Molecular Reproduction and Development最新文献

{"title":"Three-Dimensional Magnetic Bioprinting Spheroids as an In Vitro Model to Study the Oviductal Physiology","authors":"Patricia Kubo Fontes,&nbsp;Ana Beatriz Florencio da Silva,&nbsp;Ana Beatriz dos Reis Bartoli,&nbsp;Thays Antunes,&nbsp;Arnaldo Rodrigues dos Santos Júnior,&nbsp;Marcella Pecora Milazzotto","doi":"10.1002/mrd.70049","DOIUrl":"https://doi.org/10.1002/mrd.70049","url":null,"abstract":"<p>In vitro models to study the oviduct are challenged by cellular dedifferentiation, a complex coculture system for embryo production, limited cell lifespan, and/or very complex methodologies. Hence, we aimed to develop an in vitro oviductal model using the magnetic bioprinting system, a three-dimensional (3D) culture system. Using the bovine epithelial and stromal oviductal cells (BOEC and BOSC, respectively), we produced the Oviductal Magnetic Spheroid (OMS), a duo somatic cell spheroid aggregate with self-organization capacity. The OMS showed to be viable for 21 days and recapitulated the oviductal tissue features after 7 days in culture, such as a simple epithelial cell layer facing outwards, expressing ciliation (acetylated tubulin positive) and secretory marker (oviduct-specific glycoprotein 1). Although the responsiveness for hormonal treatment with estradiol and progesterone in an estrous cycle-dependent way might require further improvements, the OMS offers an ethical and practical alternative as a three-dimensional oviductal in vitro model to study oviductal physiology, and maybe, a future platform to test therapies and a technology aiming to improve fertility and assisted reproduction success.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881459","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":"Phospholipase D2 Regulates Microtubule Acetylation by Modulating Gsk3β-Tau Signaling in Mouse Oocytes During Meiotic Maturation","authors":"Ningning Zhang,&nbsp;Ying Tian,&nbsp;Xiangning Xu,&nbsp;Bicheng Wang,&nbsp;Shuo Lou,&nbsp;Jingyi Kang,&nbsp;Jingyu Li,&nbsp;Yuanjing Liang,&nbsp;Jing Weng,&nbsp;Wei Ma","doi":"10.1002/mrd.70051","DOIUrl":"https://doi.org/10.1002/mrd.70051","url":null,"abstract":"<div>\u0000 \u0000 <p>Phospholipase D2 (PLD2) modulates cytoskeletal dynamics and membrane trafficking processes by converting phosphatidylcholine (PC) into phosphatidic acid (PA) and choline within somatic cells. Nonetheless, the role in oocyte meiosis remains largely unknown. Here, we demonstrate that PLD2 is selectively targeted to the meiotic spindle in mouse oocytes. The knockdown of PLD2 via the specific morpholino oligonucleotides (MOs) or its inhibition with VU 0364739 led to a marked increase in α-tubulin acetylation and induced a meiotic arrest at metaphase I (MI), accompanied by misaligned chromosomes. These defects were effectively rescued by the ectopic expression of <i>Pld2</i> complementary RNA (cRNA). Furthermore, our findings implicate the <i>Pld2</i> MO-induced alterations in the AKT-GSK3-Tau signaling cascade in oocytes. The overexpression of a gain-of-function GSK3β mutant (GSK3β^S9A) and a Tau-phosphorylation-enhancing mutant (Tau^P301L) substantially reversed the increased microtubule acetylation and the reduced rate of the first polar body extrusion (PBE) in oocytes lacking PLD2 activity. Additionally, the co-immunoprecipitation revealed a direct physical interaction between PLD2, GSK3β, and Tau in mouse oocytes. Together, PLD2 finely regulates α-tubulin acetylation through the modulation of the AKT-GSK3β-Tau signaling axis, thereby preserving an optimal microtubule dynamic equilibrium and ensuring the fidelity of the spindle apparatus function during oocyte meiosis.