Reproduction最新文献

{"title":"Diminazene Aceturate, an ACE2 activator, ameliorates testicular injury in diet-induced obese mice.","authors":"Xiaofeng Yue, Rui Yin, Liling Wu, Jinjin Li, Jianwu Wang, Benhuang Yan, Lingyong Dai, Chongxing Shen, Yi Zhi, Shengquan Huang, Ling Wan, Jigao Yang, Weibing Li","doi":"10.1530/REP-24-0242","DOIUrl":"https://doi.org/10.1530/REP-24-0242","url":null,"abstract":"<p><p>DIZE improved obesity and metabolic disturbances in DIO mice. An increase of sperm account and motility, along with improved morphology and increased male fertility was observed after DIZE treatment. Both serum and intratesticular testosterone levels showed an increase. Moreover, ACE2/Ang 1-7/MasR protein levels in the testes were restored, which inhibited germ cells apoptosis, lipid accumulation, and oxidative stress, and elevated testosterone synthesis-related proteins. However, the MasR antagonist A779 partially counteracted the improving effects of DIZE on metabolism and the testes of DIO mice. Conclusion: DIZE treatment has protective effects against obesity-induced testicular injury by activating ACE2/Ang 1-7/MasR axis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034114","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}

{"title":"Key glycometabolism during oocyte maturation and early embryonic development.","authors":"Yichuan Zhang, Tianjie Li, Yibo Wang, Yang Yu","doi":"10.1530/REP-24-0275","DOIUrl":"10.1530/REP-24-0275","url":null,"abstract":"<p><p>In recent decades, it has become increasingly clear that mammalian gametes and early embryos are highly sensitive to metabolic substrates. With advances in single-cell sequencing, metabolomics, and bioinformatics, we now recognize that metabolic pathways not only meet cellular energy demands but also play a critical role in cell proliferation, differentiation, and fate determination. Investigating metabolic processes during oocyte maturation and early embryonic development is thus essential to advancing reproductive medicine and embryology. This review highlights the intricate metabolic pathways, particularly glucose metabolism, that drive the transition from oocyte to embryo. These processes involve a complex interaction of signaling pathways, nutrient availability, and environmental factors, with glucose metabolism not only providing essential energy but also offering a variety of metabolic substrates and intermediates that regulate developmental events, influence cell signaling, and impact epigenetic modifications. This article emphasizes that future research will focus on regulating maternal metabolic environments and non-invasive metabolic monitoring of embryonic systems, particularly glucose metabolism, with promising opportunities to improve embryo selection and personalized assisted reproductive technologies, ultimately enhancing fertility treatment outcomes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024454","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}

{"title":"Increased plugging latency in cycling epiERα-/- (Esr1f/-Wnt7aCre/+) mice.","authors":"Jonathan Matthew Hancock, Taylor Elijah Martin, Zidao Wang, Jackson Kyle Sundgren, Xiaoqin Ye","doi":"10.1530/REP-24-0447","DOIUrl":"10.1530/REP-24-0447","url":null,"abstract":"<p><p>Wnt7a-Cre is a commonly used for generating uterine epithelial conditional knockout mice, such as epiERα-/- (Esr1f/-Wnt7aCre/+) and epiPR-/- (Pgrf/-Wnt7aCre/+). We noticed that epiERα-/- females, but not epiPR-/- females, have prolonged plugging latency, which is the duration between continuous cohabitation and detection of the first vaginal plug (a sign of mating). Mating occurs in proestrus and/or estrus stages of the estrous cycle. Vaginal cytology detected estrous cyclicity in all mice examined, although epiERα-/- mice had leukocyte dominant vaginal cytology throughout the estrous cycle and their estrous cyclicity appeared less regular. Estrous cyclicity and mating activity are regulated by the hypothalamic-pituitary-ovarian axis, in which kisspeptin plays essential roles. ERα and PR are expressed in rostral periventricular area of the ventricle (RP3V) and arcuate nucleus (ARC) kisspeptin neurons in the hypothalamus. It has been reported that Esr1f/fKiss1-Cre mice lack estrous cyclicity, while Pgrf/fKiss1-Cre mice have normal estrous cyclicity at 2 months old, and Wnt7a is highly expressed in ARC. The prolonged plugging latency in epiERα-/- mice could be contributed by the deletion of ERα in Wnt7A-positive cells in ARC. Wnt7a-Cre was also used to generate uterine epithelial RhoA deficient mice, epiRhoA-/- (RhoAf/-Wnt7aCre/+). However, both female and male RhoAf/-Wnt7aCre/+ mice had hydrocephalus and died within a few weeks old. Our observations of increased plugging latency in epiERα-/- mice and hydrocephalus in RhoAf/-Wnt7aCre/+ mice exemplify unintended neuronal gene deletion using Wnt7a-Cre for uterine epithelial-specific gene deletion.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047442","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}

