Reproduction, Fertility, And Development[JOURNAL]
Sun
200 papers
Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts.
Słyszewska M, Guerreiro M, Sadowska A … +3 more , Jaworska J, Ferreira-Dias G, Szóstek-Mioduchowska A
Reprod Fertil Dev · 2026 Jul · PMID 42393018 · Publisher ↗
CONTEXT: Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a...
CONTEXT: Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. AIMS: The objective of this study was to determine: (i) the expression of IL-12 and its receptor in different mare endometrial categories; (ii) the effects of IL-12 on the expression of ECM-related factors; and (iii) endometrial fibroblast functional characteristics. METHODS: The mRNA expression of IL-12 subunits and IL-12 receptor was determined using quantiative polymerase chain reaction (qPCR). The expression of ECM-related factors and functional characteristics in endometrial fibroblasts were determined using qPCR, Western blotting, zymography with bromodeoxyuridine and scratch assays. KEY RESULTS: IL-12Rβ2 mRNA expression was upregulated in category IIB endometrium during the mid-luteal phase compared with the follicular phase of the estrous cycle. The IL-12 treatment of endometrial fibroblasts increased mRNA expression of COL1A1, COL3A1, ACTA2, and LOXL2, as well as matrix metalloproteinase (MMP)-9 and MMP3, with elevated pro-MMP2 and MMP9 gelatinolytic activity. Moreover, IL-12 reduced fibroblast proliferation after 96 h, without effect on migration. CONCLUSIONS: The findings indicate that IL-12 has a direct impact on the mRNA expression of fibrotic markers, MMP-2 and MMP-9 gelatinolytic activity and fibroblast proliferation. IMPLICATIONS: This suggests a potential role for IL-12 in the processes associated with ECM remodeling.
CRH expression and function in mouse uterus during early pregnancy.
Shen QM, Liu L, Wang ZM … +2 more , Fu QT, Yang ZM
Reprod Fertil Dev · 2026 Jul · PMID 42331344 · Publisher ↗
CONTEXT: Embryo implantation and decidualization are essential to the establishment and maintenance of pregnancy. However, the underlying mechanism on embryo implantation and decidualization remains unclear. Although the...
CONTEXT: Embryo implantation and decidualization are essential to the establishment and maintenance of pregnancy. However, the underlying mechanism on embryo implantation and decidualization remains unclear. Although the regulation and role of hypothalamic corticotropin-releasing hormone (CRH) during early pregnancy have been extensively studied, uterine CRH is still poorly defined. AIMS: This study examined CRH expression in mouse uterus during early pregnancy and evaluated the regulation and role of CRH during embryo implantation and decidualization. METHODS: Immunofluorescence was used to show CRH protein concentrations in mouse uterus. The inhibitor for CRH receptor CRHR1 and recombinant CRH protein were applied to analyze the function of CRH on mouse in vitro decidualization. KEY RESULTS: CRH is expressed in luminal epithelium of mouse uterus from Day 1 to Day 4 of pregnancy. At implantation site on Day 5 of pregnancy, CRH is strongly localized in primary decidua. Verucerfont, a CRHR1 inhibitor, significantly suppresses mouse in vitro decidualization. CONCLUSIONS: Our results indicated that CRH is strong expressed in primary decidua and should play a role during mouse decidualization. IMPLICATIONS: This result should shed lights on understanding the underlying mechanism during embryo implantation and decidualization.
Corrigendum to: Influence of neonatal estrogens on rat prostate development.
Prins GS, Birch L, Habermann H … +4 more , Chang WY, Tebeau C, Putz O, Bieberich C
Reprod Fertil Dev · 2026 Jul · PMID 42324846 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cellular and molecular characterization of the testicular development of GDF9-edited pigs.
Jiang T, Guo J, Jiao Y … +8 more , Xu M, He J, Liu X, Qin G, Liu X, Chen Y, Cong P, He Z
Reprod Fertil Dev · 2026 Jun · PMID 42309824 · Publisher ↗
CONTEXT: Growth differentiation factor (GDF) 9 is a member of the transforming growth factor (TGF)-β superfamily, which plays an important role in mammalian ovarian follicular development and female fertility. However, i...
