ReproductionPub Date : 2024-08-05Print Date: 2024-09-01DOI: 10.1530/REP-23-0336
Wenqian Xiong, Jie Jin, Yi Liu
{"title":"METTL3-dependent m6A modification facilitates decreased endometrial decidualization via attenuation of MET in endometriosis.","authors":"Wenqian Xiong, Jie Jin, Yi Liu","doi":"10.1530/REP-23-0336","DOIUrl":"10.1530/REP-23-0336","url":null,"abstract":"<p><strong>In brief: </strong>Failure to induce mesenchymal-epithelial transition (MET) during stromal cell decidualization can lead to consequences such as impaired fertility in patients with endometriosis. METTL3-mediated m6A modification plays an important role in attenuating MET and defective decidualization of endometrial stromal cells and contributes to the development of reduced endometrial receptivity in endometriosis.</p><p><strong>Abstract: </strong>Mesenchymal-epithelial transition (MET)-mediated endometrial decidualization is pivotal for achieving endometrial receptivity and successful pregnancy. We observed blockade of MET in the eutopic secretory endometrium of patients with endometriosis, but the underlying mechanism is unknown. In this study, real-time PCR was used to detect PRL and IGFBP1 expression, whereas western blotting was used to detect the expression of MET markers and METTL3. Phalloidin staining was used to identify changes in cell morphology. M6A levels were quantified using a colorimetric method and m6A dot blots, and functional analysis was performed using spheroid adhesion assays. We first found that increased E-cadherin expression was accompanied by decreased vimentin and Slug expression in the eutopic secretory endometrium of individuals with endometriosis. We also detected a significant increase in both the m6A level and the expression of the related methyltransferase METTL3. Finally, METTL3 expression was negatively correlated with PRL, IGFBP1, and MET markers expression. Collectively, our findings suggest that METTL3 mediates m6A modification, thereby inhibiting MET formation within the eutopic secretory endometrium of patients with endometriosis. Increased METTL3-mediated m6A modification plays a crucial role in attenuating MET formation and decidualization impairment in endometrial stromal cells, ultimately contributing to compromised endometrial receptivity in individuals with endometriosis. These insights could lead to the identification of potential therapeutic targets for improving both endometrial receptivity and pregnancy rate among individuals affected by endometriosis.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088413","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}
ReproductionPub Date : 2024-08-02Print Date: 2024-09-01DOI: 10.1530/REP-24-0171
Laura Woods, Wendy Dean, Myriam Hemberger
{"title":"REPRODUCTIVE AGEING: Altered histone modification landscapes underpin defects in uterine stromal cell decidualization in aging females.","authors":"Laura Woods, Wendy Dean, Myriam Hemberger","doi":"10.1530/REP-24-0171","DOIUrl":"10.1530/REP-24-0171","url":null,"abstract":"<p><strong>In brief: </strong>Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females.</p><p><strong>Abstract: </strong>Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated 'ground' state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141601423","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}
ReproductionPub Date : 2024-08-02Print Date: 2024-09-01DOI: 10.1530/REP-24-0004
Eva Held-Hoelker, Jessica Kurzella, Dessie Salilew-Wondim, Franca Rings, Dawit Tesfaye, Ernst Tholen, Christine Grosse-Brinkhaus, Michael Hoelker
