greater on day 90 than on day 60 in both sexes. Thus, expression of the creatine-creatine kinase-phosphocreatine system at the uterine-conceptus interface is affected by gestational age and fetal sex to influence energy homeostasis in pigs.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"728-742"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of introducing somatic mitochondria into an early embryo on zygotic gene activation†.","authors":"Yoshihiro Hayashi, Hanako Bai, Masashi Takahashi, Tomohiro Mitani, Manabu Kawahara","doi":"10.1093/biolre/ioaf010","DOIUrl":"10.1093/biolre/ioaf010","url":null,"abstract":"<p><p>Unlike differentiated somatic cells, which possess elongated mitochondria, undifferentiated cells, such as those of preimplantation embryos, possess round, immature mitochondria. Mitochondrial morphology changes dynamically during cell differentiation in a process called mitochondrial maturation. The significance of the alignment between cell differentiation and mitochondrial maturity in preimplantation development remains unclear. In this study, we analyzed mouse embryos into which liver-derived somatic mitochondria were introduced (SM-embryos). Most SM-embryos were arrested at the two-cell stage. Some of the introduced somatic mitochondria became round, while others remained elongated and large. RNA-sequencing revealed a disruption of both minor and major zygotic gene activation (ZGA) in SM-embryos. Minor ZGA did not terminate before major ZGA, and the onset of major ZGA was inhibited, as shown by histone modification analyses of histone H3 lysine 4 trimethylation and histone H3 lysine 27 acetylation. Further analysis of metabolites involved in histone modification regulation in SM-embryos showed a significantly lower NAD+/NADH ratio in SM-embryos than in control embryos. Additionally, the mitochondrial membrane potential, an indicator of mitochondrial function, was lower in SM-embryos than in control embryos. Our results demonstrated that introducing somatic mitochondria into an embryo induces mitochondrial dysfunction, thereby disrupting metabolite production, leading to a disruption in ZGA and inducing developmental arrest. Our findings reveal that the alignment between cell differentiation and mitochondrial maturity is essential for early embryonic development.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"614-627"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rhasaan T M Bovell, Pierre Comizzoli, Jennifer B Nagashima, Jenny Santiestevan, Adrienne E Crosier, Ned J Place
{"title":"Anti-Müllerian hormone concentration measured before gonadotropin stimulation is associated with quality of subsequent ovarian response in the cheetah (Acinonyx jubatus) and domestic cat (Felis catus)†.","authors":"Rhasaan T M Bovell, Pierre Comizzoli, Jennifer B Nagashima, Jenny Santiestevan, Adrienne E Crosier, Ned J Place","doi":"10.1093/biolre/ioaf025","DOIUrl":"10.1093/biolre/ioaf025","url":null,"abstract":"<p><p>Relationships between anti-Müllerian hormone concentrations and subsequent ovarian stimulation outcomes have been demonstrated in several mammalian species, but comprehensive reports are lacking in felids. Our objective was to characterize relationships between anti-Müllerian hormone concentrations and responses to exogenous gonadotropin stimulation in cheetahs and domestic cats. Blood samples collected before stimulation were used to measure serum anti-Müllerian hormone concentrations, which were compared to post-stimulation outcomes, including counts of retrievable oocytes or ovulation sites, oocyte quality, embryonic cleavage after in vitro fertilization, and progestogen concentrations. Anti-Müllerian hormone concentrations were also compared to outcomes in domestic cats induced to ovulate by mechanical stimulation of the vagina and cervix (simulated coitus). Greater anti-Müllerian hormone concentrations were associated with greater ovulatory response, progestogen production, and embryonic cleavage success among gonadotropin-treated cheetahs, and with greater ovulatory response among gonadotropin-treated domestic cats. Associations were moderated by age, with anti-Müllerian hormone concentration generally a greater determinant of these outcomes in older animals. Anti-Müllerian hormone concentrations alone could distinguish domestic cats with high and low ovulatory responses to exogenous hormones. However, this marker was unrelated to ovulatory response in domestic cats after simulated coitus. These results demonstrate the potential for anti-Müllerian hormone concentrations to predict responses of cheetahs and domestic cats to ovarian stimulation treatment commonly used in assisted reproductive technologies. Associations between anti-Müllerian hormone concentrations and ovarian stimulation outcomes in these species might reflect relationships between anti-Müllerian hormone concentration and antral follicle count or oocyte/embryo cellular function, as reported in other mammals; however, this remains to be tested.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"754-766"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariano Colon-Caraballo, Serena R Russell, Kristin M Myers, Mala Mahendroo
{"title":"Collagen turnover during cervical remodeling involves both intracellular and extracellular collagen degradation pathways†.","authors":"Mariano Colon-Caraballo, Serena R Russell, Kristin M Myers, Mala Mahendroo","doi":"10.1093/biolre/ioaf012","DOIUrl":"10.1093/biolre/ioaf012","url":null,"abstract":"<p><p>Reproductive success requires accurately timed remodeling of the cervix to orchestrate the maintenance of pregnancy, the process of labor, and birth. Prior work in mice established that a combination of continuous turnover of fibrillar collagen and reduced formation of collagen cross-links allows for the gradual increase in tissue compliance and delivery of the fetus during labor. However, the mechanism for continuous collagen degradation to ensure turnover during cervical remodeling is still unknown. This study demonstrates the functional role of extracellular and intracellular collagen degradative pathways in two different settings of cervical remodeling: physiological term remodeling and inflammation-mediated premature remodeling. Extracellular collagen degradation is achieved by the activity of fibroblast-derived matrix metalloproteases MMP14, MMP2, and fibroblast activation protein (FAP). In parallel, we demonstrate the function of an intracellular collagen degradative pathway in fibroblast cells mediated by the collagen endocytic mannose receptor type-2 (MRC2). These pathways appear to be functionally redundant as loss of MRC2 does not obstruct collagen turnover or cervical function in pregnancy. While both extracellular and intracellular pathways are also utilized in inflammation-mediated premature cervical remodeling, the extracellular collagen degradation pathway uniquely employs fibroblast and immune-cell-derived proteases. In sum, these findings identify the dual utilization of two distinct degradative pathways as a failsafe mechanism to achieve continuous collagen turnover in the cervix, thereby allowing dynamic shifts in cervical tissue mechanics and function.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"709-727"},"PeriodicalIF":3.1,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}