Reproduction, Fertility, And Development[JOURNAL]
Sun
200 papers
Expression of Sortilin 1-like immunoreactive proteins, an endocytic receptor for pathogenic α-synuclein fibrils, in bovine GnRH neurons: observations in young and aged animals.
Niyonzima YB, Wanjiru DK, Kadokawa H
Reprod Fertil Dev · 2025 Dec · PMID 41292025 · Publisher ↗
CONTEXT: Ageing is associated with reduced fertility, yet the neuronal basis of reproductive decline remains poorly understood. Alpha-synuclein (αSYN), a protein implicated in neurodegeneration, accumulates in bovine gon...
CONTEXT: Ageing is associated with reduced fertility, yet the neuronal basis of reproductive decline remains poorly understood. Alpha-synuclein (αSYN), a protein implicated in neurodegeneration, accumulates in bovine gonadotrophin-releasing hormone (GnRH) neurons during ageing. Sortilin 1 (SORT1), an endocytic receptor for pathogenic αSYN fibrils, may be relevant to this process. AIMS: To examine SORT1 expression in hypothalamic GnRH neurons of young heifers and aged cows, and to assess possible regional and age-related differences. METHODS: SORT1 mRNA and protein were analysed by RT-PCR, quantitative RT-PCR, and western blotting in bovine cortex, hippocampus, and hypothalamic regions, including the preoptic area (POA), arcuate nucleus (ARC), and median eminence (ME). Co-localisation with GnRH was examined by immunofluorescence and confocal microscopy. Expression was also examined in immortalised GnRH neurons (GT1-7). KEY RESULTS: SORT1 transcripts were detected in all brain regions examined and in GT1-7 cells. Western blotting revealed multiple SORT1-like immunoreactive bands in each region, with overall stronger signals in the posterior hypothalamus (ARC and ME) of aged cows. Transcript levels showed no clear age-related differences. Confocal microscopy demonstrated SORT1-like immunoreactivity in GnRH-positive neurons in both age groups. CONCLUSION: Bovine GnRH neurons express SORT1-like immunoreactivity, indicating the presence of proteins related to SORT1 in these cells. The multiple immunoreactive bands observed may reflect isoforms, processing, or antibody cross-reactivity; however, their identities remain to be confirmed. IMPLICATIONS: These findings provide evidence for SORT1-like expression in bovine GnRH neurons, forming a basis for future studies on its potential role in reproductive ageing.
Extended embryo culture: illuminating a black box of early development in ruminants.
Martínez de Los Reyes N, Siegmund-Sabater A, Flores-Borobia I … +5 more , González-Brusi L, Salvo-Jiménez A, Marigorta P, Bermejo-Álvarez P, Ramos-Ibeas P
Reprod Fertil Dev · 2026 Jan · PMID 41292015 · Publisher ↗
Pregnancy losses due to early embryonic mortality remain a major concern in farm ungulates, including cattle, sheep, pigs and goats. The majority of these losses occur during conceptus elongation, a developmental phase u...
Pregnancy losses due to early embryonic mortality remain a major concern in farm ungulates, including cattle, sheep, pigs and goats. The majority of these losses occur during conceptus elongation, a developmental phase unique to ungulates that follows blastocyst hatching. This stage entails complex cell differentiation, proliferation and migration processes, leading to a rapid expansion of the extraembryonic membranes (EEMs), namely the trophoblast and the hypoblast, and the formation of the embryonic disc (ED) from the epiblast. Despite its biological and economic relevance, the molecular mechanisms regulating embryo development beyond the blastocyst stage, particularly those governing the ED formation, remain poorly understood. Fortunately, recent advances in extended culture systems are enabling the study of these processes entirely in vitro, reducing the need for experimental animals. In this review, we highlight key interspecies differences in early embryogenesis across mammalian species. We discuss the progression and refinement of extended embryo culture systems, from early pioneering efforts to the latest advances, with a specific focus on ruminant species, including cow and sheep. Lastly, we review recent functional studies leveraging extended embryo culture systems in ruminants to elucidate the molecular pathways controlling post-hatching development.
Gene editing and multi-omics approaches to study early embryogenesis in cattle.
Chen C, Kassim Y, Xu X … +7 more , He X, Lin H, Dang Y, Shi Y, Wang H, Wang S, Zhang K
Reprod Fertil Dev · 2026 Jan · PMID 41292010 · Publisher ↗
Advancements in multi-omics profiling and targeted molecular functional tools have led to significant progress in our understanding of early embryonic development in mammals. This is very relevant in the beef and dairy i...