{"title":"L-Carnitine sustainably affects bioenergetic profile of bovine blastocysts and transcriptome profile of elongation-stage embryos.","authors":"Eva Held-Hoelker, Jessica Kurzella, Dessie Salilew-Wondim, Franca Rings, Dawit Tesfaye, Ernst Tholen, Christine Grosse-Brinkhaus, Michael Hoelker","doi":"10.1530/REP-24-0004","DOIUrl":"10.1530/REP-24-0004","url":null,"abstract":"<p><strong>In brief: </strong>In the present study the sustainable effect of L-carnitine during the culture period on the post-transfer development was investigated. Taken together, we uncovered direct effects of L-carnitine on the bioenergetic profile of day 7 blastocysts along with sustainable effects on mtDNA copy numbers and transcriptome profile of bovine day 14 embryos.</p><p><strong>Abstract: </strong>L-Carnitine (LC) is known to play key roles in lipid metabolism and antioxidative activity, implicating enhanced cryotolerance of bovine blastocysts. However, sustainability of LC supplementation during culture period on preimplantation development beyond the blastocyst stage has not been investigated so far. Therefore, all embryos were cultured under fatty acid-free conditions, one group with LC (LC embryos) and the control group without LC (control) supplementation. Transfer to recipients was conducted on day 6. Elongation-stage embryos were recovered on day 14; metrics of embryo recollection, developmental rates as regards early elongation-stage as well as mean embryo length did not differ between the groups. Gene expression analyses via NGS revealed 341 genes to be differentially regulated between elongation-stage embryos derived from LC supplementation compared to controls. These played mainly a role in molecular functions and biological processes like oxidoreductase activity, ATP-dependent activity, cellular stress, and respiration. Pathways like oxidative phosphorylation and thermogenesis, extracellular matrix receptor signaling, PI3K-Akt, and focal adhesion were affected by differentially regulated genes. Moreover, all DEGs located on the mitochondria were significantly downregulated in LC embryos, being in line with lower mitochondrial copy number and mtDNA integrity compared to the control group. Finally, we uncovered alterations of the bioenergetic profile on day 7 as a consequence of LC supplementation for the first time, revealing significantly higher oxygen consumption rates, ATP linked respiration and spare capacity for LC embryos. In summary, we uncovered direct effects of LC supplementation during the culture period on the bioenergetic profile along with sustainable effects on mtDNA copy numbers and transcriptome profile of bovine day 14 embryos.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451401","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}
ReproductionPub Date : 2024-08-02Print Date: 2024-09-01DOI: 10.1530/REP-24-0128
Min Zhang, Jia-Shun Wu, Xiao Han, Rui-Jie Ma, Jia-Li Xu, Ming-Tao Xu, Hong-Jie Yuan, Ming-Jiu Luo, Jing-He Tan
{"title":"Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes.","authors":"Min Zhang, Jia-Shun Wu, Xiao Han, Rui-Jie Ma, Jia-Li Xu, Ming-Tao Xu, Hong-Jie Yuan, Ming-Jiu Luo, Jing-He Tan","doi":"10.1530/REP-24-0128","DOIUrl":"10.1530/REP-24-0128","url":null,"abstract":"<p><strong>In brief: </strong>Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos.</p><p><strong>Abstract: </strong>Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470450","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}
ReproductionPub Date : 2024-07-29Print Date: 2024-09-01DOI: 10.1530/REP-23-0480
Wen Zheng, Liang Zhang, Kailai Cai, Kongju Wu, Ge Liang, Lu Zhang, Lihui Liao, Fujun Shen, Wenping Zhang, Li Wang, Yan Li, Ye Wang, Jie Kou, Yi Zhong, Xin Li, Jingqiu Cheng, Meng Gong, Rong Hou
{"title":"Gestational giant panda plasma metabolomics: amino acid metabolism characteristics may predict panda pregnancy outcomes.","authors":"Wen Zheng, Liang Zhang, Kailai Cai, Kongju Wu, Ge Liang, Lu Zhang, Lihui Liao, Fujun Shen, Wenping Zhang, Li Wang, Yan Li, Ye Wang, Jie Kou, Yi Zhong, Xin Li, Jingqiu Cheng, Meng Gong, Rong Hou","doi":"10.1530/REP-23-0480","DOIUrl":"10.1530/REP-23-0480","url":null,"abstract":"<p><strong>In brief: </strong>The metabolic processes of the gestation period in pandas remain poorly understood. Our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.