CONTEXT: Growth differentiation factor (GDF) 9 is a member of the transforming growth factor (TGF)-β superfamily, which plays an important role in mammalian ovarian follicular development and female fertility. However, its regulatory role in the male reproductive system remains largely unknown. AIMS: This study aimed to investigate the regulatory mechanism of GDF9 in porcine testicular development. METHODS: We established a GDF9-edited pig model through CRISPR-Cas9 technology and somatic cell nuclear transplantation. The testicular development of one edited piglet at birth and one at Day 14 were characterized via Western blotting, haematoxylin-eosin staining, and immunohistochemistry at cellular and molecular levels. KEY RESULTS: Based on the preliminary analysis of one edited piglet at birth and one at Day 14, we did not observe changes to the gross morphological and anatomical structures of porcine testes at early developmental stages. However, the developmental process or cellular functions of Sertoli cells, Leydig cells and spermatogonia may be affected, as reflected by the altered expression patterns of SOX9, AR, DHRS9, DDX4 and ANXA2 in the testes. Noticeably, the altered expression of StAR may indicate an impact of GDF9 editing on the steroid hormone synthesis functions of porcine Leydig cells. CONCLUSIONS: These findings indicate that GDF9 may affect porcine testicular development at the early postnatal stage. IMPLICATIONS: These preliminary results provide a valuable foundation for future comprehensive studies toelucidate the regulatory mechanism of GDF9 in porcine testicular development.
Comparative analysis of acidosis defense mechanisms in preimplantation embryos in BALB/c strain mice: in vivo vs in vitro development.
Isigibol Gezgin O, Akbulut MO, Erdogan S … +1 more , Erdogan S
Reprod Fertil Dev · 2026 May · PMID 42203519 · Publisher ↗
CONTEXT: Intracellular pH (pHi) regulation is critical for all cell types, including preimplantation embryos. Embryos maintain pHi homeostasis through ion exchangers that respond to both acidic and alkaline challenges. A...
CONTEXT: Intracellular pH (pHi) regulation is critical for all cell types, including preimplantation embryos. Embryos maintain pHi homeostasis through ion exchangers that respond to both acidic and alkaline challenges. AIMS: While alkalosis defense mechanisms decline in later embryonic stages, this study investigated whether acidosis defense mechanisms - specifically Na+/H+ exchanger (NHE) activity alone and in conjunction with sodium-dependent chloride/bicarbonate exchanger (NDBCE) - remain active across developmental stages in in vivo- and in vitro-derived embryos. METHODS: In vivo-derived embryos (from 2-cell to blastocyst stage) were collected from BALB/c strain female mice. To obtain embryos at the same stages under in vitro conditions, in vivo-derived pronuclear (PN) zygotes were incubated in potassium simplex optimized medium (KSOM) medium. All embryos were loaded with the pH-sensitive fluorophore BCECF-AM (2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester) and their recovery rates from induced acidosis were quantified microspectrofluorometrically in two different solutions (bicarbonate-free pHKFHM and pHKSOM). The contributions of NHE1 and NHE3 isoforms were assessed using specific inhibitors (cariporide and S3226). Additionally, indirect immunofluorescence was performed to visualize NHE and NDBCE proteins in a subset of embryos. KEY RESULTS: The exchanger activities were high at the 2-cell stage of the embryos and there was no significant decrease across in vivo or in vitro developmental stages. Both NHE1 and NHE3 isoforms contributed to acidosis recovery. CONCLUSIONS: We found that both in vitro and in vivo embryos returned to resting pH at comparable rates in both solutions. IMPLICATIONS: The absence of functional differences between in vivo- and in vitro-cultured embryos implies that advanced-stage in vitro-derived embryos retain physiological competence, supporting their potential use in IVF applications.
Formation of the hyaluronan-serum-derived hyaluronan-associated protein complex during cumulus expansion contributes to in vitro maturation of porcine oocytes.
