{"title":"Effects of oocyte growth on development and histone modification during preimplantation in mouse parthenogenetic embryos.","authors":"Wataru Yamazaki, Misako Higashiya, Yuriko Fujii, Megumi Yano, Takanori Oikawa, Shinsuke Seki","doi":"10.1093/biolre/ioaf114","DOIUrl":"https://doi.org/10.1093/biolre/ioaf114","url":null,"abstract":"<p><p>Parthenogenetic embryos have two sets of genomes derived from fully grown oocytes (fg/fg) and are embryonically lethal by embryonic day 9.5 in mice. During growth phase, oocytes undergo epigenetic modifications including DNA methylation and histone modification. A previous study demonstrated that parthenogenetic embryos derived from nongrowing oocytes (ng/ng) were arrested at the eight-cell stage. However, effects of growing-stage oocyte genomes (gr/gr) on dynamics of development and histone modifications in parthenogenetic embryos have not been fully elucidated. Here, we investigated the development and dynamics of global histone modifications during preimplantation in mouse parthenogenetic embryos derived from ng and gr oocytes. Severe developmental arrest at the two-cell stage was observed in ng/ng embryos. Developmental competence in gr/gr embryos gradually improved depending on donor oocyte diameter. Global histone modification levels of H3K4/9me3 were significantly decreased from early-to-late two-cell stages in gr/gr and fg/fg embryos, but were maintained in ng/ng embryos. We also investigated the global zygotic de novo transcriptional activity; ng/ng embryos at the one- and two-cell stages showed comparable activity to that of fg/fg embryos. However, the transcript level of zygotic genome activation-related gene, Zscan4d, was significantly low in ng/ng embryos at the late two-cell stage. This study describes the characteristics of global histone modifications during early preimplantation in ng/ng and gr/gr embryos, suggesting that oocyte genomes during early growth phase lead to developmental incompetence and disrupted histone modifications during preimplantation in parthenogenetic embryos.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075790","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}
Rylie S Noland, Bethany K Redel, Marissa G LaMartina, Randall S Prather, Paula R Chen
{"title":"Transcriptional profiling reveals upregulation of p53 signaling in porcine embryos produced in vitro†.","authors":"Rylie S Noland, Bethany K Redel, Marissa G LaMartina, Randall S Prather, Paula R Chen","doi":"10.1093/biolre/ioaf113","DOIUrl":"https://doi.org/10.1093/biolre/ioaf113","url":null,"abstract":"<p><p>Although advances in the porcine embryo culture system have been achieved, the artificial environment continues to be stressful for the embryos which hinders development. To identify areas of improvement, transcriptional profiling was performed on in vivo-derived (IVV), in vivo-matured and in vitro-cultured (IVC), and in vitro-matured and cultured (IVMC) porcine blastocyst-stage embryos. Numerous differentially expressed genes were detected between IVC vs IVV (489 downregulated, 701 upregulated), IVMC vs IVV (435 downregulated, 1124 upregulated), and IVMC vs IVC (32 downregulated, 168 upregulated). Moreover, KEGG pathway analysis revealed upregulated pathways related to amino acid biosynthesis and metabolism in IVC and IVMC embryos compared to IVV. Interestingly, IVMC embryos demonstrated specific upregulation of the p53 signaling pathway compared to IVV embryos. Therefore, IVMC embryos were cultured with different p53 inhibitors, pifithrin-α (PFT-α), pifithrin-β (PFT-β), or pifithrin-μ (PFT-μ), to determine if the stress response could be suppressed to improve development to the blastocyst stage. Culture with 50 μM PFT-α improved development to the blastocyst stage (P < 0.05), but total cell number and transcript abundance of p53 target genes remained unaltered. No difference in development was observed after culturing embryos with PFT-β, and embryos cultured with pifithrin-μ (PFT-μ) demonstrated decreased development. Lastly, two embryo transfers of embryos cultured with PFT-α demonstrated that the inhibitor did not disrupt developmental competence of in vitro-produced embryos. Overall, addition of PFT-α in the porcine embryo culture medium was shown to have beneficial effects on development and is suitable for generating live pigs with this system.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075734","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}
Wenlong Li, Shanshan Zhang, Shenglong Ye, Xiao Fang, Xin Yu, Xiaoye Wang, Yeling Ma, Yan-Ling Wang
