Yuxin Luo, Yun Zhao, Boqi Zhang, Tong Chen, Xue Chen, Caomeihui Shen, Guitian He, Maosheng Cao, Lu Chen, Yueying Wang, Nan Wang, Jinxin Zong, Xu Zhou, Chunjin Li
{"title":"METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells†.","authors":"Yuxin Luo, Yun Zhao, Boqi Zhang, Tong Chen, Xue Chen, Caomeihui Shen, Guitian He, Maosheng Cao, Lu Chen, Yueying Wang, Nan Wang, Jinxin Zong, Xu Zhou, Chunjin Li","doi":"10.1093/biolre/ioae105","DOIUrl":"10.1093/biolre/ioae105","url":null,"abstract":"<p><p>Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers, and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals. Summary Sentence The present study investigated the effect of NGF on testosterone synthesis in porcine theca cells. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465952","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: Sodium oligomannate's amelioration of reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model depends on the gut microbiome.","authors":"","doi":"10.1093/biolre/ioae099","DOIUrl":"10.1093/biolre/ioae099","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426230","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}
Aydin Guzeloglu, Jeanette V Bishop, Hana Van Campen, Michele R Plewes, Carolina L Gonzalez-Berrios, Jessica N Kincade, John S Davis, Thomas R Hansen
{"title":"Interferon-tau infusion into the ovine corpus luteum delays luteolysis†.","authors":"Aydin Guzeloglu, Jeanette V Bishop, Hana Van Campen, Michele R Plewes, Carolina L Gonzalez-Berrios, Jessica N Kincade, John S Davis, Thomas R Hansen","doi":"10.1093/biolre/ioae084","DOIUrl":"10.1093/biolre/ioae084","url":null,"abstract":"<p><p>Conceptus-derived interferon-tau (IFNT) initiates maternal recognition of pregnancy in ewes by paracrine actions on the endometrium and endocrine action on the corpus luteum (CL). To examine the effect of IFNT on the CL without inducing IFN-stimulated genes (ISGs) in the endometrium, recombinant ovine IFNT (roIFNT) or bovine serum albumin was delivered directly into CLs via osmotic pumps at a rate of 10, 50, or 100 ng/h from days 9 to 12 of the estrous cycle. Endometrial and CL samples were collected on day 12. 50 ng/h of roIFNT induced ISG15 in the CL on day 12 without affecting endometrial ISG15 concentrations. In a second experiment, roIFNT (50 ng/h) was infused into the CL from days 10 to 17 of the estrous cycle and serum samples were collected daily. Serum progesterone concentrations were significantly higher from days 15 to 17 in roIFNT-infused ewes compared to controls. Levels of LHCGR, STAR, CYP11A1, HSL, OPA1, and protein kinase A mRNA and proteins were higher in the roIFNT-infused CLs compared to the controls. Levels of ISG15 and MX1 mRNA increased in the CLs of roIFNT-infused ewes but not in the endometrium. Endometrial ESR1 mRNA and protein concentrations were higher in the controls compared to roIFNT-infused ewes. In conclusion, intra-luteal delivery of roIFNT induced ISGs, stabilized steroidogenesis in the CL, and delayed luteolysis without inducing endometrial IFN-stimulated genes. Inhibition of ESR1 in the endometrium of roIFNT-infused ewes was observed suggesting that direct delivery of IFNT to the CL has an additional anti-luteolytic effect on the endometrium.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309900","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}
Arumugam Kumaresan, Pankaj Yadav, Manish Kumar Sinha, Pradeep Nag, Ebenezer Samuel King John Peter, Jay S Mishra, Sathish Kumar
{"title":"Male infertility and perfluoroalkyl and poly-fluoroalkyl substances: evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa†.","authors":"Arumugam Kumaresan, Pankaj Yadav, Manish Kumar Sinha, Pradeep Nag, Ebenezer Samuel King John Peter, Jay S Mishra, Sathish Kumar","doi":"10.1093/biolre/ioae089","DOIUrl":"10.1093/biolre/ioae089","url":null,"abstract":"<p><strong>Background: </strong>Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and potential threats to reproductive health. Epidemiological studies have established an association between PFAS and male infertility, but the underlying mechanisms are unclear.</p><p><strong>Objectives: </strong>Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and representative PFAS, on bull sperm protein phosphorylation and function.</p><p><strong>Methods: </strong>We exposed bull sperm to PFOS at 10 (average population exposure) and 100 μM (high-exposure scenario), and analyzed global proteomic and phosphoproteomic analysis by TMT labeling and Nano LC-MS/MS. We also measured sperm fertility functions by flow cytometry.</p><p><strong>Results: </strong>PFOS at 10-μM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 μM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, four proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm and also decreased sperm motility, viability, calcium, and mitochondrial membrane potential and increased mitochondrial ROS in a dose-dependent manner.</p><p><strong>Conclusions: </strong>This study demonstrates that PFOS exposure negatively affects phosphorylation of proteins vital for bull sperm function and fertilization.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282952","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}