Yokoo M, Kimura N
Reprod Fertil Dev · 2026 May · PMID 42134982 · Publisher ↗
CONTEXT: Serum-derived hyaluronan-associated proteins (SHAPs), which are identical to the heavy chains of the inter-α-trypsin inhibitor (ITI) family of proteins, bind to hyaluronan produced by cumulus cells, thus forming...
CONTEXT: Serum-derived hyaluronan-associated proteins (SHAPs), which are identical to the heavy chains of the inter-α-trypsin inhibitor (ITI) family of proteins, bind to hyaluronan produced by cumulus cells, thus forming the hyaluronan-SHAP complex, which stabilises the hyaluronan-rich matrix of cumulus-oocyte complexes (COCs) during cumulus expansion. However, the role of the hyaluronan-SHAP complex in inducing oocyte maturation is still poorly understood. AIMS: Hence, this study was conducted to investigate the effects of hyaluronan retention within COCs on the formation of the hyaluronan-SHAP complex during cumulus expansion in porcine oocytes matured in vitro. METHODS: Western blot analysis and enzyme-linked immunosorbent assays were performed to detect SHAPs in porcine follicular fluid (pFF) and to quantify hyaluronan respectively. KEY RESULTS: The degree of cumulus expansion and oocyte maturation rates were proportional to the amount of hyaluronan retained within the COCs. SHAP was detected in pFF used for in vitro oocyte maturation and in the matrix of expanded COCs. Furthermore, immunodepletion of the ITI family proteins from pFF not only inhibited the formation of the hyaluronan-rich COC matrix, but also decreased oocyte maturation rates in a concentration-dependent manner. CONCLUSIONS: These results suggest that hyaluronan-SHAP complex formation during cumulus expansion may contribute to oocyte maturation. IMPLICATIONS: This finding is important for improving the culture system for porcine oocyte maturation in vitro.
Impact of repeated ovulation induction and superovulation on ovarian reserve and early embryo development in obese and PCOS-like mouse models.
Kunhiraman JP, Dcunha R, Madhvacharya VV … +7 more , R VL, Venkatraman G, Shah NR, Kumar A, Adiga SK, Kannan N, Kalthur G
Reprod Fertil Dev · 2026 May · PMID 42128672 · Publisher ↗
CONTEXT: Women with obesity or polycystic ovary syndrome (PCOS) often require repeated ovulation induction (OI) due to ovulatory dysfunction and infertility. However, the cumulative effects of repeated stimulation on ova...
CONTEXT: Women with obesity or polycystic ovary syndrome (PCOS) often require repeated ovulation induction (OI) due to ovulatory dysfunction and infertility. However, the cumulative effects of repeated stimulation on ovarian function and embryo development remain poorly understood. AIMS: The present study aimed to understand the consequences of repeated OI and/or repeated superovulation (SO) on preimplantation embryonic development in obese (high-fat diet-induced) and PCOS (high-fat diet and dehydroepiandrosterone-induced) mouse models. METHODS: Control (without any metabolic disorder), obese, and PCOS mice were divided into three experimental groups. The mice in one round of superovulation (SO1) were injected with 5 IU intraperitoneal (i.p.) injection of pregnant mare serum gonadotropin, followed by 10 IU of human chorionic gonadotropin 48 h later. In the repeated superovulation (SO3) group, mice were subjected to three rounds of superovulation with a gap of 9 days between each superovulation. Mice in the OI3 + SO3 group were administered with three doses of CC (50 mg/kg body weight, i.p., gap of 9 days between each CC injection), followed by three rounds of superovulation. KEY RESULTS: Both single and three rounds of superovulation resulted in decrease in primordial follicles and a moderate increase in atretic follicles in obese and PCOS mice. Reduction in the number of ovulated oocytes, increased rate of abnormal fertilization, decrease in blastocyst rate and elevated DNA damage in blastocysts were observed in in vitro fertilization-derived embryos. CONCLUSIONS: These findings demonstrate compromised embryonic development following repeated ovarian stimulation. IMPLICATIONS: The study highlights need for mild ovarian stimulation strategies in metabolically compromised patients undergoing infertility treatments.
Dynamic of extracellular matrix remodeling and follicular morphology in cattle ovarian slices cultivated in medium supplemented with Croton argyrophyllus Kunth essential oil.