Advancements in multi-omics profiling and targeted molecular functional tools have led to significant progress in our understanding of early embryonic development in mammals. This is very relevant in the beef and dairy industries for exploring the etiology of early embryo loss. This review highlights how state-of-the-art single-cell and integrative low-input omics technologies, including single-cell RNA-seq, ATAC-seq, metabolomics, and proteomics, have uncovered complex developmental dynamics during the first week of bovine embryogenesis. This review also provides a concurrent overview of the application of functional tools, including CRISPR-Cas9, RNA editing, base editing, and Trim-Away, in the analysis of critical genes/proteins during the various stages of early embryo development in cattle. The integration of high-dimensional molecular profiling with targeted manipulations enables researchers to analyze key developmental events with unparalleled resolution. It is evident that these approaches provide a more comprehensive mechanistic depiction of early embryogenesis, thereby informing translational efforts in improving bovine fertility.
Heterospermic semen: implications for managing bull-to-bull variation in fertility.
Santos RM, Fair S
Reprod Fertil Dev · 2026 Jan · PMID 41292006 · Publisher ↗
Heterospermic (HS) bull semen involves mixing the semen from two or more sires in the same semen straw. It has the potential to protect against sub-fertile bulls which pass semen quality control checks, due to the presen...
Heterospermic (HS) bull semen involves mixing the semen from two or more sires in the same semen straw. It has the potential to protect against sub-fertile bulls which pass semen quality control checks, due to the presence of sperm from other males in the same straw. Previous studies suggest that its use could increase conception rates due to a more heterogeneous population of sperm in the female reproductive tract. Despite increasing use of HS semen in the recent years, driven mainly by the introduction of sex-sorted semen and increased usage of HS beef semen on dairy cows, few studies have focused on the physiological mechanisms underpinning its fertility. This review aims to summarize the existing studies on HS bull semen, present hypotheses for its potential role in sperm interaction with the female reproductive tract, introduce the topic of HS sex-sorted semen and, finally, discuss the challenges for the large-scale production and implementation of this product in breeding programs.
External factors influencing reproductive tract microbiota in cattle.
Poole RK
Reprod Fertil Dev · 2026 Jan · PMID 41292005 · Publisher ↗
Historically, bacteria identified within the reproductive tract of cattle using culture-based techniques were associated with disease. Indeed, bacterial genera including Fusobacterium, Bacteroides, Prevotella, and Porphy...
Historically, bacteria identified within the reproductive tract of cattle using culture-based techniques were associated with disease. Indeed, bacterial genera including Fusobacterium, Bacteroides, Prevotella, and Porphyromonas identified by sequencing technology within the reproductive tract are indicative of the development of postpartum reproductive diseases including metritis and clinical endometritis. However, alongside culture-based methods and disease diagnosis, recent sequencing technology and bioinformatic analyses have also expanded our understanding of normal, healthy reproductive tract microbiota in cattle. Recent evidence suggests that microbiota in the reproductive tract may also play a vital role in fertility. Therefore, this review highlights our current understanding of microbiota in reproductive tissues such as the vagina, cervix, uterus, and placenta in cattle as well as describes factors such as estrous synchronization/hormonal influence, heat stress, and diet/nutritional status on shifting the composition of the reproductive tract microbiota.
Exploring the potential of prepubertal oocytes: a small ruminant model.
Paramio MT, Ferrer-Roda M, Izquierdo D … +1 more , Mogas T
Reprod Fertil Dev · 2026 Jan · PMID 41292004 · Publisher ↗
Juvenile in vitro embryo transfer (JIVET) employs oocytes from prepubertal females to reduce generation intervals. In human, it offers potential applications for fertility preservation in young cancer patients. Ruminant...
Juvenile in vitro embryo transfer (JIVET) employs oocytes from prepubertal females to reduce generation intervals. In human, it offers potential applications for fertility preservation in young cancer patients. Ruminant animals are good models for human research because of similar follicular dynamics and oocyte competence. Several studies have shown low embryo development of prepubertal oocytes. However, oocytes from follicles larger than 3 mm can develop into blastocysts at rates comparable to oocytes from adults. This review analyzes biomarkers of oocytes as a function of follicle size (larger or smaller than 3 mm). Follicular fluid from prepubertal females contains lower levels of n-3 fatty acids than that of adults; expression of epidermal growth factor receptor (EGFR) receptor in cumulus cells is higher in large than small follicles; the condensed germinal vesicle (GV) configuration is similar in prepubertal females to the adult ones, and prepubertal large follicles and oocytes are more susceptible to oxidative stress than adult ones. In vitro maturation (IVM) strategies have been investigated: capacitation IVM (CAPA-IVM) increases EGF receptor expression and promotes GV compaction; supplementation with bone morphogenetic protein 15 (BMP15) increases EGF receptor expression; and addition of antioxidants to IVM is essential. In conclusion, oocyte competence seems to be more related to follicular state than to female age, highlighting the importance of follicular selection and optimization of IVM conditions for improving JIVET outcomes.