{"title":"Evaluation of optimal trophoblastic models to mimic uterine vessel remodeling in human pregnancy†.","authors":"Wenlong Li, Shanshan Zhang, Shenglong Ye, Xiao Fang, Xin Yu, Xiaoye Wang, Yeling Ma, Yan-Ling Wang","doi":"10.1093/biolre/ioaf108","DOIUrl":"https://doi.org/10.1093/biolre/ioaf108","url":null,"abstract":"<p><p>During human pregnancy, a certain proportion of endothelial cells in uterine spiral arteries are replaced by placental extravillous trophoblasts (EVTs). This process is a pivotal step in spiral artery remodeling (SAR), ensuring the adequate supply of oxygen and nutrients to the fetus. Given the ethical constraints and the lack of suitable in vivo animal models, developing ideal in vitro models is crucial for investigating this cellular event. Therefore, it is imperative to evaluate key trophoblastic properties to optimize the in vitro model and replicate the in vivo context of SAR. In this study, we refined a three-dimensional co-culture system involving human trophoblast cells and tubular structure formed by human umbilical vein endothelial cells (HUVECs), allowing for dynamical monitoring of cell behaviors. Using this model, we conducted a comparative analysis of vascular remodeling capabilities among primary EVTs and various trophoblast cell lines. Meanwhile, we examined the expression profiles of multiple SAR-associated genes in trophoblast cells. The correlation between molecular characteristics and vascular remodeling performance was statistically analyzed using a comprehensive scoring system. Our findings highlight the critical roles of EVT-derived NCAM1, ITGB3, ITGAV, and JAG1 in vascular remodeling. Furthermore, JEG-3 and human trophoblast stem cell (hTSC)-derived EVT cells demonstrate significant advantages as optimal models for mimicking primary EVTs in vitro, thereby facilitating investigations into SAR. Consequently, we propose an evaluation framework to assess key attributes of trophoblast cell lines that enable them to accurately represent EVT behaviors in SAR. This study establishes a robust foundation for future exploration of the molecular mechanisms underlying human SAR.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967080","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}
Mahiru Kawano, Jennifer McKey, Iordan S Batchvarov, Blanche Capel
{"title":"Granulosa cell death is a significant contributor to DNA-damaging chemotherapy-induced ovarian insufficiency†.","authors":"Mahiru Kawano, Jennifer McKey, Iordan S Batchvarov, Blanche Capel","doi":"10.1093/biolre/ioae181","DOIUrl":"10.1093/biolre/ioae181","url":null,"abstract":"<p><p>Typically, DNA-damaging chemotherapy (CTx) regimens have a gonadotoxic effect and cause premature ovarian insufficiency (POI), characterized by infertility and estrogen deficiency. However, whether loss of granulosa cells killed directly by CTx contributes significantly to POI has not been determined. To address this issue, we used a previously established mouse model of CTx-induced POI. The alkylating drugs Busulfan (8.75 mg/kg) and Cyclophosphamide (100 mg/kg) were administered to 8-week-old FVB female mice by intraperitoneal (IP) injection three times at 48-h intervals, after which ovarian tissues were harvested and examined by immunofluorescence. The number of primordial follicles was significantly reduced at day (d)6, whereas the number of growing follicles was relatively unchanged. CTx led to DNA double strand breaks in both oocytes and granulosa cells based on the presence of γH2AX foci. However, markers of apoptosis predominantly labeled granulosa cells in growing follicles. We next examined the effect of inhibiting apoptosis in growing granulosa cells by generating Bak-/-Baxfx/fx; Cyp19a1Cre transgenic mice. On d10 after the first CTx, Bak-/-Baxfx/fx; Cyp19a1Cre ovaries had fewer apoptotic granulosa cells and more surviving follicles than controls. Furthermore, Bak-/-Baxfx/fx; Cyp19a1Cre mice showed better fertility than controls after CTx. Our data suggest that granulosa cell death is a significant contributor to follicle depletion and fertility loss after Cyclophosphamide and Busulfan.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"906-915"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771330","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}
Kimberly M Davenport, Makenzie T Lowke, M Sofia Ortega, Andrew M Kelleher, Wesley C Warren, Thomas E Spencer
{"title":"Single cell multiome analysis of the bovine placenta identifies gene regulatory networks in trophoblast differentiation†.","authors":"Kimberly M Davenport, Makenzie T Lowke, M Sofia Ortega, Andrew M Kelleher, Wesley C Warren, Thomas E Spencer","doi":"10.1093/biolre/ioaf036","DOIUrl":"10.1093/biolre/ioaf036","url":null,"abstract":"<p><p>A central determinant of successful reproduction is pregnancy establishment and maintenance that relies on proper development of the conceptus (embryo/fetus and associated extraembryonic membranes including the placenta). Pregnancy loss in cattle can be caused by inadequate development and differentiation of the placenta. However, the cellular and molecular mechanisms regulating bovine placenta development and, particularly, trophoblast differentiation are not well understood. Recent single-cell RNA-seq analyses revealed dynamic changes in cell populations and gene expression patterns during bovine placental development. Here, the chromatin accessibility landscape across diverse cell populations was determined in the developing (Day 40) and mature (Day 170) bovine placenta using the 10X Genomics multiome (snRNA-seq and snATAC-seq) platform. Analyses revealed distinct trophoblast, mesenchyme, endothelial, immune, and epithelial cell populations characterized by unique gene expression and chromatin accessibility signatures. ATAC-seq peaks defined open chromatin regions, facilitating the identification of transcription factor binding sites and candidate gene regulatory networks involved with trophoblast differentiation. Several transcription factors, known for their involvement in trophoblast differentiation in other mammalian species, were identified as candidate regulators of uninucleate to binucleate trophoblast differentiation. This study adds to our foundational understanding of gene regulation and expression in the placenta, offering insights into the mechanisms governing pregnancy loss in cattle.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"955-968"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482157","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}