Félix EDS, Azevedo VAN, Silva FFD … +5 more , de Assis EIT, Martins SD, Araújo VR, Gomes GA, Silva JRV
Reprod Fertil Dev · 2026 May · PMID 42108167 · Publisher ↗
CONTEXT: Ovarian tissue culture is commonly associated with increased follicular degeneration and extracellular matrix (ECM) changes largely owing to oxidative stress. AIMS: To investigate whether culture medium suppleme...
CONTEXT: Ovarian tissue culture is commonly associated with increased follicular degeneration and extracellular matrix (ECM) changes largely owing to oxidative stress. AIMS: To investigate whether culture medium supplementation with Croton argyrophyllus Kunth essential oil (CAEO) attenuates the alterations in follicle morphology, integrity of ECM and stromal cells in cultured tissues. METHODS: Ovarian slices were cultivated for 6 days in α-MEM+ alone or with 0.01, 0.1, 1.0, 10.0, and 100.0 μg/mL CAEO. Subsequent to the culture period, the proportion of follicle survival and development were determined by histological analysis. The collagen and glycosaminoglycan areas, as well as the stromal cells numbers, were determined. KEY RESULTS: Ovarian tissue cultivated with 10.0 and 100.0 μg/mL CAEO showed higher percentage of normal follicles. Irrespective of the concentration, CAEO promoted an increase in collagen fiber density compared with tissues cultivated in α-MEM+ only, keeping the values similar to uncultured control. A reduction in collagen density was observed around primary follicles in comparison to primordial follicles in cultured tissues. The CAEO did not influence glycosaminoglycans, but the presence of 100.0 μg/mL CAEO increased the number of stromal cells compared with tissues cultured in control medium. CONCLUSIONS: The CAEO (10 and 100 μg/mL) increased follicle survival and improved collagen fiber organization in cultured ovarian slices. The stromal cell density was also increased in tissues cultured with 100.0 μg/mL CAEO. IMPLICATIONS: The CAEO is a promising supplement for improving in vitro ovarian tissue culture conditions.
FGF2, LIF, and IGF1 supplementation during in vitro maturation or culture improves equine ICSI embryo development in an age-dependent manner.
Smith JM, Palacios PD, Segura Forero PA … +4 more , Gurkin RJ, Doyle T, Boe-Hansen G, Gambini A
Reprod Fertil Dev · 2026 May · PMID 42091240 · Publisher ↗
CONTEXT: Ovum pickup (OPU) combined with intracytoplasmic sperm injection (ICSI) has reshaped equine assisted reproduction, enabling embryo production from mares and stallions with constrained breeding opportunities; how...
CONTEXT: Ovum pickup (OPU) combined with intracytoplasmic sperm injection (ICSI) has reshaped equine assisted reproduction, enabling embryo production from mares and stallions with constrained breeding opportunities; however, limited efficiency of in vitro maturation (IVM) and in vitro culture (IVC) continues to hinder embryo production. Growth factor supplementation with fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), and insulin-like growth factor 1 (IGF1) in combination (FLI) has been shown to enhance oocyte and embryo developmental competence in several species. AIMS: This study evaluated whether FLI supplementation during IVM or IVC improves developmental outcomes of equine ICSI embryos and whether responses are influenced by donor mare age. METHODS: Oocytes were assigned to IVM with or without FLI or cultured post-ICSI in IVC media with or without FLI. Developmental outcomes, including maturation, cleavage, blastocyst formation, blastocyst diameter, and pregnancy establishment, were assessed across defined donor-mare age categories. KEY RESULTS: FLI supplementation did not affect overall maturation or cleavage rates. Blastocyst formation was significantly increased only in oocytes from middle-aged mares when FLI was added during either IVM or IVC. Supplementation during IVC also increased blastocyst diameter. Pregnancy establishment to Day 45 was marginally higher for embryos derived from FLI-treated oocytes, particularly following vitrification. CONCLUSIONS: These findings showed age-dependent responses to FLI, with the greatest benefit in middle-aged mares, supporting further molecular studies of its developmental effects. IMPLICATIONS: These results indicated that FLI supplementation can be incorporated into equine OPU-ICSI systems to improve clinical embryo production outcomes, particularly for middle-aged donor mares.