</p><p><strong>Abstract: </strong>There has been remarkable progress in the conservation and reproduction of giant pandas. However, the physiology of the gestation period in pandas remains poorly understood. The metabolic processes from estrus to pregnancy are dynamic and precisely regulated, playing a crucial role in pregnancy and related dysfunctions. In this study, we conducted a metabolomic analysis of 37 blood samples collected from pandas in estrus, acyclic, and potential pregnant states, employing rigorous screening to minimize the influence of diet. Our findings suggest that a reduced appetite can serve as an indicator for evaluating implantation time, representing a characteristic response to pregnancy and aiding in the prediction of delivery time in pregnant pandas. Metabolomic results indicate great metabolism variation from estrus to pregnancy, highlighting the association between amino acid metabolism and pregnancy outcomes. Compared to other pandas, individuals who successfully bred exhibit significantly elevated levels of arginine and histidine, even 2 months before experiencing a reduced appetite. Furthermore, the lipid profile undergoes distinct dynamic changes only in estrus samples. In summary, our study comprehensively characterizes the metabolism of giant pandas during gestation and proposes arginine and histidine as potential novel biomarkers for detecting the pregnancy state of giant pandas.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470451","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}
ReproductionPub Date : 2024-07-13Print Date: 2024-08-01DOI: 10.1530/REP-23-0496
Wenjie Dai, Hong Yang, Bo Xu, Tiantian He, Ling Liu, Zhen Zhang, Liyang Ding, Xiuying Pei, Xufeng Fu
{"title":"3D hUC-MSC spheroids exhibit superior resistance to autophagy and apoptosis of granulosa cells in POF rat model.","authors":"Wenjie Dai, Hong Yang, Bo Xu, Tiantian He, Ling Liu, Zhen Zhang, Liyang Ding, Xiuying Pei, Xufeng Fu","doi":"10.1530/REP-23-0496","DOIUrl":"10.1530/REP-23-0496","url":null,"abstract":"<p><strong>In brief: </strong>This study reveals that orthotopic transplantation of 3D hUC-MSC spheroids is more effective than monolayer-cultured hUC-MSCs in improving POF and distinctly reducing oxidative stress through the paracrine effect, thereby preventing apoptosis and autophagy of GCs.</p><p><strong>Abstract: </strong>Premature ovarian failure (POF) is a common reproductive disease in women younger than 40 years old, and studies have demonstrated that the application of human umbilical cord mesenchymal stem cells (hUC-MSCs) is a promising therapy strategy for POF. Given the previously established therapeutic advantages of 3D MSC spheroids, and to evaluate their effectiveness, both 3D hUC-MSC spheroids and monolayer-cultured hUC-MSCs were employed to treat a cyclophosphamide-induced POF rat model through orthotopic transplantation. The effects of these two forms on POF were subsequently assessed by examining apoptosis, autophagy, and oxidative damage in ovarian granulosa cells (GCs). The results indicated that hUC-MSC spheroids exhibited superior treatment effects on resisting autophagy, apoptosis, and oxidative damage in GCs compared to monolayer-cultured hUC-MSCs. To further elucidate the impact of hUC-MSC spheroids in vitro, a H2O2-induced KGN cells model was established and co-cultured with both forms of hUC-MSCs. As expected, the hUC-MSC spheroids also exhibited superior effects in resisting apoptosis and autophagy caused by oxidative damage. Therefore, this study demonstrates that 3D hUC-MSC spheroids have potential advantages in POF therapy; however, the detailed mechanisms need to be further investigated. Furthermore, this study will provide a reference for the clinical treatment strategy of POF.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443217","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}
ReproductionPub Date : 2024-07-13Print Date: 2024-08-01DOI: 10.1530/REP-24-0069
Martina Jabloñski, Florenza A La Spina, Liza J Schiavi-Ehrenhaus, Clara I Marín-Briggiler, Matias D Gomez-Elias, Dario Krapf, Pablo E Visconti, Diego Krapf, Guillermina M Luque, Mariano G Buffone