Jeanette V Bishop, Aydin Guzeloglu, Tom Scheller, Joshua J Docheff, Carolina L Gonzalez-Berrios, Hana Van Campen, Terry M Nett, Abigail L Zezeski, Thomas W Geary, William W Thatcher, Thomas R Hansen
{"title":"Early identification of bovine pregnancy status and embryonic mortality†.","authors":"Jeanette V Bishop, Aydin Guzeloglu, Tom Scheller, Joshua J Docheff, Carolina L Gonzalez-Berrios, Hana Van Campen, Terry M Nett, Abigail L Zezeski, Thomas W Geary, William W Thatcher, Thomas R Hansen","doi":"10.1093/biolre/ioaf066","DOIUrl":"10.1093/biolre/ioaf066","url":null,"abstract":"<p><p>Bovine interferon-tau (bIFNT) is produced by the trophectoderm cells in the bovine conceptus as early as Day 12 following fertilization. It was hypothesized that IFNT detection in blood, milk, and/or cervical secretions could be used to diagnose pregnancy in lactating cows. Recombinant bovine (rb) IFNT was generated to produce goat and rabbit anti-rbIFNT polyclonal antibodies, and an enzyme-linked immunosorbent assay (ELISA) was developed for bIFNT using these reagents. The IFNT ELISA did not cross-react with other type I or II IFNs and had a limit of detection of 50-100 pg/ml. The IFNT ELISA detected IFNT in external ostium (os) cervical swabs from Days 15 to 25 post-AI, but did not detect IFNT in serum, plasma, or milk. The time for most accurately detecting IFNT in cervical fluid was Days 16-19 after AI. A custom bovine swab device used to collect cervical secretions reduced false-negative rates to 5.5% (94.5% sensitivity) in dairy cows on Day 17 and 0% to 3.4% (100% and 96.6% sensitivity) in beef cows on Days 18 or 16, respectively. In summary, the detection of IFNT in cervical fluid by ELISA provides an accurate indication of pregnancy status in lactating dairy cows. Early identification of the non-pregnant cow allows re-insemination on Day 21 compared to waiting until ultrasound (US) on Day ~32-39. In addition, the detection of IFNT on Day 17 followed by the loss of pregnancy detected by US on Day 32 provides a novel research tool for studying pregnancy loss caused by embryonic mortality.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"981-995"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741863","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}
{"title":"Suppression of FOXO3 by BMP signaling contribute to the different primordial germ cell proliferation between layers and broilers†.","authors":"Yuxiao Ma, Lu Meng, Jiahui Wei, Wenhui Wu, Yun Zhang, Xuzhao Wang, Xiaotong Guo, Feiyi Wang, Yong Mao, Guiyu Zhu","doi":"10.1093/biolre/ioaf037","DOIUrl":"10.1093/biolre/ioaf037","url":null,"abstract":"<p><p>Although all domestic chicken breeds originate from their wild relatives, the red junglefowl, they have been selectively bred for high yields in either egg or meat production, or both. Some breeds are highly efficient in egg production, while others perform poorly, due to long-term selection aimed for different purposes. Female primordial germ cells (PGCs) are the precursors of eggs and the population size of PGCs will ultimately determine ovarian reserve of hens. In this study, we observed that the layers exhibit greater proliferation capacity and a higher number of PGCs in the gonad compared to the broilers before meiosis. By comparing the PGC transcriptomes between layers and broilers, we identified potential genes that regulate cell proliferation. We further confirmed that FOXO3 expression is higher in broilers, where it inhibits the PGC proliferation both in vivo and in vitro. However, in layers, the upstream BMP signaling stimulate the phosphorylation of AKT and suppress FOXO3 activity. Consequently, the elevated BMP signaling and reduced FOXO3 co-operatively promote more robust PGC proliferation in layers compared to broilers and result in a greater number of PGCs in layers. Our data not only reveal molecular mechanisms underlying PGC growth in the ovary, but also provide new clues to improve the laying performance in chicken.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"942-954"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482159","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":"IDO can improve ovarian function in premature ovarian insufficiency via AhR and regulatory T cells.","authors":"Anchun Hu, Yanli Mu, Guanyou Huang, Zhongan Wang, Shuyun Zhao, Wenchi Xu, Panpan Chen, Xin Guo","doi":"10.1093/biolre/ioaf102","DOIUrl":"https://doi.org/10.1093/biolre/ioaf102","url":null,"abstract":"<p><strong>Background: </strong>Premature ovarian insufficiency (POI) is the loss of ovarian function among women <40 years of age, and immune disorders play a critical role in POI development. Indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan metabolism via the kynurenine pathway and plays a key role in preventing and treating immune-related diseases.