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881458","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":"Role of the Ubiquitin-Proteasome System in Mammalian Male Germ Cell Differentiation and Reproductive Fitness","authors":"Héctor Zapata-Carmona,&nbsp;Lina Barón,&nbsp;Milene Kong,&nbsp;Patricio Morales","doi":"10.1002/mrd.70050","DOIUrl":"https://doi.org/10.1002/mrd.70050","url":null,"abstract":"<p>The ubiquitin-proteasome system (UPS) is fundamental for the development and differentiation of male mammalian germ cells. As a key pathway for protein degradation, the UPS maintains cellular homeostasis by removing misfolded, damaged, or excess proteins, thus enabling cells to adapt to physiological and environmental changes. In male reproduction, the UPS regulates critical processes from spermatogenesis to the functionality of mature spermatozoa. During spermatogenesis in seminiferous tubules, the UPS orchestrates cell cycle regulation, apoptosis, and chromatin remodeling, ensuring that only the most viable germ cells differentiate. In the epididymis, the UPS facilitates sperm maturation, granting motility and functional characteristics. In addition, the UPS is essential for sperm capacitation in the female reproductive tract, which is a process critical for fertilization. Dysregulation of the UPS can severely impair male fertility and contribute to infertility and other reproductive disorders. This review provides a detailed examination of the role of the UPS in spermatogenesis, sperm maturation in the epididymis, and capacitation in the female reproductive tract. By exploring the molecular mechanisms underlying these processes, we highlight the clinical implications of UPS dysfunction and offer a comprehensive understanding of its contribution to mammalian reproductive success.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869189","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":"Endometrial Gene Expression Predicts Pregnancy Outcome in Brahman Cows","authors":"Cecilia Constantino Rocha,&nbsp;Felipe A. C. C. Silva,&nbsp;Ligia Cavani,&nbsp;Andrey Luiz Lopes Cordeiro,&nbsp;Mariangela Bueno Cordeiro Maldonado,&nbsp;Alexandra Bennett,&nbsp;Abdul Waheed,&nbsp;Meghan Campbell,&nbsp;Ky G. Pohler,&nbsp;Francisco Peñagaricano,&nbsp;Mario Binelli","doi":"10.1002/mrd.70047","DOIUrl":"https://doi.org/10.1002/mrd.70047","url":null,"abstract":"<div>\u0000 \u0000 <p>There is a small number of studies describing the uterine biology of <i>Bos indicus</i> cows. We hypothesized that there is a transcriptional signature in endometrial epithelial cells 4 days after estrus (D4) that predicts the ability of the cow to remain pregnant/artificial insemination (AI). Brahman cows were submitted to an estrous synchronization protocol and AI. On D4 cows were submitted to endometrial cytology. Pregnancy/AI was diagnosed on day 30 and endometrial cytology samples were submitted to RNA-seq (<i>n</i> = 32 nonpregnant and <i>n</i> = 32 pregnant). Based on RNA-seq we performed targeted analysis using pathways previously reported in the literature and untargeted analysis using Ingenuity Pathway Analysis. A total of 975 genes were significantly associated (<i>p</i> ≤ 0.1) with pregnancy/AI, 64.9% of them (620/975) showed a negative association. Targeted and untargeted analysis showed a downregulation of Th2 immune response and activation of cholesterol biosynthesis in pregnant cows. Prediction analysis resulted in greater accuracy for the targeted transcripts than the whole transcriptome (0.91 vs. 0.86) but reduced precision (0.64 vs. 0.74). In conclusion, the endometrial receptivity was predominantly marked by an overall reduction in the molecular response. Th2 response and cholesterol biosynthesis are promising pathways to understand uterine biology, and the use of a set of genes rather than a single gene appears to be the future for prediction of pregnancy in bovine.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858615","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":"piR-23 Regulates Porcine Granulosa Cell Apoptosis by Targeting PTGS2","authors":"Jinbi Zhang,&nbsp;Long Huang,&nbsp;Wenjie Li,&nbsp;Xiaolong Cheng,&nbsp;Zengxiang Pan","doi":"10.1002/mrd.70048","DOIUrl":"https://doi.org/10.1002/mrd.