{"title":"Dual role of valosin-containing protein (VCP/p97) in mouse sperm during capacitation.","authors":"Martina Jabloñski, Florenza A La Spina, Liza J Schiavi-Ehrenhaus, Clara I Marín-Briggiler, Matias D Gomez-Elias, Dario Krapf, Pablo E Visconti, Diego Krapf, Guillermina M Luque, Mariano G Buffone","doi":"10.1530/REP-24-0069","DOIUrl":"10.1530/REP-24-0069","url":null,"abstract":"<p><p>Valosin-containing protein (VCP; aka p97), a member of the AAA (ATPases Associated with various cellular Activities) family, has been associated with a wide range of cellular functions. While previous evidence has shown its presence in mammalian sperm, our study unveils its function in mouse sperm. Notably, we found that mouse VCP does not undergo tyrosine phosphorylation during capacitation and exhibits distinct localization patterns. In the sperm head, it resides within the equatorial segment and, following acrosomal exocytosis, it is released and cleaved. In the flagellum, VCP is observed in the principal and midpiece. Furthermore, our research highlights a unique role for VCP in the cAMP/PKA pathway during capacitation. Pharmacological inhibition of sperm VCP led to reduced intracellular cAMP levels that resulted in decreased phosphorylation in PKA substrates and tyrosine residues and diminished fertilization competence. Our results show that in mouse sperm, VCP plays a pivotal role in regulating cAMP production, probably by the modulation of soluble adenylyl cyclase activity.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443218","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}
ReproductionPub Date : 2024-07-02Print Date: 2024-08-01DOI: 10.1530/REP-24-0022
Gen L Takei, Yasuhiro Horibata, Fubito Toyama, Keitaro Hayashi, Asuka Morita, Motoshi Ouchi, Tomoe Fujita
{"title":"Hamster spermatozoa incorporate hypotaurine via TauT for self-protection.","authors":"Gen L Takei, Yasuhiro Horibata, Fubito Toyama, Keitaro Hayashi, Asuka Morita, Motoshi Ouchi, Tomoe Fujita","doi":"10.1530/REP-24-0022","DOIUrl":"10.1530/REP-24-0022","url":null,"abstract":"<p><strong>In brief: </strong>Mammalian spermatozoa actively generate reactive oxygen species (ROS) during capacitation, a maturational process necessary for fertilization in vivo. This study shows that hypotaurine, a precursor of taurine present in the oviduct, is incorporated and concentrated in hamster sperm cells via the taurine transporter, TauT, for cytoprotection against self-produced ROS.</p><p><strong>Abstract: </strong>To achieve fertilization competence, mammalian spermatozoa undergo capacitation, during which they actively generate reactive oxygen species (ROS). Therefore, mammalian spermatozoa must protect themselves from these self-generated ROS. The mammalian oviductal fluid is rich in hypotaurine, a taurine precursor, which reportedly protects mammalian spermatozoa, including those of hamsters, from ROS; however, its precise mechanism remains unknown. This study aimed to elucidate the mechanism underlying hypotaurine-mediated protection of spermatozoa from ROS using hamsters, particularly focusing on the taurine/hypotaurine transporter TauT. The effect of hypotaurine on sperm motility and ROS levels was tested using sperm motility analysis and the CellROX dye and luminol assays. RNA sequencing analysis was performed to verify TauT expression. We found that hypotaurine was necessary for maintaining sperm motility and hyperactivated motility. Hypotaurine did not scavenge extracellular ROS but lowered intracellular ROS levels and was incorporated and concentrated in hamster spermatozoa. TauT was detected at both mRNA and protein levels. β-Alanine blocked hypotaurine transport, increased intracellular ROS levels, and inhibited hyperactivation. Elimination of Na+ or Cl- ions inhibited hypotaurine transport and increased intracellular ROS levels. Thus, these results indicated that hamster spermatozoa incorporated and concentrated hypotaurine in sperm cells via TauT to protect themselves from self-generated ROS.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141297796","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}
ReproductionPub Date : 2024-07-02Print Date: 2024-08-01DOI: 10.1530/REP-24-0119
Michelle Bellingham, Neil Evans