When less really is more: reducing embryo manipulation to lower metabolic stress and improving long term outcomes.
Rinaudo P, Simbulan R
Reprod Fertil Dev · 2026 Jan · PMID 41291996 · Full text
The use of assisted reproductive technologies (ARTs) to treat human infertility has increased exponentially in recent years. In addition to improved access to care for infertile patients, there is a significant increase...
The use of assisted reproductive technologies (ARTs) to treat human infertility has increased exponentially in recent years. In addition to improved access to care for infertile patients, there is a significant increase in ART utilization in individuals without infertility, who electively chose to freeze their gametes and embryos for future use. Importantly, the number of procedures performed on eggs (egg freezing and thawing, increase in intracytoplasmic sperm injection (ICSI) utilization) and embryo (embryo biopsy for preimplantation genetic testing (PGT), freezing and thawing) has also increased over time. Here we review the laboratory animal evidence indicating how an increase in the number of procedures performed may be associated with increase in embryonic stress, altered in utero growth and possible neonatal and long-term consequences. These data suggest that minimizing the number of gamete and embryo procedures to the minimum required is a wise approach, while waiting for human data to provide further guidance.
Embryonic HBEGF regulates FoxO1 through PI3K signaling as embryo breaches maternal epithelial barrier.
Adiguzel D, Sati L, Celik-Ozenci C
Reprod Fertil Dev · 2026 Jan · PMID 41291994 · Publisher ↗
CONTEXT: The initial barrier encountered by the embryo during the pivotal phase of implantation and subsequent pregnancy maintenance is the maternal endometrial epithelial barrier. AIMS: To elucidate the interaction betw...
CONTEXT: The initial barrier encountered by the embryo during the pivotal phase of implantation and subsequent pregnancy maintenance is the maternal endometrial epithelial barrier. AIMS: To elucidate the interaction between the forkhead Box O1 (FoxO1) molecule, which is present in the endometrial luminal epithelium during mouse embryo implantation, and the embryonic heparin binding epidermal growth factor (HBEGF) and phosphoinositide 3-kinase (PI3K) signaling pathways, along with their potential roles in modulating the epithelial barrier. METHODS: A normal pregnancy group and a pseudopregnancy model established through uterine bead transfer using bovine serum albumin (BSA)- or HBEGF-coated beads with or without the PI3K inhibitor (Wortmannin) were analyzed by comprehensive immunofluorescence, providing insights into the distinct expression patterns and probable functions of HBEGF and FoxO1 within the endometrial milieu. RESULTS: Pharmacological inhibition of PI3K by Wortmannin suppresses HBEGF expression and disrupts FoxO1 signaling in the luminal epithelium, leading to nuclear accumulation of FoxO1 in the crypt epithelium and ultimately preventing luminal closure, required for implantation. CONCLUSIONS: This research underscores the critical role of PI3K, HBEGF, and FoxO1 signaling in facilitating the embryo's ability to breach the epithelial barrier during implantation.
Towards understanding mare endometrosis: ex vivo study on the role of relaxin.
Profaska M, Zarzycka M, Dubniewicz K … +6 more , Witkowski M, Wieczorek J, Gil D, Wafula S, Lanh DK, Kotula-Balak M
Reprod Fertil Dev · 2025 Dec · PMID 41291992 · Publisher ↗
CONTEXT: Mare endometrosis remains a poorly understood pathological process. AIMS: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H...
CONTEXT: Mare endometrosis remains a poorly understood pathological process. AIMS: Mare endometrial tissue with endometrosis was used to determine the effects of relaxin (RLX). Healthy tissues that were left untreated (H), or treated with vehicle (Hveh), and tissues with endometrosis that were left untreated (E), treated with vehicle (Eveh), and treated with RLX (10, 25, 50 nM; ER) were used for an ex vivo system for 72 h. METHODS: Tissue histological examination, and immunoenzymatic measurement of the concentrations of transforming growth factor β (TGF-β), interleukins (IL-6 and IL-8), and progesterone were performed. Western blotting was used to study the abundance of the following proteins involved in cellular processes, signaling, and interactions: N-cadherin, cortactin, Wnt/β-catenin signaling with kinases: glycogen synthase kinase-3β (GSK-3β), protein kinase B (AKT), metalloproteinases: MMP9, MMP2, and cyclins: D1, D3. KEY RESULTS: RLX (50 nM) decreased the concentration of TGF-β, increased concentrations of IL-6 and IL-8, and decreased the concentration of progesterone, without histological alterations of the treated tissues. Interactions of RLX with proteins showed changes in protein abundance, as follows: N-cadherin increased, cortactin increased, β-catenin, GSK-3β and AKT showed an increase of phosphorylation, MMP2 and MMP9 increased, and cyclin D3 increased in ER versus E. CONCLUSIONS: Results indicated that RLX exerted both anti-/pro-inflammatory as well as anti-/pro-fibrotic effects depending on interacting cytokine/protein. IMPLICATIONS: In equine breeding, the application of RLX with marker protein antagonists/agonists may be promising in endometrial fibrosis treatment.