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Piwi-interacting RNAs (piRNAs) are small noncoding RNAs that play roles in transposon regulation and gene silencing. Follicular atresia, a process involving granulosa cell (GC) apoptosis, is tightly linked to female reproductive efficiency. Previous studies suggested that piR-23 is differentially expressed in porcine healthy (HF) and early atretic (AF) antral follicles, while prostaglandin-endoperoxide synthase 2 (PTGS2), a key enzyme in prostaglandin biosynthesis, may be a potential target of piR-23. This study investigated whether piR-23 regulates GC apoptosis by targeting PTGS2. Porcine GCs were isolated from HF and AF. piR-23 mimics/inhibitors and PTGS2 siRNA were transfected into GCs to assess cell apoptosis via Annexin V-FITC/PI and CCK-8 assays. Dual-luciferase reporter assays validated the targeting of PTGS2 by piR-23, while qRT-PCR and Western blot analyzed PTGS2 expression. piR-23 expression was downregulated in AF GCs. Overexpression of piR-23 significantly reduced GC apoptosis, whereas inhibition of piR-23 promoted apoptosis. PTGS2 expression was upregulated in AF GCs, and its knockdown suppressed GC apoptosis. Dual-luciferase assays showed that piR-23 directly bound to the 3′UTR of PTGS2, reducing its mRNA and protein levels. Cotransfection of piR-23 inhibitor and PTGS2 siRNA reversed the proapoptotic effect of piR-23 inhibition, confirming PTGS2 as a functional target. piR-23 acts as an antiapoptotic regulator in porcine GCs by directly targeting PTGS2. This finding unveils a novel piRNA-mediated regulatory mechanism in porcine follicular atresia.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832656","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":"Role of Transcription Factor, LIM Homeobox 9 (LHX9) in Inflammatory Response by PGE2 and Thrombin in SERPINA1-Silencing Endometrial Stromal Cells","authors":"Kazuya Kusama,&nbsp;Misuzu Ashihara,&nbsp;Moana Okita,&nbsp;Kanoko Yoshida,&nbsp;Masumi Suzuki,&nbsp;Kaito Suzuki,&nbsp;Rena Hosokawa,&nbsp;Mikihiro Yoshie,&nbsp;Junya Kojima,&nbsp;Yumi Mizuno,&nbsp;Masanori Ono,&nbsp;Hirotaka Nishi,&nbsp;Takeshi Kajihara,&nbsp;Kazuhiro Tamura","doi":"10.1002/mrd.70046","DOIUrl":"https://doi.org/10.1002/mrd.70046","url":null,"abstract":"<p>Endometriosis is hypothesized to result from retrograde menstruation where cell debris including endometrial stromal cells (ESCs) travel through the fallopian tubes. This chronic inflammatory disease is characterized by inflammatory and fibrotic endometrial tissue. We have previously observed reduced expression of the anti-inflammatory factor SERPINA1 in endometriosis-like lesions in a mouse model implanted with human ESCs. Additionally, pro-inflammatory factors present in peritoneal hemorrhage exacerbated inflammation in these grafts, partly through prostaglandin (PG) E2 and thrombin. However, it remains unclear whether the reduction of SERPINA1, in combination with PGE2 and thrombin, synergistically influences the expression of inflammatory factors in endometriosis lesions and the underlying mechanisms. We analyzed RNA sequencing data from ESCs treated with SERPINA1 siRNA and PGE2/thrombin, comparing them to data sets derived from ESCs subjected to either SERPINA1 knockdown or PGE2/thrombin treatment. Comparative analysis identified 49 transcripts that were upregulated under both conditions and enriched for transcription regulatory genes, including SNAI1, HDAC5, PBX1, SOX4, EPAS1, LHX9, and MAFK. Silencing SNAI1, HDAC5, SOX4, EPAS1, or LHX9 suppressed IL6, CXCL8, and IL1B expression, which had been upregulated by SERPINA1 siRNA and PGE2/thrombin. Among these genes, LHX9 expression was significantly elevated in ectopic lesions, predominantly localized to stromal and glandular epithelial cells, with more pronounced expression during the secretory phase. LHX9 levels were also increased in endometriotic lesions compared to the normal endometrium. In conclusion, reduced SERPINA1 expression in ectopic ESCs, combined with PGE2/thrombin, induces inflammatory cytokine expression linked to LHX9. Pharmacological targeting of LHX9 may present a promising therapeutic strategy for mitigating chronic inflammation in endometriotic lesions.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832657","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":"Mechanism of Bushen Shengjing Decoction on the Spermatogenic Function of in Rats With Oligoasthenospermia: Focus on SCF/c-Kit Signaling Pathway-Mediated Apoptosis","authors":"Bo Chen,&nbsp;Hongmei He,&nbsp;Xiaoyan Sun,&nbsp;Qingyang Li,&nbsp;Qiaoyu Yang,&nbsp;Li Zhao,&nbsp;Xueling Li,&nbsp;Guanghui Zhou","doi":"10.1002/mrd.70044","DOIUrl":"https://doi.org/10.1002/mrd.