Bart Leemans, Bart M Gadella, Josephine H E A M Marchand, Ann Van Soom, Tom A E Stout
{"title":"Induction of in vivo-like ciliation in confluent monolayers of re-differentiated equine oviduct epithelial cells†.","authors":"Bart Leemans, Bart M Gadella, Josephine H E A M Marchand, Ann Van Soom, Tom A E Stout","doi":"10.1093/biolre/ioae090","DOIUrl":"10.1093/biolre/ioae090","url":null,"abstract":"<p><p>We recently developed re-differentiated equine oviduct epithelial cell (REOEC) monolayers demonstrating various in vivo morphological characteristics, but lacking secondary ciliation. In this study, we evaluated the effects of fetal bovine serum, reproductive steroid hormones, Wnt- and Notch ligands and inhibitors, and different EOEC seeding densities, in both conventional wells and on microporous membranes, on EOEC morphology and, in particular, secondary ciliation. REOEC monolayers were assessed by confocal microscopy after combined staining of nuclei, cilia, and the cytoskeleton. Only Wnt ligands, Notch inhibitors and oviduct explant cell concentration affected EOEC morphology. Undesirable epithelial-mesenchymal transition was observed in REOEC monolayers exposed to Wnt3a containing medium and Wnt ligand CHIR 99021. With respect to secondary ciliation, only the combined effect of oviduct explant cell concentration and Notch inhibition steered REOEC monolayers to in vivo-like ciliation patterns. De-differentiated EOECs, formed 10 days after oviduct explant cell seeding, were reseeded on inserts; only at initial oviduct explant cell concentrations of 1 and 5 × 106 cells per well was the formation of REOEC monolayers with a high rate of diffuse ciliation supported. Within 1 month after air-liquid interface introduction, >40% and >20% of the REOECs showed secondary cilia, respectively. At higher oviduct explant cell seeding densities secondary ciliation was not supported after re-differentiation. Additionally, Notch inhibition helped boost secondary ciliation rates to >60% in REOEC monolayers with diffuse ciliation only. These monolayers demonstrated higher clathrin expression under follicular phase conditions. Overall, the ciliated REOEC monolayers better resemble in vivo oviduct epithelial cells than previous models.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282951","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":"Correction to: Activation of HAND2-FGFR signaling pathway by lncRNA HAND2-AS1 in adenomyosis.","authors":"","doi":"10.1093/biolre/ioae091","DOIUrl":"10.1093/biolre/ioae091","url":null,"abstract":"","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287687","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}
Hao Yu, Xiaotong Li, Jie Zhao, Wei Wang, Quanwei Wei, Dagan Mao
{"title":"NR4A1-mediated regulation of lipid droplets in progesterone synthesis in goat luteal cells†.","authors":"Hao Yu, Xiaotong Li, Jie Zhao, Wei Wang, Quanwei Wei, Dagan Mao","doi":"10.1093/biolre/ioae085","DOIUrl":"10.1093/biolre/ioae085","url":null,"abstract":"<p><p>Nuclear receptor NR4A1 is a key factor in glycolipid metabolism and steroidogenesis, while lipid droplets serve as crucial dynamic organelles for lipid metabolism in luteal cells. To investigate the effects of NR4A1 on lipid droplet metabolism and progesterone (P4) synthesis in goat corpus luteum in vitro, luteal cells from the middle-cyclic corpus luteum were isolated and treated with Cytosporone B (CSNB, an agonist) or siRNA of NR4A1. Results showed that both low (1 μM) and high (50 μM) concentrations of CSNB promoted lipid droplet accumulation, while NR4A1 knockdown reduced lipid droplet content. CSNB increased while siNR4A1 decreased total cholesterol content; however, CSNB and siNR4A1 did not change triglyceride content. CSNB increased the expression of perilipins at mRNA and protein levels, also increased LDLR, SCARB1, SREBFs, and HMGCR mRNA abundance. Treatment with siNR4A1 revealed opposite results of CSNB, except for HMCGR and SREBF2. For steroidogenesis, 1 μM CSNB increased, but 50 μM CSNB inhibited P4 synthesis, NR4A1 knockdown also reduced the P4 level. Further analysis demonstrated that 1 μM CSNB increased the protein levels of StAR, HSD3B, and P-HSL, while 50 μM CSNB decreased StAR, HSD3B, and CYP11A1 protein levels. Moreover, 50 μM CSNB impaired active mitochondria, reduced the BCL2, and increased DRP1, Caspase 3, and cleaved-Caspase 3 protein levels. siNR4A1 consistently downregulated the P-HSL/HSL ratio and the steroidogenic protein levels. In conclusion, NR4A1-mediated lipid droplets are involved in the regulation of progesterone synthesis in goat luteal cells.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465953","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}