Paeonol alleviates intrauterine adhesion by suppressing endometrial stromal cell activation via AKT1, based on network pharmacology.
Liu W, Shi W, Zheng J … +6 more , Du Y, Jiang Y, Zhao C, Zhang Z, Feng L, Huang X
Reprod Fertil Dev · 2026 May · PMID 42062178 · Publisher ↗
CONTEXT: Intrauterine adhesion (IUA) causes secondary infertility and recurrent miscarriage, yet therapeutic options remain limited. Paeonol is widely used for gynecological diseases, but its precise role in IUA therapy...
CONTEXT: Intrauterine adhesion (IUA) causes secondary infertility and recurrent miscarriage, yet therapeutic options remain limited. Paeonol is widely used for gynecological diseases, but its precise role in IUA therapy is unclear. AIMS: This study aims to explore the molecular mechanism of paeonol in IUA. METHODS: Network pharmacology identified paeonol's potential targets and core proteins via a protein-protein interaction network. Bioinformatic pathway enrichment analyses and molecular docking elucidated mechanisms and validated binding. The optimal concentration and treatment time of paeonol were screened using Cell Counting Kit-8 (CCK-8) assays. In a transforming growth factor (TGF)-β-induced activated primary endometrial stromal cell (ESC) model, paeonol's effects on proliferation and migration were evaluated using CCK-8, wound healing, and Transwell assays. Expression levels of AKT1 and collagen synthesis-related markers were assessed by Western blotting. Protein levels of type I collagen and vimentin were assessed by immunofluorescence staining. In a IUA rat model, the in vivo efficacy of paeonol in alleviating IUA via AKT1 regulation was validated based on pathological, inflammatory, and reproductive parameters. KEY RESULTS: Paeonol targets were significantly enriched in the phosphoinositide 3-kinaseK-AKT pathway. In vitro, paeonol blocked TGF-β-induced activation of primary ESC, reducing cell viability and migration. Mechanistically, paeonol antagonised TGF-β-induced ESC activation by suppressing AKT1, thereby attenuating IUA. In vivo, paeonol alleviated pathological changes of endometrial tissues, reduced fibrosis, and suppressed inflammation in IUA rats. CONCLUSION: Paeonol blocks AKT1 activation to suppress inflammation and fibrosis, ultimately slowing IUA progression. IMPLICATIONS: This study provides a new theoretical basis for paeonol use in IUA therapy.
Integrative analysis of follicular fluid metabolites, exosomal miRNAs and granulosa cell mRNAs shows their interplay in women of advanced maternal age.
Li Z, Wang S, Mao X … +6 more , Zhang X, Wei P, Chen L, Liu L, Xue L, Ruan Z
Reprod Fertil Dev · 2026 May · PMID 42036331 · Publisher ↗
CONTEXT: Advanced maternal age (especially over 40 years) shows markedly declined fertility, although the exact mechanisms remain unclear. Exosomal microRNAs (miRNAs) within follicular fluid (FF) regulate granulosa cell...
CONTEXT: Advanced maternal age (especially over 40 years) shows markedly declined fertility, although the exact mechanisms remain unclear. Exosomal microRNAs (miRNAs) within follicular fluid (FF) regulate granulosa cell (GC) functions, thereby inducing alterations in the metabolic features of the FF. However, the specific dysregulation and functional impact of this exosomal miRNA-GC axis in the context of ovarian aging require further elucidation. AIMS: To delineate the distinct expression profiles of FF exosomal miRNAs and GC mRNAs, coupled with FF metabolic features, in women of advanced maternal age, and to explore the integrated regulatory networks linking these components. METHODS: FF samples were collected from the aged group (≥40 years, n = 19) and young group (≤30 years, n = 19). Centrifugation separated it into GCs, exosomes, and the remaining FF containing metabolites. Each fraction was analyzed for differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differential metabolites (DMs). KEY RESULTS: Analysis identified 373 DEmRNAs, 50 exosomal DEmiRNAs (targeting 2633 genes), and 97 DMs. Integrated correlation analysis pinpointed a core regulatory axis, hsa-miR-132-3p_CHAC1, which was strongly associated with four key metabolites (7-HOCA, Lysopc(18:1), 9(S)-Hpode, Androsterone Sulfate). This axis potentially disrupts cellular redox homeostasis. CONCLUSIONS: Multiomics analysis uncovered a dysregulated FF exosomal miRNA_GC mRNA_metabolite network in women of advanced maternal age compared with the young group, with the hsa-miR-132-3p_CHAC1 axis potentially mediating age-related ovarian dysfunction via perturbed cellular redox homeostasis. IMPLICATIONS: This study offers insights into the mechanisms underlying the age-related decline in female fertility.