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated the effect of Bushen Shengjing Decoction (BSSJD) to modulate SCF/c-kit signaling pathway-mediated apoptosis on spermatogenesis in rats with oligoasthenospermia (OAS). The glucoside of Tripterygium wilfordii Hook F was given by gavage administration for OAS modeling in rats. The modeled rats were administered by gavage with BSSJD at different doses. Blood was collected from the abdominal aorta. The effect of BSSJD on OAS rats was determined by measuring serum testosterone (T), estradiol (E2) and luteinizing hormone (LH), epididymal index and testicular index, and sperm concentration and viability. Pathological changes in testicular tissues were observed. Caspase-3, Bax and Bcl-2 mRNA levels, along with SCF and c-kit levels in the testis tissues of rats were measured. BSSJD improved sperm concentration and quality, increased T and E2 levels, and reduced LH levels in rats with OAS. BSSJD alleviated apoptosis by decreasing Bax and caspase-3 and increasing Bcl-2 in testicular tissues of rats with OAS. Isck03 reversed the improvement of spermatogenesis and apoptosis in OAS rats treated with BSSJD. BSSJD improves spermatogenic function in OAS rats, which may act by regulating SCF/c-kit signaling pathway-mediated apoptosis.</p>\u0000 </div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809190","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":"microRNAs for qPCR Normalization Under Morphofunctional Conditions in Bovine Sperm (Bos taurus)","authors":"Lucas Petitemberte de Souza,&nbsp;Leandro Silva Nunes,&nbsp;Luana Carla Salvi,&nbsp;Laís dos Santos Gonçalves,&nbsp;Luana Ferreira Viana dos Reis,&nbsp;Izani Bonel Acosta,&nbsp;Carine Dahl Corcini,&nbsp;Antonio Sergio Varela Junior,&nbsp;Fábio Gularte Barreto,&nbsp;Marcelo Brandi Vieira,&nbsp;Diego Corrêa Silveira,&nbsp;Jeaniffer Melgarejo Vieira,&nbsp;Gustavo Freitas Ilha,&nbsp;William Borges Domingues,&nbsp;Vinicius Farias Campos","doi":"10.1002/mrd.70045","DOIUrl":"https://doi.org/10.1002/mrd.70045","url":null,"abstract":"<p>Cattle represents one of the most common and widely distributed categories of large ruminants, with well-established production practices. Fertility is a key factor that significantly influences the success of this production. Studies have shown that microRNAs (miRNAs) present in sperm cells play a crucial role as regulators of processes related to sperm functionality. miRNAs quantification by qPCR is one of the most accurate and straightforward methods, but this technique requires data normalization, and there is no universal consensus on which miRNAs should be used. The present study aimed to identify suitable miRNAs normalizers for qPCR analysis of <i>Bos taurus</i> semen. To achieve this, normalization candidates were assessed under different semen quality conditions, considering sperm morphology and motility. A small nuclear RNA (U6) and six miRNA candidates (Let-7c-5p, miR-100-5p, miR-25-3p, miR-26a-5p, miR-204-5p, miR-92a-3p) were selected. The expression stability of each candidate was analyzed using four independent methods (delta Ct, geNorm, NormFinder, and BestKeeper), under the semen quality conditions. Additionally, a comprehensive stability analysis was conducted using RefFinder, for each condition individually and for the combined conditions. The results indicated that miR-92a-3p was the most stable reference miRNA for motility-related analyses, while Let-7c-5p emerged as the best candidate for morphology-focused analyses. As a normalizer to analyze samples concomitantly, Let-7c-5p was identified as the optimal normalizer, while miR-26a-5p was the least stable candidate. This study provides the first identification of miRNA normalizers for qPCR analysis of <i>Bos taurus</i> semen, enabling more accurate miRNA quantification in this biological matrix and species.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782279","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":"Uncovering the Role of IZUMO Family Members in Human Fertilization","authors":"Ania Antonella Manjon,&nbsp;Gustavo Luis Verón,&nbsp;Sergio A. Garay,&nbsp;Anahi Juarez,&nbsp;Fernanda G. E. de Raffo,&nbsp;Mónica Hebe Vazquez-Levin","doi":"10.1002/mrd.70040","DOIUrl":"https://doi.org/10.1002/mrd.