</p><p><strong>Methods: </strong>Human ovarian granulosa cells (hGCs) were collected via the density gradient method, pZP3 was used to establish an immune POI mouse model, and an AAV vector carrying IDO1 (IDO-AAV) was injected into mouse ovaries to induce IDO overexpression. Ovarian function was measured by the oestrous cycle, serum AMH concentration, degree of ovarian fibrosis and number of follicles.</p><p><strong>Findings: </strong>IDO protein levels and mRNA expression in hGCs were lower in the POI group than in the control group (P < 0.05). Both the ovarian function and IDO levels in the POI + Water group and the POI + Glu group were significantly lower than those in the control group. In POI model mice injected with IDO-AAV, ovarian function and the CD4 + CD25 + Foxp3+ regulatory T (Treg) cell proportion were increased compared with those in mice injected with the natural control AAV. The FoxP3 mRNA expression level in Treg cells was positively correlated with the IDO mRNA expression level, whereas the RORγt mRNA expression level in Th17 cells was negatively correlated with the IDO mRNA expression level, further suggesting that IDO may be related to Treg and Th17 cells through AhR and subsequently regulate immunity and ovarian function.</p><p><strong>Conclusion: </strong>Increasing ovarian IDO levels in POI mice improved ovarian function.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975962","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}
Zian Liao, Tessa E Steenwinkel, Bruno Moscoso, Ernesto Salas, Bethany K Patton, Amanda Rodriguez, Anna Malovannaya, Stephanie A Pangas
{"title":"Disruption of oocyte SUMOylation impacts critical regulatory processes during folliculogenesis in mice†.","authors":"Zian Liao, Tessa E Steenwinkel, Bruno Moscoso, Ernesto Salas, Bethany K Patton, Amanda Rodriguez, Anna Malovannaya, Stephanie A Pangas","doi":"10.1093/biolre/ioaf035","DOIUrl":"10.1093/biolre/ioaf035","url":null,"abstract":"<p><p>The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may drive the premature follicle loss phenotype. Label-free mass spectrometry results showed that 238 proteins were significantly altered more than 2-fold (p < 0.05). Proteins upregulated in the Ube2i conditional knockout ovaries included those involved in mRNA splicing and WNT signaling, while those downregulated were related to metabolism, mitochondria, and the maternal effect proteins NLRP2 and NLRP9B. The majority of differentially expressed proteins showed no change by transcriptome analysis, indicating protein level regulation and revealing potential SUMOylation targets with necessary roles in oocyte and follicle development.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"932-941"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466525","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}
Jiří Bezdíček, Jana Sekaninová, Martina Janků, Alexander Makarevič, Lenka Luhová, Linda Dujíčková, Marek Petřivalský
{"title":"Reactive oxygen and nitrogen species: multifaceted regulators of ovarian activity†.","authors":"Jiří Bezdíček, Jana Sekaninová, Martina Janků, Alexander Makarevič, Lenka Luhová, Linda Dujíčková, Marek Petřivalský","doi":"10.1093/biolre/ioaf032","DOIUrl":"10.1093/biolre/ioaf032","url":null,"abstract":"<p><p>Reactive oxygen and nitrogen species are essential components of diverse intracellular signaling pathways. In addition to their involvement in apoptosis, reactive oxygen and nitrogen species are crucial in the regulation of multiple developmental and physiological processes. This review aims to summarize their role in the regulation of key ovarian stages: ovulation, maturation and postovulatory ageing of the oocyte, and the formation and regression of the corpus luteum. At the cellular level, a mild increase in reactive oxygen and nitrogen species is associated with the initiation of a number of regulatory mechanisms, which might be suppressed by increased activity of the antioxidant system. Moreover, a mild increase in reactive oxygen and nitrogen species has been linked to the control of mitochondrial biogenesis and abundance in response to increased cellular energy demands. Thus, reactive oxygen and nitrogen species should also be perceived in terms of their positive role in cellular signaling. On the other hand, an uncontrolled increase in reactive oxygen species production or strong down-regulation of the antioxidant system results in oxidative stress and damage of cellular components associated with ovarian pathologies and ageing. Similarly, the disturbance of signaling functions of reactive nitrogen species caused by dysregulation of nitric oxide production by nitric oxide synthases in ovarian tissues interferes with the proper regulation of physiological processes in the ovary.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"789-806"},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398086","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}