Kevin K Prifti, Ronald McCarthy, Xiaofeng Ma, Brian N Finck, Sarah K England, Antonina I Frolova
{"title":"Obese mice have decreased uterine contractility and altered energy metabolism in the uterus at term gestation†.","authors":"Kevin K Prifti, Ronald McCarthy, Xiaofeng Ma, Brian N Finck, Sarah K England, Antonina I Frolova","doi":"10.1093/biolre/ioae086","DOIUrl":"10.1093/biolre/ioae086","url":null,"abstract":"<p><p>Over 35% of reproductive-age women in the USA have obesity, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity and found that these mice had a higher rate of dystocia than control chow-fed mice. Moreover, compared to control chow-fed mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that diet-induced obesity is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. Diet-induced obesity uteri also had an increase in the abundance of long chain-specific beta-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299955","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}
Wenting Ye, Siyu Xia, Tingting Xie, Huiyun Ye, Yi Yang, Yan Sun, Jing Cai, Xiaoqing Luo, Lili Zhou, Yali Song
{"title":"Klotho accelerates the progression of polycystic ovary syndrome through promoting granulosa cell apoptosis and inflammation†.","authors":"Wenting Ye, Siyu Xia, Tingting Xie, Huiyun Ye, Yi Yang, Yan Sun, Jing Cai, Xiaoqing Luo, Lili Zhou, Yali Song","doi":"10.1093/biolre/ioae094","DOIUrl":"10.1093/biolre/ioae094","url":null,"abstract":"<p><p>The morbidity of polycystic ovary syndrome (PCOS) is in highly increasing rate nowadays. PCOS not only affects the fertility in women, but also threatens the health of whole life. Hence, to find the prognostic risk factors is of great value. However, the effective predictors in clinical practice of PCOS are still in blackness. In this study, we found Klotho (KL) was increased in follicular fluid (FF) and primary luteinized granulosa cells (GCs) from PCOS patients with hyperandrogenism. Furthermore, we found follicular KL was negatively correlated with numbers of mature oocytes, and positively correlated with serum testosterone, LH, and LH/FSH levels menstrual cycle and number of total antral follicles in PCOS patients. In primary luteinized GCs, the increased KL was accompanied with upregulation of cell apoptosis and inflammation-related genes. In ovaries of PCOS mice and cultured human KGN cell line, KL was up-regulated and accompanied by apoptosis, inflammation, and mitochondrial dysfunction. Therefore, our findings suggest new mechanisms for granulosa cell injury and revealed to target inhibit KL maybe a new therapeutic strategy for treatment of PCOS.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316655","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":"The potential effect of melatonin on in vitro oocyte maturation and embryo development in animals.","authors":"Parisa Nadri, Azadeh Zahmatkesh, Azizollah Bakhtari","doi":"10.1093/biolre/ioae077","DOIUrl":"10.1093/biolre/ioae077","url":null,"abstract":"<p><p>Melatonin is a hormone mainly secreted by the pineal gland during the circadian cycle, with low levels during the daytime and prominent levels during the night. It is involved in numerous physiological functions including the immune system, circadian rhythm, reproduction, fertilization, and embryo development. In addition, melatonin exerts anti-inflammatory and antioxidant effects inside the body by scavenging reactive oxygen and reactive nitrogen species, increasing antioxidant defenses, and blocking the transcription factors of pro-inflammatory cytokines. Its protective activity has been reported to be effective in various reproductive biotechnological processes, including in vitro maturation (IVM), embryo development, and survival rates. In this comprehensive review, our objective is to summarize and debate the potential mechanism and impact of melatonin on oocyte maturation and embryo development through various developmental routes in different mammalian species.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955946","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}