{"title":"RNA splicing and alternative polyadenylation profile during sheep zygotic genome activation†.","authors":"Mingtian Deng, Hua Yang, Ying Chen, Nasser Ghanem, Yingnan Yang, Xiaowei Chen, Jinhao Zhang, Feng Wang, Liqin Wang, Yanli Zhang","doi":"10.1093/biolre/ioaf068","DOIUrl":"10.1093/biolre/ioaf068","url":null,"abstract":"<p><p>Zygotic genome activation (ZGA) is a critical biological step in mammalian early embryo development. However, ZGA initiation in sheep and the related sophisticated RNA metabolism remains largely unknown. Here, we observed extensive alterations in gene expression and DNA methylation patterns, along with elevated levels of RNA polymerase II (RNAPII) and its phosphorylation at serine 2 (RNAPII-Ser2P) at the 16-cell stage. Moreover, the embryos were blocked at the 16-cell stage embryo when treated with α-Amanitin, indicating that ZGA is initiated at the 16-cell stage in sheep in vitro fertilized embryos. To uncover the sophisticated RNA metabolism during ZGA, we conducted weighted gene co-expression network analysis and identified 1957 critical maternal genes, including TET3, UHRF1, and KIF2C. Using dapars analysis, we discovered 1058 and 933 lengthened alternative polyadenylation (APA) events during ZGA in sheep and mice. Specifically, genes exhibiting shorten APA were highly expressed at sheep 16-cell stage embryos and mouse 2-cell stage embryos. During ZGA in sheep and mice, 2675 and 1963 genes showed exon skipping, an alternative splicing (AS) events, which is related to RNA binding, translation, gamete generation, and reproduction. Of note, inhibition of AS led to 2-cell block in mice and 8/16-cell block in sheep. Moreover, 5-EU, RNAPII, and RNAPII-Ser2P signal were decreased in AS inhibited 2-cell embryos in mice, suggesting AS might regulate the ZGA process by crosstalk with RNAPII. In conclusion, our data confirmed ZGA initiation at the 16-cell stage embryos, and provides insights into the complex RNA metabolism during ZGA in mammals.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1086-1099"},"PeriodicalIF":3.1,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742025","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}
Thomas Behrens, Janaki Balasubramanian, Marilin Ivask, Monika Nõmm, Ants Kavak, Jan Bojsen-Møller Secher, Haja N Kadarmideen, Maria Belen Rabaglino
{"title":"In vitro processes alter the embryonic disc epigenome and transcriptome in the pre-implantation elongated bovine embryo†.","authors":"Thomas Behrens, Janaki Balasubramanian, Marilin Ivask, Monika Nõmm, Ants Kavak, Jan Bojsen-Møller Secher, Haja N Kadarmideen, Maria Belen Rabaglino","doi":"10.1093/biolre/ioaf095","DOIUrl":"https://doi.org/10.1093/biolre/ioaf095","url":null,"abstract":"<p><p>The objective was to quantify the effect of the in vitro procedures on the epigenome and transcriptome of the embryonic disc (ED) and extra-embryonic membranes (EEM) of day 15 in vitro produced (IVP) conceptuses compared to in vivo (IVV) counterparts. IVP embryos (n = 7) were cultured serum-free until transfer at day 7. IVV embryos (n = 9) were conceived by artificial insemination. Animals were flushed at day 15 of gestation, and sections of ED and EEM were subjected to DNA and mRNA extraction for whole genome bisulfite or RNA sequencing. Raw fastq files were aligned to the ARS-UCD1.3 bovine genome. Processed data were integrated through a multi-omics approach based on machine learning to determine the key ontological terms characterizing each embryonic tissue lineage according to their methylome and transcriptome, followed by overrepresentation analyses (adjusted p-value<0.05) of differentially methylated genes (DMG), differentially expressed genes (DEG) or genes both differentially methylated and differentially expressed in the ED or EEM of IVP compared to IVV conceptuses. Results demonstrated that identified critical ontological terms for the ED (such as somitogenesis, mesoderm formation, gastrulation) and the BMP and Wnt signaling pathways were enriched among hypermethylated DMG, down-regulated DEG, and genes hypermethylated in the promoter and inhibited in expression, in the ED of IVP embryos. Genes hypermethylated in the promoter and inhibited in expression in the EEM of IVP conceptuses were involved in epigenetic regulation. In conclusion, the in vitro process alters the development of main linage tissues in the pre-implantation embryo, even after interaction with the maternal environment.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282252","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}