Guanidinoacetic acid supplementation negatively affects bovine cumulus-oocyte complexes during in vitro maturation.
Snider AP, Kaps M, Rempel LA … +3 more , Miles JR, Cushman RA, Crouse MS
Reprod Fertil Dev · 2025 Dec · PMID 41291986 · Publisher ↗
CONTEXT: Methylation is an important part of oocyte maturation and early embryonic development. Altered methylation status leads to poor oocyte quality and altered embryonic development. One specific metabolite, guanidin...
CONTEXT: Methylation is an important part of oocyte maturation and early embryonic development. Altered methylation status leads to poor oocyte quality and altered embryonic development. One specific metabolite, guanidinoacetic acid (GAA), sequesters methyl-groups to make creatine, causing a methyl deficient state. Understanding how GAA influences oocyte methylation status increases knowledge of oocyte maturation in vitro. AIMS: The objective of this study was to determine the threshold concentration of GAA supplementation negatively impacting oocyte quality. We hypothesized that supplementation of GAA reduces quality of oocytes and alters early embryonic development in a dose dependent manner. METHODS: Immature cumulus oocyte complexes were collected from slaughterhouse ovaries and matured in vitro with GAA (0 mM, 5 mM, 10 mM or 20 mM) incorporated into the medium. Matured oocytes were randomly collected to determine microtubule distribution and transcriptomic analysis, or fertilized and developed embryos in vitro. KEY RESULTS: Incorporation of GAA during in vitro maturation negatively impacted oocyte quality and early embryonic development. Specifically, supplementation of 5 mM GAA reduced S-adenosyl-L-methionine production (P < 0.05), increased transcripts within the creatine pathway in oocytes (P < 0.05) and impaired chromosome arrangement (P < 0.05). Reduction in total cells was observed in blastocysts from the 5 mM and 20 mM GAA group. CONCLUSIONS: Incorporation of 5 mM GAA to the in vitro maturation medium negatively impacted oocyte and subsequent early embryonic development. The 20 mM supplementation demonstrated negative implications, but the methylation pathway was not impacted. IMPLICATIONS: Further research is warranted to investigate other potential mechanisms that are impacted by eliciting a methyl donor deficient status in matured oocytes.
Translational pig models for human diseases.
Wolf E, Ali A, Blasi M … +14 more , Blutke A, Deeg CA, Fröhlich T, Hinrichs A, Hristov H, Jaudas F, Kemter E, Keßler B, Klymiuk N, Kurome M, Matiasek K, Nagashima H, Renner S, Zakhartchenko V
Reprod Fertil Dev · 2026 Jan · PMID 41291984 · Publisher ↗
The translation of novel discoveries in biomedical research into clinical applications is a lengthy and resource-intensive process, with variable success. Predictive model organisms for non-clinical research are a key as...
The translation of novel discoveries in biomedical research into clinical applications is a lengthy and resource-intensive process, with variable success. Predictive model organisms for non-clinical research are a key asset in this process. Rodents remain the most widely used models, but they have limitations in recapitulating human pathophysiology and disease phenotypes. Over the past two decades, pigs have played an increasingly important role in bridging this translational gap. Given their close anatomical and physiological similarity to humans, most vividly illustrated by successful pig-to-human organ xenotransplantation, pigs provide unparalleled advantages for translational research. Advances in genetic engineering now allow the precise recreation of human disease mechanisms in pigs, generating tailored large-animal models with exceptional clinical relevance. This review highlights the potential of genetically modified pig models for human diseases, with a focus on metabolic disorders and rare monogenic diseases such as Duchenne muscular dystrophy, cystic fibrosis, and Laron syndrome.
Prenatal development of the intramural vascular system of the uterine tube in the European shorthair cat.