{"title":"ERα phosphorylated at Ser309 participates in regulating luminal environment of efferent ducts and epididymis in mice.","authors":"Jinhua Wei, Pang Cheng, Binfang Ma, Xiao Feng, Junxian Ma, Jie Zhao, Yanqiu Zhao, Zhen Li","doi":"10.1530/REP-24-0109","DOIUrl":"https://doi.org/10.1530/REP-24-0109","url":null,"abstract":"<p><p>The estrogen receptor alpha (ERα) plays an important role in male reproduction and fertility. Its activity is modulated by phosphorylation of multiple amino acid residues. The ERα phosphorylated at serine 305 (S305) in human cells (homologous with serine 309 in mice) induces ligand-independent ERα activity. Here, we studied the effect of ERα phosphorylation at S309 on the reproductive function of male mice. ERα309 (p.S309A, ERαS309A) knock-in (KI) mice were generated by homologous recombination in mouse embryonic stem (ES) cells. The ERαS309A KI males were subfertile with decreased sperm motility, dilated lumen and thinned epithelium of efferent ducts. Ultrastructural observation showed that the area of endocytic vesicles and lysosomes in the non-ciliated cells, and the number of cilia in the cilia cells were significantly reduced in the efferent ducts of ERαS309A mice. The pH value of epididymal fluid was significantly higher in all regions of epididymis in the ERαS309A KI mice. Moreover, the expression of aquaporin 9 (AQP9) in the efferent ducts and carbonic anhydrase XII (CAR12) in the epididymis was decreased in ERαS309A KI mice. The results indicate that ERα phosphorylated at Ser309 participates in maintaining the unique luminal milieu by regulating the expression of critical regulators of fluid/ion transport in efferent ducts and epididymis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954137","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}

{"title":"CD40 Ligand and CD40: Expression, Regulation, and Function at the Maternal-Conceptus Interface in Pigs.","authors":"Inkyu Yoo, Soohyung Lee, Yugyeong Cheon, Tae Sub Park, Hakhyun Ka","doi":"10.1530/REP-24-0396","DOIUrl":"10.1530/REP-24-0396","url":null,"abstract":"<p><p>To successfully establish and maintain pregnancy in pigs, a variety of factors must work together at the maternal-conceptus interface to form an immune environment appropriate for both the mother and the conceptus. Our transcriptomics study has shown that cluster of differentiation ligand 40 (CD40L) and its receptor CD40, which are known to play important roles in regulating cell- and antibody-mediated immunity, are expressed in the endometrium during early pregnancy. However, the roles of the CD40L and CD40 signaling system are not well understood. Therefore, we determined the expression, regulation, and function of CD40L and CD40 at the maternal-conceptus interface in pigs. The endometrium expressed CD40L and CD40 mRNAs at the greatest levels on Day 15 of pregnancy. The CD40L protein was localized predominantly to luminal epithelial cells on Day 15 of pregnancy, and the CD40 protein was found in luminal epithelial, stromal, and vascular endothelial cells in the endometrium during pregnancy. During early pregnancy, the conceptus expressed CD40 but not CD40L, and chorioallantoic tissues during mid- to late pregnancy expressed both CD40L and CD40. Interferon-γ increased the expression of CD40L and CD40 in endometrial explants. CD40L increased the migration, but not the proliferation, of cultured porcine endometrial endothelial (pENDO) cells in vitro. In addition, CD40L affected the expression of genes related to angiogenesis, cell adhesion, chemokines, and immunity in pENDO cells. These results suggest that the CD40L-CD40 system might play an important role in the establishment of pregnancy in pigs by regulating endometrial endothelial cell function during the implantation period.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060457","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}

{"title":"Comparison of clinical artificial oocyte activation protocols on mouse egg activation and embryo development.","authors":"Lucas N González, Valeria Sulzyk, Patricia S Cuasnicú, Débora J Cohen","doi":"10.1530/REP-24-0387","DOIUrl":"https://doi.org/10.1530/REP-24-0387","url":null,"abstract":"<p><p>Artificial oocyte activation (AOA) with Ca2+ ionophores is an experimental procedure that benefits patients who fail to obtain fertilized eggs. However, the impact of non-physiological Ca2+ increases on cellular events involved in egg-embryo transition and early development remains poorly understood. Using the mouse model, this study compares common Ca2+ ionophore protocols applied in clinical practice - one or two exposures to A23187 or a single exposure to ionomycin - focusing on embryonic development and cellular events associated with egg activation. All groups of ionophore-activated eggs exhibit lower levels of first mitotic division compared to those activated by spermatozoa or SrCl2, attributable to the variations in Ca2+ dynamics during activation. At the cellular level, these eggs presented defects in spindle morphology and chromosome segregation during meiosis progression, associated with lower levels of cytoplasmic ATP, without changes in reactive oxygen species (ROS). These findings highlight the importance of optimizing Ca2+ management in AOA protocols.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010428","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}