Tsuyoshi Murata, Kevin K Prifti, Xiaofeng Ma, Lindsey N Kent, Antonina I Frolova, Sarah K England
{"title":"Myometrial smooth muscle Katp channel activity is attenuated in a mouse model of diet-induced obesity during pregnancy.","authors":"Tsuyoshi Murata, Kevin K Prifti, Xiaofeng Ma, Lindsey N Kent, Antonina I Frolova, Sarah K England","doi":"10.1093/biolre/ioaf130","DOIUrl":"https://doi.org/10.1093/biolre/ioaf130","url":null,"abstract":"<p><p>Labor dystocia occurs in 21% of deliveries, increasing the risk of adverse maternal and neonatal outcomes. Pregnant women with obesity have an increased prevalence of labor dystocia due to reduced myometrial contractility. Similarly, in a mouse model, diet-induced obesity (DIO) led to reduced uterine contractility and dystocia, although the underlying mechanisms are not fully understood. Here, we focused on the KATP channel, which links metabolic changes to cellular excitability. KATP channels are activated by a decrease in intracellular adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio, resulting in cell membrane hyperpolarization and cytoprotection. We show that myometrial smooth muscle cells (MSMCs) isolated from DIO mice had lower mean KATP currents than MSMCs from control-diet (CON) mice. KATP channel blockade by glibenclamide significantly reduced the ex vivo frequency of contractility in uterine tissue from CON mice but not in tissue from DIO mice, suggesting reduced KATP channel activity in DIO mice. Expression of the KATP subunits Kir6.1 and Sur2 was similar between uterine tissues from CON and DIO mice. Analysis of metabolomics data revealed that uterine tissue from DIO mice had a higher ATP/ADP ratio and lower quantities of several phosphatidylinositols than tissue from CON mice. Finally, MSMCs from DIO mice had fewer caveolae and less colocalization of Kir6.1 and caveolin 1 than MSMCs from CON mice. Our results suggest that reduced myometrial KATP channel activity contributes to dampened uterine contractility in obese pregnant mice.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282253","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":"RAB3IL1: A Key Regulator in the Autophagy-Ferroptosis Axis of Male Infertility.","authors":"Binyu Ma, Zhidan Hong, Ying Gao, Yingjing Wan, Xuanyi He, Mei Wang, Yuanzhen Zhang","doi":"10.1093/biolre/ioaf127","DOIUrl":"https://doi.org/10.1093/biolre/ioaf127","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death characterized by phospholipid peroxidation, plays a pivotal role in various diseases. However, its involvement in male infertility, particularly in idiopathic non-obstructive azoospermia (iNOA), remains largely unexplored. iNOA accounts for 10-15% of male infertility cases, presenting a significant clinical challenge due to its unknown origins. This study investigated the potential link between ferroptosis and iNOA, revealing excessive activation of both ferroptosis and autophagy in the testes of iNOA patients, along with severe disruption of the blood-testis barrier (BTB). The BTB, formed by tight junctions between Sertoli cells, is essential for maintaining the spermatogenesis microenvironment. Using the ferroptosis inducer erastin, an antagonist of the cystine antiporter SLC7A11, we established a ferroptosis model in mouse Sertoli cells, demonstrating that ferroptosis activation led to cytoskeletal disarray and BTB disruption, accompanied by excessive autophagy activation. Notably, inhibition of autophagy using 3-methyladenine