{"title":"IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Biosolids and male reproduction.","authors":"Michelle Bellingham, Neil Evans","doi":"10.1530/REP-24-0119","DOIUrl":"10.1530/REP-24-0119","url":null,"abstract":"<p><p>Over the past 50 years, there has been a concerning decline in male reproductive health and an increase in male infertility which is now recognised as a major health concern globally. While male infertility can be linked to some genetic and lifestyle factors, these do not fully explain the rate of declining male reproductive health. Increasing evidence from human and animal studies suggests that exposure to chemicals found ubiquitously in the environment may in part play a role. Many studies on chemical exposure, however, have assessed the effects of exposure to individual environmental chemicals (ECs), usually at levels not relevant to everyday human exposure. There is a need for study models which reflect the 'real-life' nature of EC exposure. One such model is the biosolids-treated pasture (BTP) sheep model which utilises biosolids application to agricultural land to examine the effects of exposure to low-level mixtures of chemicals. Biosolids are the by-product of the treatment of wastewater from industrial and domestic sources and so their composition is reflective of the ECs to which humans are exposed. Over the last 20 years, the BTP sheep model has published multiple effects on offspring physiology including consistent effects on the male reproductive system in fetal, neonatal, juvenile, and adult offspring. This review focuses on the evidence from these studies which strongly suggests that low-level EC exposure during gestation can alter several components of the male reproductive system and highlights the BTP model as a more relevant model to study real-life EC exposure effects.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284626","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}
ReproductionPub Date : 2024-07-02Print Date: 2024-08-01DOI: 10.1530/REP-24-0018
Xiaoyang Wen, Jingyang Zhang, Zihan Xu, Muzi Li, Xiaotong Dong, Yanbo Du, Zhen Xu, Lei Yan
{"title":"Highly expressed lncRNA H19 in endometriosis promotes aerobic glycolysis and histone lactylation.","authors":"Xiaoyang Wen, Jingyang Zhang, Zihan Xu, Muzi Li, Xiaotong Dong, Yanbo Du, Zhen Xu, Lei Yan","doi":"10.1530/REP-24-0018","DOIUrl":"10.1530/REP-24-0018","url":null,"abstract":"<p><strong>In brief: </strong>Abnormal glucose metabolism may be involved in the pathogenesis of endometriosis. The present study identifies that highly expressed H19 leads to increased aerobic glycolysis and histone lactylation levels in endometriosis.</p><p><strong>Abstract: </strong>Previous studies from our group and others have shown increased IncRNA H19 expression in both the eutopic endometrium and the ectopic endometriosis tissue during endometriosis. In this study, we use immunofluorescence, immunohistochemistry, and protein quantification to determine that levels of aerobic glycolysis and histone lactylation are increased in endometriosis tissues. In human endometrial stromal cells, we found that high H19 expression resulted in abnormal glucose metabolism by examining the levels of glucose, lactate, and ATP and measuring protein levels of enzymes that participate in glycolysis. At the same time, immunofluorescence and western blotting demonstrated increased histone lactylation in H19 overexpressing cells. Altering aerobic glycolysis and histone lactylation levels through the addition of sodium lactate and 2-deoxy-d-glucose demonstrated that increased aerobic glycolysis and histone lactylation levels resulted in enhanced cell proliferation and cell migration, contributing to endometriosis. To validate these findings in vivo, we constructed an endometriosis mouse model, demonstrating similar changes in endometriosis tissues in vivo. Both aerobic glycolysis and histone lactylation levels were elevated in endometriotic lesions. Taken together, these data demonstrate elevated expression levels of H19 in endometriosis patients promote abnormal glucose metabolism and elevated histone lactylation levels in vivo, enhancing cell proliferation and migration and promoting the progression of endometriosis. Our study provides a functional link between H19 expression and histone lactylation and glucose metabolism in endometriosis, providing new insights into disease mechanisms that could result in novel therapeutic approaches.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922788","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}