{"title":"NPR3 is regulated by gonadotropins and modulates bovine cumulus cell expansion.","authors":"Matheus P De Cesaro, Mariana P de Macedo, Paulo R A da Rosa, Joabel T Dos Santos, Ricardo D Mea, Janduí E da Nóbrega, Raj Duggavathi, Bernardo G Gasperin, Paulo Bayard D Gonçalves, Vilceu Bordignon","doi":"10.1530/REP-24-0187","DOIUrl":"10.1530/REP-24-0187","url":null,"abstract":"<p><strong>In brief: </strong>The natriuretic peptide system, particularly the C-type natriuretic peptide (CNP) and natriuretic peptide receptor 2 (NPR2), plays a critical role in regulating mammalian ovarian functions, including oocyte-cumulus cell communication and meiotic maturation. However, the contribution of natriuretic peptide receptor 3 (NPR3) to these processes has not been thoroughly investigated. Data from this study provide compelling evidence that NPR3 is involved in modulating gonadotropin signaling and regulating cumulus cell expansion in cattle.</p><p><strong>Abstract: </strong>The significant role of CNP and its receptor 2 (NPR2) in regulating oocyte meiotic maturation and facilitating communication between oocytes and surrounding cumulus cells has been well documented in various mammalian species including mice, cattle and swine. However, further investigation is needed to ascertain whether natriuretic peptide receptors (NPRs) are involved in regulating other essential ovarian functions. Hence, this study aimed to explore the potential involvement of NPRs in the regulation of cumulus expansion and oocyte meiotic maturation in bovine cumulus-oocyte complexes (COCs). The findings revealed that NPR3 mRNA abundance was downregulated by follicle-stimulating hormone and luteinizing hormone in cumulus cells of bovine COCs during in vitro maturation (IVM), while NPR2 mRNA levels were not affected by gonadotropins. Inhibition of the epidermal growth factor receptor (EGFR) during IVM of COCs prevented the NPR3 mRNA downregulation induced by gonadotropins in cumulus cells. Additionally, treatment of COCs during IVM with an NPR3 agonist (cANP4-23) inhibited cumulus expansion induced by gonadotropins. This inhibitory effect was further intensified when COCs were cotreated with cANP4-23 and CNP. These findings provide robust evidence indicating that normal cumulus expansion in bovine COCs involves an inhibitory effect of gonadotropins on NPR3 mRNA expression, which is mediated via EGFR signaling. The study also provides evidence that CNP and NPR3 interact synergistically to regulate cumulus expansion in response to gonadotropins.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506928","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}

{"title":"RGD peptide promotes follicle growth through integrins αvβ3/αvβ5 in three-dimensional culture.","authors":"Cassandra Matsushige, Kaelyn Kitazumi, Amanda Beaman, Marissa Miyagi, Michelle D Tallquist, Yukiko Yamazaki","doi":"10.1530/REP-24-0151","DOIUrl":"10.1530/REP-24-0151","url":null,"abstract":"<p><strong>In brief: </strong>Three-dimensional ovarian tissue culture is a unique model to define the effects of molecules on folliculogenesis. Using this model, we determined that RGD-integrin interaction plays a role in antrum formation and theca cell differentiation.</p><p><strong>Abstract: </strong>We recently developed a three-dimensional (3D) ovarian tissue culture system supported by bacterial-derived dextran hydrogel. Arg-Gly-Asp (RGD) is an extracellular matrix-derived triple peptide. Immature ovarian tissues cultured in RGD-modified dextran hydrogel significantly promoted antral follicle growth and oocyte quality compared with those cultured in dextran hydrogel alone. In this study, we examined the mechanism of follicle growth stimulated by RGD treatment in the 3D system. First, we detected that direct contact between RGD-modified dextran hydrogel and ovarian interstitial cells is necessary to promote antral follicle growth. Therefore, we hypothesized that RGD stimulates antral follicle growth through RGD-binding integrin receptors expressed in the interstitial cell mass. Using quantitative PCR (qPCR) and immunochemical staining, we identified that integrins ⍺vβ3 and ⍺v5 are predominantly expressed in the ovarian interstitial compartment. To assess the effect of RGD-integrin interaction on follicle growth, ovarian tissues were cultured with cilengitide (Ci), an inhibitor specific for ⍺vβ3 and ⍺vβ5. Ci treatment suppressed RGD-induced follicle growth and oocyte quality in a dose-dependent manner. When the interstitial cell aggregates were cultured with RGD, cell migration and theca-related gene expression were significantly upregulated. Ci treatment dramatically suppressed these RGD-induced activities. In coculturing the interstitial aggregate and secondary follicles with RGD, migrating cells formed the outermost cell layers around the follicles, like theca layers, which were totally blocked by Ci treatment. In conclusion, our results suggest that RGD stimulates theca cell differentiation in the ovarian interstitial cells through integrins ⍺vβ3 and ⍺v5 to promote antral follicle growth in our 3D system.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506929","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}