significantly rescued erastin-induced ferroptosis and restored BTB integrity, highlighting a crucial cross-talk between ferroptosis and autophagy in maintaining the spermatogenic microenvironment. Furthermore, through combined transcriptome analysis of iNOA testes and Sertoli cells, we identified RAB3IL1 as a novel regulator of ferroptosis. Mechanistically, Rab3il1 knockdown induced ferroptosis via translocation of SLC7A11, resulting in cytoskeletal defects and BTB damage. Our findings underscore the critical role of the ferroptosis-autophagy axis, regulated by RAB3IL1, in preserving the spermatogenic microenvironment, offering a potential therapeutic target for restoring spermatogenesis in iNOA patients.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274184","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}
Na Zhang, Yan You, Yanhua Zhao, Ying Lian, Xiulian Ren, Zhongwei Wang, Yapeng Wang, JianGen Xu, Lei Lei, Jianfei Dong, Ping Liu
{"title":"Near infrared LED Irradiation Reverses the Declining Quality of Mice Post-Ovulatory Aging and Reproductive Aged Oocytes.","authors":"Na Zhang, Yan You, Yanhua Zhao, Ying Lian, Xiulian Ren, Zhongwei Wang, Yapeng Wang, JianGen Xu, Lei Lei, Jianfei Dong, Ping Liu","doi":"10.1093/biolre/ioaf129","DOIUrl":"https://doi.org/10.1093/biolre/ioaf129","url":null,"abstract":"<p><p>The advanced maternal age is strongly correlated with a notable decline in oocyte quality, yet definitive and effective strategies to enhance it remain incompletely identified. In this study, we reported that near-infrared light, administered in vitro, efficaciously improves the quality of post-ovulatory aging (POA) and reproductive aged oocytes by recovering mitochondrial activity. Near-infrared light has the capacity to ameliorate abnormalities in mitochondrial membrane potential, optimize mitochondrial distribution, augment ATP synthesis, and modulate the expression of mitochondrial-related genes. It can consequently enhance the quality of oocytes by reducing the reactive oxygen species (ROS) level, improving the abnormal distribution of spindles and maintaining the fertilization ability. Moreover, transcriptome analysis also shows that the beneficial effect of near-infrared light on POA and reproductive aged oocytes is mediated by restoration of mitochondrial function. Collectively, our data reveal that the near-infrared light treatment, especially of 810 nm or 950 nm with a cumulative dosage of 1.5 J*cm-2, is a feasible approach to protect oocytes from POA and reproductive aged deterioration, contributing to the improvement of reproductive outcomes of aged women and assisted reproductive technology.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274183","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":"Programmed DNA elimination occurs during early gametogenesis in hybridogenetic hybrids from Hexagrammos genus.","authors":"Dmitrij Dedukh, Kenta Nitsu, Takafumi Fujimoto, Shota Suzuki, Hiroyuki Munehara","doi":"10.1093/biolre/ioaf125","DOIUrl":"https://doi.org/10.1093/biolre/ioaf125","url":null,"abstract":"<p><p>Hybridogenesis is a unique type of reproduction found in hybrids, producing offspring that are partial (hemiclonal) genetic replicas of one parent. Along the southern coast of Hokkaido, Japan, two types of interspecies hybrids have been identified among three Hexagrammos species: Hexagrammos octogrammus (Hoc), H. otakii (Hot), and Hexagrammos agrammus (Hag). These hybrids are characterized by fertile females reproducing via hybridogenesis. During oogenesis of hybrids, the paternal haploid genome (Hag or Hot) is excluded, while only the maternal genome (Hoc) retains and transmits to gametes. This study investigates the mechanism of genome elimination in Hexagrammos hybrids through a comparative analysis of gonadal development in one-year-old juveniles and adult individuals of hybrids and their parental species. Comparative genomic hybridization on whole-mount gonads from Hoc/Hot and (Hoc/Hag) × Hag hybrids revealed gonocytes containing genomes