Prozorowska-Basińska E, Jackowiak H
Reprod Fertil Dev · 2025 Dec · PMID 41291980 · Publisher ↗
CONTEXT: Early vascular development during the prenatal period is essential for the proper formation of all organs, including the reproductive system. AIMS: This study aimed to characterize the development of the intramu...
CONTEXT: Early vascular development during the prenatal period is essential for the proper formation of all organs, including the reproductive system. AIMS: This study aimed to characterize the development of the intramural vascular system in the domestic cat's uterine tube, with emphasis on changes associated with wall layer formation. METHODS: Uterine tubes from 38 domestic cat fetuses (36-63 days post-conception) were examined using light microscopy, vascular corrosion casts, and scanning electron microscopy. KEY RESULTS: In early stages, the vascular system of the rudimentary paramesonephric duct (uPD) is simple, comprising longitudinal vessels and a superficial vascular network. Initially, all vessels resemble capillaries. By Days 42-43 post-conception, vascular differentiation into arterioles and venules becomes evident, progressing to arteries and veins with distinct surface relief visible on corrosion casts by late gestation. Approximately by Day 50 post-conception, as the layers develop in the uterine tube wall, a subepithelial capillary network emerges, connecting with the superficial vascular system. At term, the uterine artery becomes tortuous and branches above the isthmus; veins accompany the arteries. The mature intramural vascular system includes circumferential arteries and veins, as well as subepithelial and subserosal capillary networks. CONCLUSIONS: A basic vascular architecture supporting tissue growth develops prenatally, laying the foundation for postnatal expansion linked to mucosal and muscular layer maturation. IMPLICATIONS: This first-time analysis of feline uterine tube prenatal angioarchitecture provides novel insights into reproductive system histogenesis in a species both common in human environments and important in veterinary science.
Gene expression changes in male germ cells differ following in vivo versus in vitro exposure to hyperthermia.
Robinson BR, Netherton JK, Ogle RA … +3 more , Williams GE, Tennant GM, Baker MA
Reprod Fertil Dev · 2025 Nov · PMID 41265870 · Publisher ↗
CONTEXT: Testicular heat stress is a well-established disruptor of spermatogenesis, yet the immediate transcriptional responses in heat-sensitive germ cells remain poorly understood. AIMS: To investigate the transcriptio...
CONTEXT: Testicular heat stress is a well-established disruptor of spermatogenesis, yet the immediate transcriptional responses in heat-sensitive germ cells remain poorly understood. AIMS: To investigate the transcriptional responses of isolated spermatocytes and round spermatids to heat stress, comparing in vivo and in vitro models. METHODS: We employed two methods of testicular hyperthermia, an in vivo (water bath) and an in vitro (isolated cell) model, and analysed transcriptional changes in spermatocytes and round spermatids. These were compared with in vitro heat responses in somatic cell lines (NIH3T3, B16F10 and TM4 cells). Transcriptional responses were assessed by real-time quantitative polymerase chain reaction (PCR). KEY RESULTS: In vivo heat stress resulted in significant upregulation of heat-responsive genes (Hspa1a and Hsph1), the long non-coding RNA 4930555K19Rik, and transposable element LINE1. However, in vitro heat stress showed only minimal induction of Hspa1a and failed to replicate the broader transcriptional responses observed in vivo. Somatic cell lines demonstrated greater heat shock gene activation than isolated primary germ cells following in vitro heat exposure. CONCLUSIONS: The results suggest that the testicular microenvironment plays a critical role in the transcriptional response to heat stress. Isolated germ cells may not adequately represent the molecular response to testicular hyperthermia. IMPLICATIONS: These results have provided new insight into the molecular basis of male germ cell heat sensitivity, with implications for fertility preservation under environmental or occupational heat exposure. Understanding the dependence of transcriptional responses on the testicular microenvironment could guide future interventions to protect spermatogenesis and inform assisted conception in humans and livestock.
The location of a translocation breakpoint, rather than fragment size, is associated with spermatogenic function.
Wang Y, Han Y, Zheng Y … +5 more , Hao Y, Shao M, Chang L, Wang Y, Huang J
Reprod Fertil Dev · 2025 Nov · PMID 41260616 · Publisher ↗
CONTEXT: Male carriers of balanced reciprocal translocations can experience impaired spermatogenesis and adverse pregnancy outcomes. The impact of translocation fragment size and breakpoint location on these outcomes rem...