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated IZUMO1, IZUMO2, and IZUMO4 expression, localization, and participation in sperm-oocyte interaction, combining standard biochemical (Western immunoblotting and fluorescence immunocytochemistry) and functional (CPA, HZA, SPA) with computational biology approaches (bioinformatics, protein's 3D-structure modelling). Human IZUMO1, IZUMO2, and IZUMO4 transcripts were found to be testis-enriched (HPA), and expressed since puberty (MeDAS). IZUMO2 and IZUMO4 transcripts levels were lower (<i>p</i> &lt; 0.05) in teratozoospermic men (GEO). Human protein forms of ~40 kDa (IZUMO1), ~23 KDa (IZUMO2) and ~25 KDa (IZUMO4) were specifically immunodetected in sperm extracts. IZUMO proteins were immunolocalized in the acrosomal region of acrosome-intact and acrosome-reacted cells. Sperm pre-incubation with anti-IZUMO antibodies resulted in lower CPA rates using anti-IZUMO4 antibodies, lower HZA rates using anti-IZUMO1, anti-IZUMO2, or anti-IZUMO4 antibodies, and lower SPA rates using anti-IZUMO1 or anti-IZUMO4 antibodies (<i>p</i> &lt; 0.05). IZUMO1 and IZUMO4 were immunodetected in mouse sperm, and antibodies also blocked homologous fertilization. Protein modeling using AlphaFold identified potential antigenic regions recognized by the antibodies used in biological assays, which impaired IZUMO1-JUNO and IZUMO4-JUNO protein interactions. This is the first study that reports human IZUMO1, IZUMO2, and IZUMO4 expression/localization and involvement in gamete interaction. Findings presented enhance our understanding of the molecular interactions leading to fertilization and may contribute to male infertility diagnosis and treatment.</p></div>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773445","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":"Irisin Modulates IFNT Signaling in Bovine Luteal Cells","authors":"Ana Paula da Silva,&nbsp;Karine de Vargas Aires,&nbsp;Suzana Rossato Feltrin,&nbsp;Leonardo Guedes de Andrade,&nbsp;Julia Vieira Cambuí,&nbsp;Carlos Miguel Staudt,&nbsp;Luis Fernando Schütz,&nbsp;Christopher Price,&nbsp;Valério Marques Portela,&nbsp;Alfredo Quites Antoniazzi","doi":"10.1002/mrd.70043","DOIUrl":"https://doi.org/10.1002/mrd.70043","url":null,"abstract":"<p>Adipokines, bioactive proteins derived from adipose tissue, serve as intermediaries between energy status and reproduction, playing pivotal roles in ovarian physiology. Among them, members of the Fibronectin Type III domain-containing the (FNDC) family, including FNDC4 and FNDC5 (the precursor of irisin), have emerged as key modulators of fertility. This study investigated the expression of <i>FNDC4</i>, <i>FNDC5</i>, and their receptors (<i>ITGB1</i>, <i>ITGAV</i>, <i>ADGRF5</i>) across different stages of bovine CL lifespan and evaluated irisin's effects on interferon tau (IFNT)-mediated signaling in bovine luteal cells. The relative abundance of <i>FNDC4</i> and <i>FNDC5</i> mRNA was significantly greater in Early II, Middle, and Late phases when compared to the Early I. The expression of <i>ITGB1</i> and <i>ADGRF5</i> in bovine CL was significantly greater in the Early II, Middle, and Late phases than in the Early I phase, and the abundance of <i>ITGAV</i> mRNA did not differ between the evaluated phases. Also, it was observed that mRNA expression of all evaluated receptors was greater in CL of nonpregnant cows on Day 18 compared to pregnant cows. In vitro experiments demonstrated that irisin treatment enhanced interferon-stimulated genes (ISGs) such as <i>MX1</i> and <i>MX2</i> in luteal cells, suggesting irisin potentiates IFNT signaling. Notably, irisin did not alter steroidogenic enzyme expression or affect cell viability, proliferation, or apoptosis markers, indicating its effects are specific to IFNT signaling pathways. The present study shows that the genes <i>FNDC5</i> and <i>FNDC4</i> are expressed in the bovine corpus luteum at different stages of development and that irisin increased ISGs expression in bovine luteal cells in vitro. The effects of irisin on CL function may be indirect, as plasma irisin increases during the postpartum negative energy balance in dairy cows. We propose that this is part of a compensatory mechanism to modulate IFNT signaling in CL cells and indirectly improve embryonic signaling mechanisms.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"92 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mrd.70043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773444","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}