of both parental species and gonocytes with only Hoc genome, suggesting that genome elimination occurs during early gametogenesis. In Hoc but not in Hot or Hag species, we observed heterochromatin foci enriched with H3K9me3 epigenetic histone modification. Similar foci were found in hybrids, confirming the presence of Hoc genome in their gonocytes. Furthermore, we detected micronuclei in the cytoplasm of gonocytes in parental species and hybrids. Although micronuclei were rare, their frequency was significantly higher in hybrids compared to parental species. Within micronuclei in Hoc/Hot and (Hoc/Hag) × Hag hybrids, we identified Hot and Hag chromosomes or their fragments, respectively. Thus, in Hexagrammos hybrids, genome elimination likely occurs during early gametogenic stages and is accompanied by micronuclei formation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233077","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":"Decoding the Maternal-Fetal Dialogue: NK Cell Education in Reproductive Outcomes†.","authors":"Zhuoxu He, Dong Liu, Yueli Mu, Hong Li","doi":"10.1093/biolre/ioaf124","DOIUrl":"https://doi.org/10.1093/biolre/ioaf124","url":null,"abstract":"<p><p>Natural killer (NK) cell education, a dynamic and finely tuned process, is essential for calibrating decidual NK (dNK) cell responsiveness at the maternal-fetal interface. This education process, governed by distinct receptor-ligand interactions, refines dNK cell function to maintain immune tolerance while preserving responsiveness to pathological threats. Killer-cell immunoglobulin-like receptors (KIRs) interacting with human leukocyte antigen (HLA)-C dictate a balance between activation and inhibition, shaping dNK cell adaptability to maternal-fetal genetic variation. The NKG2A-HLA-E axis establishes a foundational inhibitory checkpoint, ensuring immune tolerance through metabolic and functional programming. LILRB1-HLA-G interactions promote immunomodulatory and angiogenic functions crucial for placental development, while SLAM family receptors (SFRs), including 2B4-CD48, modulate activation thresholds and restrain excessive cytotoxicity. Disruptions in these finely orchestrated pathways contribute to recurrent implantation failure, pregnancy loss, and preeclampsia. This review synthesizes the diverse mechanisms of NK cell education, highlighting how specific receptor-ligand interactions regulate dNK cell function and maternal-fetal immune adaptation. A deeper understanding of these pathways not only enhances our comprehension of reproductive immunology but also paves the way for novel therapeutic strategies targeting immune dysregulation in pregnancy-related disorders.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233076","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":"Combined treatment with IGF1, CoQ10 and melatonin improves the quality of bovine oocytes and heat-shocked blastocysts†.","authors":"Hang Zhang, Baigao Yang, Peipei Zhang, Jianhua Cao, Xiaomeng Zhang, Smhaa Gahallah, Zvi Roth, Pengcheng Wan, Xueming Zhao","doi":"10.1093/biolre/ioaf123","DOIUrl":"https://doi.org/10.1093/biolre/ioaf123","url":null,"abstract":"<p><p>Heat stress significantly impairs cattle fertility, particularly affecting oocytes and developing blastocysts. Developing strategies to improve embryonic development under heat stress is crucial for advancing the cattle breeding industry. This study evaluated the effects of a combined treatment with insulin-like growth factor 1 (IGF1), coenzyme Q10 (CoQ10), and melatonin (MT) (i.e., IGF1+CoQ10+MT) on oocyte competence and genes expression in the formed blastocysts. Bovine in vitro fertilization (IVF) blastocysts were assessed under heat shock (41°C for 12 hours) and control conditions (38.5°C). The combined supplementation of IGF1 (100 ng/mL), CoQ10 (50 μM), and MT (1 μM) during in vitro maturation (IVM) and in vitro culture (IVC) improved oocyte quality and competence by reducing reactive oxygen species (ROS) levels and apoptosis, increasing mitochondrial membrane potential (ΔΨm), optimizing mitochondrial distribution, and upregulating quality related genes. Heat shock decreased ATP content, increased apoptosis, and affected gene expression related to development, apoptosis, ubiquitination, and autophagy, impacting blastocyst development. The combined treatment mitigated heat shock damage by enhancing ATP content, reducing apoptosis, and improving gene expression, thus improving blastocyst quality.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224125","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}