CONTEXT: Male carriers of balanced reciprocal translocations can experience impaired spermatogenesis and adverse pregnancy outcomes. The impact of translocation fragment size and breakpoint location on these outcomes remains unclear. AIMS: To investigate whether the location and size of translocated fragments relate to spermatogenic function, embryo aneuploidy ratio, and pregnancy outcomes in couples with male chromosomal translocation. METHODS: In total, 103 couples with male reciprocal translocation were included and these couples underwent 116 pre-implantation genetic testing cycles. Patients were divided into Group A (at least one translocation segment size <10 Mb) and Group B (both segment sizes ≥10 Mb) to compare the association of translocation segment size on spermatogenic function, embryo aneuploidy ratio, and pregnancy outcomes. Additionally, patients were categorized into Group I (normal/mild-moderate oligospermia) and Group II (severe oligospermia) on the basis of sperm concentration, to compare the relationship of translocation breakpoint position on semen output. KEY RESULTS: No significant differences were found between Groups A and B in the proportion with severe oligozoospermia (26.47% vs 21.74%), euploid blastocyst rate (35.64% vs 36.18%), or cumulative pregnancy rate (42.11% vs 55.26%). However, the proportion of couples with 1q fragment was significantly higher in Group II than in Group I (16.28% vs 3.25%). CONCLUSIONS: The size of male autosomal translocation fragments is not significantly associated with sperm concentration or pregnancy outcomes, although translocations involving the 1q fragment may relate to spermatogenic dysfunction. IMPLICATIONS: Genetic counseling for male translocation carriers should prioritize breakpoint location, particularly on 1q, over fragment size when evaluating spermatogenic impairment risk.
Corrigendum to: Reconstruction of endometrial histoarchitecture and receptivity genes in Asherman's syndrome patients using a 3D acellular amnion bilayer scaffold seeded with endometrial cells.
Wiweko B, Sandora N, Raden M … +10 more , Harzif AK, Kusuma TR, Fitria NA, Karimah B, Maidarti M, Sumapraja K, Hestiantoro A, Pratama G, Priangga MD, Law NK
Reprod Fertil Dev · 2025 Oct · PMID 41253136 · Publisher ↗
Abstract loading — click title to view on PubMed.
Genistein mitigates ovarian dysfunction in a PCOS mouse model by regulating steroidogenesis, apoptosis, and PARP-1 signaling.
Wang J, Lu F, Guo Z … +7 more , Meng Q, Gou T, Li W, Wan X, Akhta MF, Azzam MM, Wu G
Reprod Fertil Dev · 2025 Oct · PMID 41253135 · Publisher ↗
CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder marked by hormonal and clinical imbalances. Genistein (GEN), a soy isoflavone with antioxidant properties, has shown promise in PCOS treatment, alt...
CONTEXT: Polycystic ovary syndrome (PCOS) is a common endocrine disorder marked by hormonal and clinical imbalances. Genistein (GEN), a soy isoflavone with antioxidant properties, has shown promise in PCOS treatment, although its mechanisms remain unclear. AIMS: This study aimed to investigate the effects of genistein on ovarian dysfunction in a letrozole-induced PCOS mouse model, focusing on steroidogenesis, apoptosis, and PARP-1 signaling. METHODS: PCOS was induced by oral administration of letrozole (37.5 mg/kg.day) for 21 days. Mice were then divided into the following three groups (n = 10 each) for another 21-day treatment: control (corn oil), PCOS (continued letrozole), and PCOS + GEN (letrozole + genistein, 50 mg/kg.day, i.p.). KEY RESULTS: Genistein restored estrous cyclicity in 80% of treated mice versus 0% in the PCOS group (P < 0.05). Histologically, it improved follicular morphology, increased granulosa cell thickness and density, and promoted corpora lutea formation. Genistein significantly reduced serum T and P4 concentrations (P < 0.05) and modulated expression of steroidogenic proteins (CYP11A1, CYP19A1, STAR). It also decreased cleaved Caspase-3 and cleaved PARP-1 expression (P < 0.05), and suppressed abnormal PARylation without affecting total PARP-1 expression levels. CONCLUSIONS: Genistein alleviates ovarian dysfunction in PCOS mice by restoring estrous cyclicity, enhancing follicular development, and normalizing hormone concentrations, through regulation of steroidogenic proteins, inhibition of apoptosis, and modulation of PARP-1 activity. IMPLICATIONS: These findings support genistein as a potential therapeutic agent for PCOS, targeting the PARP-1-pADPr axis and apoptosis. Further studies are needed to explore upstream mechanisms and evaluate its long-term effects on reproductive health.
Platelet-rich plasma strategy against freezing damage in ram spermatozoa: its effect on miRNA, ion channels, growth factors, lipids and oxidative stress.