{"title":"TEAD3 and TEAD4 play overlapping role in bovine preimplantation development.","authors":"Haotian Yu, Yan Shi, Xiaotong Wu, Bingjie Hu, Hao Jin, Kassim Yassin, Tariq Iqbal, Omaima Mohamed Kandil, Esraa Aly Ismail, Huanan Wang, Shaohua Wang, Kun Zhang","doi":"10.1530/REP-24-0307","DOIUrl":"https://doi.org/10.1530/REP-24-0307","url":null,"abstract":"<p><p>During mammalian preimplantation development, the transition from morula to blastocyst is a critical biological event. This process involves polarization and initial specification of lineages, regulated by various transcription factors that have been extensively studied in mice. Our single-cell RNA sequencing analyses revealed that TEAD3 is specifically expressed in the trophectoderm cells of bovine preimplantation embryos, unlike in mice. The objective of this study is to determine the functional role of TEAD3 in bovine preimplantation development. While TEAD3 knockdown does not affect blastocyst formation in cattle, embryos fail to progress to the blastocyst stage when both TEAD3 and TEAD4, another member of the TEAD family, are disrupted using RNA interference and base editing techniques, respectively. This finding suggests a redundant role for TEAD3 and TEAD4 in preimplantation development in cattle. RNA sequencing analysis identified dysregulation of 215 genes, with 53 genes upregulated and 162 genes downregulated. Notably, we observed a reduction in the expression of trophectoderm-specifier genes KRT8, KRT18, and EZR, as well as HIPPO signaling pathway components. Immunofluorescence analysis further revealed that the protein expression levels of KRT8 and EZR were significantly decreased. Importantly, the initial expression of trophectoderm lineage-specific factors such as TFAP2C and GATA3, as well as the inner cell mass lineage-specific transcription factor OCT4, remained unaffected. This contrasts with the role of TEAD4 in directly regulating trophectoderm lineage specification in mice. Thus, our studies demonstrate that TEAD3 and TEAD4 play essential and redundant roles upstream of TE fate decisions during preimplantation development in cattle.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829772","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}

{"title":"S100A11 promotes lipid metabolism and activates the apoptosis in polycystic ovary syndrome.","authors":"Xiao Yang, Qi Jiang, Yanbo Du, Lei Yan, Hong Lv, Muzi Li, Zihan Xu","doi":"10.1530/REP-24-0232","DOIUrl":"https://doi.org/10.1530/REP-24-0232","url":null,"abstract":"<p><p>Apoptosis of ovarian granulosa cells (GCs) affects the development and maturation of oocyte in Polycystic ovary syndrome (PCOS).The objective of our study was to examine the impact of S100A11 on granulosa cells in individuals with polycystic ovary syndrome. We found that the S100A11 level was higher in the ovarian granulosa cells of PCOS patients and ovarian tissue of PCOS mouse models. S100A11 overexpression experiments demonstrated a decrease in the cell proliferation, upregulating the apoptosis and blocking the cell cycle. Immunofluorescence staining showed that S100A11 proteins were mainly located in the nucleus. Integrating the RNA-seq and ChIP-seq, this study found that S100A11 mainly regulated the genetic transcription and lipid metabolism. Furthermore, lipid accumulation and oxidative stress increasing were detected in the S100A11 overexpression group. We also revealed that S100A11 upregulated the p-DRP1 Ser616 to induce the mitochondrial fission.In conclusion, S100A11 upregulated the phospho-DRP1 to activate ovarian granulosa cell apoptosis and induced the lipid metabolism and oxidative stress to regulate the follicular reserve in PCOS. The findings present a novel therapeutic concept for polycystic ovary syndrome.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829687","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}