Zijing Zhang, Lu Huang, Lynae Brayboy, Michael Birrer
{"title":"Single-cell analysis of ovarian myeloid cells identifies age associated changes in macrophages and signaling dynamics.","authors":"Zijing Zhang, Lu Huang, Lynae Brayboy, Michael Birrer","doi":"10.1093/biolre/ioaf122","DOIUrl":"10.1093/biolre/ioaf122","url":null,"abstract":"<p><p>The aging of mammalian ovary is accompanied by an increase in tissue fibrosis and heightened inflammation. Myeloid cells, including macrophages, monocytes, dendritic cells, and neutrophils, play pivotal roles in shaping the ovarian tissue microenvironment and regulating inflammatory responses. However, a comprehensive understanding of the roles of these cells in the ovarian aging process is lacking. To bridge this knowledge gap, we utilized single-cell RNA sequencing (scRNAseq) and flow cytometry analysis to functionally characterize CD45+ CD11b+ myeloid cell populations in young (3 months old) and aged (14-17 months old) murine ovaries. Our dataset unveiled the presence of five ovarian macrophage subsets, including a Cx3cr1lowCd81hi subset unique to the aged murine ovary. Most notably, our data revealed significant alterations in ANNEXIN and TGFβ signaling within aged ovarian myeloid cells, which suggest a novel mechanism contributing to the onset and progression of aging-associated inflammation and fibrosis in the ovarian tissue.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207565","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 Single and Combined Effects of Decabromodiphenyl Ethane and Mixed Microplastics on Male Mice Reproductive Toxicity.","authors":"Zhipeng Qi, Wei Li, Linwei Pan, Weiyi Song, Yu Deng, Jing Li, Lichun Xu, Jikuan Yan, Cheng Zou, Haibo Yang, Xinxin Yang","doi":"10.1093/biolre/ioaf121","DOIUrl":"https://doi.org/10.1093/biolre/ioaf121","url":null,"abstract":"<p><p>The expansive surface area of microplastics (MPs) allow them to retain pollutants, however, the combined toxicity of mixed MPs and organic contaminants remains poorly studied. The semen quality of men worldwide was observed to exhibit downward trends. This study investigates the reproductive toxicity and underlying mechanisms of male mice exposed to MPs and novel brominated flame retardants decabromodiphenyl ethane (DBDPE), individually or combined. Male mice were treated by oral gavage with corn oil, 5 or 50 mg/kg DBDPE, 10 mg/kg MPs (a mixture of PE (Polyethylene) and PVC (Polyvinyl chloride)), and DBDPE+MPs (50 mg/kg DBDPE mixed with 10 mg/kg MPs) for 7 weeks. Our results suggested DBDPE alone decreased the sex hormones levels and sperm count, whereas MPs alone had no significant effect. DBDPE and/or MPs impaired testicular morphology, sperm malformation rate, oxidative stress levels, and apoptosis. Our results of transcriptomics from GC-2 cells indicated that DBDPE and MPs lead to changes in oxidative stress, apoptosis, inflammation, proliferation and differentiation. Furthermore, DBDPE and/or MPs exposure inhibited the Kelch-like ECH-associated protein 1- NF-E2-related factor 2 (Keap1-Nrf2) signaling pathway. Moreover, the combined treatment of MPs and DBDPE exerted an antagonistic effect on the reproductive system of mice. This study provides valuable insights into the mechanisms of joint action in reproductive toxicity in mammals due to the combined exposure to MPs and DBDPE.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191439","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}