Güngör İH, Türk G, Çakır Cihangiroğlu A … +13 more , Arkalı G, Tektemur A, Kırmızıkaya Özmen G, Badıllı N, Acısu TC, Bulan MS, Özer Kaya Ş, Sönmez M, Gür S, Yüce A, Yilmaz Ö, Memili E, Çambay Z
Reprod Fertil Dev · 2025 Oct · PMID 41253134 · Publisher ↗
CONTEXT: Platelet-rich plasma (PRP) is a plasma component containing high concentrations of platelets, growth factors, antioxidants and proliferative properties. AIM: To mitigate the negative effects of cryopreservation...
CONTEXT: Platelet-rich plasma (PRP) is a plasma component containing high concentrations of platelets, growth factors, antioxidants and proliferative properties. AIM: To mitigate the negative effects of cryopreservation on ram semen by utilising PRP. METHODS: Semen was collected from six rams twice a week for 3 weeks during the breeding season. Pooling was performed by dilution with tris + egg yolk diluent. Pooling was divided into three equal parts and re-diluted with diluents containing control (0% PRP), 5% PRP and 10% PRP. Sperms were frozen in an automatic freezing device and stored in liquid nitrogen. After thawing, spermatological, flow-cytometric, oxidative stress, cholesterol, fatty acid, ELISA, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were performed. KEY RESULTS: Compared with the control group, the 5% PRP group exhibited a significant increase in progressive motility, viability and cholesterol ratios, glutathione-peroxidase activity, CATSPER1 (Cation Channel of Sperm), CATSPER3, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels and KCNJ11 (Potassium Channel, Inwardly Rectifying, Subfamily J, Member 11), HSA-MIR-181A, HSA-MIR-150 and HSA-MIR-374 transcripts. Apoptotic protein, malondialdehyde and HSA-MIR-410, OAR-MIR-10B, BTA-MIR-22-3P and RNO-MIR-494 transcripts were decreased in 5% PRP group compared with control. PRP supplementation at 10% increased dead sperm and heptadecenoic acid ratios, VEGF and PDGF levels and HSA-MIR-410, PPY-MIR-16, CFA-MIR-199, HSA-MIR-181A, HSA-MIR-150, OAR-MIR-127, HSA-LET-7A and HSA-MIR-374 transcripts as well as CATSPER3, HSD3β2, PDGFB and VEGFA proteins compared with the control. PRP supplementation at 10% significantly decreased plasma membrane integrity, insulin-like growth factor 1 (IGF1) level and CATSPER3 and KCNJ11 transcripts compared with the control. CONCLUSIONS: The addition of 5% PRP before cryopreservation has beneficial effects on the functional and molecular properties of frozen-thawed ram spermatozoa, whereas the addition of 10% PRP has negative effects. IMPLICATIONS: Five per cent PRP should be added to ram semen diluents.
Sperm interaction in the hyperandrogenized female reproductive tract might contribute to female infertility: a hypothesis.
Lalrawngbawli A, Kaur N, Gurusubramanian G … +2 more , Kharwar RK, Roy VK
Reprod Fertil Dev · 2025 Nov · PMID 41232963 · Publisher ↗
It is well known that hyperandrogenism (HA) in females is associated with oligo-ovulation or anovulation, leading to subfertility. The abnormality in ovulation is due to ovarian dysfunction. However, it remains unclear w...
It is well known that hyperandrogenism (HA) in females is associated with oligo-ovulation or anovulation, leading to subfertility. The abnormality in ovulation is due to ovarian dysfunction. However, it remains unclear whether ovarian dysfunction is the sole cause of subfertility. The crosstalk between sperm and the hyperandrogenized female reproductive tract has yet to be explored in the context of subfertility or infertility. Therefore, in the present paper, we hypothesized that firm sperm binding to the hyperandrogenized female reproductive tract might be one of the reasons for subfertility. The sperm binding to the hyperandrogenized female tract could delay the capacitation, thereby preventing timely sperm release from the tract, even in the presence of a viable ovum. This way the sperm binding to female tract may augment to infertility in the females with high androgen concentrations.
Relationship between plasma sex steroids and cell proliferation-related gene expression in the uterus during dioestrus in nonpregnant bitches.
Gossler VDSA, Nunes SG, Garcia Santos FA … +8 more , de Oliveira Santos A, Mattoso Miskulin Cardoso AP, Papa PC, Marçal NCO, de Souza LFA, Castilho C, Floriano RS, Giometti IC
Reprod Fertil Dev · 2025 Nov · PMID 41207785 · Publisher ↗
CONTEXT: Reproductive processes in mammals involve complex interactions between sex steroids and growth factor systems. Understanding these interactions in the uterus during different stages of the reproductive cycle is...
CONTEXT: Reproductive processes in mammals involve complex interactions between sex steroids and growth factor systems. Understanding these interactions in the uterus during different stages of the reproductive cycle is essential for elucidating the mechanisms of endometrial regulation. AIMS: This study aimed to investigate the relationship between circulating sex steroids and the expression of genes involved in the insulin-like growth factor 1 (IGF1) system and steroid hormone receptors in the uterine horns of non-pregnant bitches during dioestrus. METHODS: Uterine horns from 29 bitches were collected surgically at 10, 20, 30, 40, 50, and 60 days post-ovulation (n = 4 or 5 per group). Relative mRNA abundances of IGF1 system genes (IGF1, IGFR1, IGFBP3, IGFBP4, PAPPA) and steroid hormone receptors (PGR, ESR1, ESR2) were determined by RT-qPCR. Blood samples collected at surgery were analysed for oestradiol and progesterone concentrations. Correlations between hormone levels and gene expression were assessed. KEY RESULTS: ESR2 gene expression declined at 40 and 50 days post-ovulation compared to 30 days or earlier, and was positively correlated with progesterone and negatively with the oestradiol/progesterone ratio. IGFBP3 expression increased progressively through dioestrus, while IGFBP4 expression rose at the later stages (50 and 60 days), showing a negative correlation with progesterone and a positive correlation with the oestradiol/progesterone ratio. CONCLUSIONS: Reduced ESR2 gene expression at 40 days of dioestrus may reflect a uterine environment permissive to local cell proliferation, suggesting dynamic hormonal modulation of endometrial responsiveness. IMPLICATIONS: The gradual increase in IGFBP3 and IGFBP4 gene expression throughout dioestrus indicates a potential role for these binding proteins as modulators of IGF1 bioavailability, contributing to the fine-tuning of uterine tissue remodelling in non-pregnant bitches.
The impact of obesogenic disturbances on in vitro fertilization outcomes in a Mexican population.
Reyes-Albarracín Y, Porchia LM, Gonzalez-Mejia ME … +1 more , López-Bayghen E
Reprod Fertil Dev · 2025 Nov · PMID 41193945 · Publisher ↗
CONTEXT: Overweight and obese patients tend to have more difficulty getting pregnant through in vitro fertilization (IVF), but it is still unclear whether this effect varies by ethnicity and age. AIMS: To assess the effe...
CONTEXT: Overweight and obese patients tend to have more difficulty getting pregnant through in vitro fertilization (IVF), but it is still unclear whether this effect varies by ethnicity and age. AIMS: To assess the effect obesity has on IVF among infertile, advanced-age (≥ 35 years) Mexican women. METHODS: Retrospectively, data were collected from the INGENES Institute (2018-2022; n = 2,232). Pearson's correlation coefficient (r) was calculated to evaluate associations. The area under the receiver operating characteristic curve (AUC) determined the predictability of body mass index (BMI) for IVF with the highest Youden index score (sensitivity + specificity - 1) as the optimal cutoff value. Logistic regression was used to calculate risk (odds ratios (ORs) with 95% confidence intervals (95%CIs)). KEY RESULTS: BMI was negatively correlated with IVF outcomes (P < 0.001): biochemical pregnancy (r = -0.164), clinical pregnancy (r = -0.188), and live birth (r = -0.202). BMI cutoffs to predict IVF success were: ≤ 25.1 kg/m2 for biochemical pregnancy (AUC = 0.63; specificity = 71.4%; sensitivity = 50.1%); ≤ 24.0 kg/m2 for clinical pregnancy (AUC = 0.65; specificity = 85.3%; sensitivity = 40.2%), and ≤ 24.0 kg/m2 for live birth (AUC = 0.67; specificity = 85.7%; sensitivity = 44.4%). Overweight or obese patients had higher risks of not having transferable embryos (OR = 2.7, 95%CI: 2.1-3.4 and OR = 3.8, 95%CI: 2.5-5.6, respectively, P < 0.001) and failed embryo implantation (OR = 3.1, 95%CI: 2.3-3.9 and OR = 4.7, 95%CI: 3.2-7.1, respectively, P < 0.001). The risk of pregnancy loss was also higher in patients who were overweight (OR = 4.7, 95%CI: 2.4-9.4, P < 0.001) and obese (OR = 4.0, 95%CI: 1.5-10.8, P = 0.006). CONCLUSION: BMI was highly associated with and predicted IVF failure. IMPLICATIONS: Obesity is a prevalent factor that affects each stage of IVF; diet and other weight management treatments need to be implemented to promote IVF success.
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