Regulation of YAP1 during oocyte maturation.
Sun T, Diaz FJ
Reprod Fertil Dev · 2026 May · PMID 42009945 · Publisher ↗
CONTEXT: Yes-associated protein 1 (YAP1) plays essential roles in somatic cell proliferation and differentiation and is regulated by cell cycle proteins and mechanical cues transduced by the actin cytoskeleton. YAP1 has...
CONTEXT: Yes-associated protein 1 (YAP1) plays essential roles in somatic cell proliferation and differentiation and is regulated by cell cycle proteins and mechanical cues transduced by the actin cytoskeleton. YAP1 has been localized to the mitotic spindle. Whether YAP1 may participate in oocyte maturation is not known. AIMS: Determine effect of YAP inhibitor on oocyte maturation and the potential involvement of cell cycle regulators and actin polymerization modulators on YAP localization and phosphorylation status during oocyte maturation. METHODS: Mouse oocytes were cultured in vitro alone or in the presence of various small molecule inhibitors blocking YAP1, cyclin dependent kinase 1 (CDK1), phosphatase protein 2 A (PP2A), actin polymerization and the resulting effects on maturation, YAP localization by immunocytochemistry and/or YAP phosphorylation by western blot were determined. KEY RESULTS: Blocking YAP1 activity with verteporfin hampers oocyte maturation, arresting the majority of oocytes at metaphase I (MI), with a distorted spindle structure. Moreover, YAP1 localized to the meiotic spindle and is phosphorylated on T119 beginning at metaphase I, which is regulated in part by PP2A phosphatase but is not strongly affected by CDK1 inhibitors (RO-3306). The increase in YAP1 phosphorylated on T119 (pYAP1) at MI mirrors the rise in CDK1 activity, suggesting an association between CDK1, pYAP1-T119 and PP2A. CONCLUSIONS: The results link pYAP1-T119 with cell cycle regulators CDK1, PP2A, and the meiotic spindle, but not with changes in actin polymerization. These findings suggest a previously unknown role of YAP1 in regulating meiotic spindle shape during oocyte maturation. IMPLICATIONS: Modulation of YAP1 activity during oocyte maturation may allow for better in vitro maturation procedures to be developed.
Your field needs your data! Raising the standard of quality control and data accessibility in reproductive proteomics.
Skerrett-Byrne DA
Reprod Fertil Dev · 2026 May · PMID 42002535 · Publisher ↗
The field needs your data. Despite rapid progress in reproductive proteomics, a major barrier to scientific advancement remains the limited availability and transparency of proteomic datasets. Although more than 2000 spe...
The field needs your data. Despite rapid progress in reproductive proteomics, a major barrier to scientific advancement remains the limited availability and transparency of proteomic datasets. Although more than 2000 sperm proteomics studies are indexed on PubMed, fewer than 414 datasets have been deposited in ProteomeXchange, leaving the majority of published findings effectively inaccessible for reanalysis. This Viewpoint highlights the urgent need for improved data stewardship, standardised quality control and open access to raw mass spectrometry files across reproductive biology. In this article, I outline how transparent false discovery rate control, true biological replication and clearly defined quantitative thresholds are essential for generating robust and interpretable proteomic outputs. I further discuss how interactive data platforms, such as ShinyApps, can substantially improve the accessibility and usability of these complex reproductive proteomic datasets. Using recent examples, I demonstrate how public data reanalysis can uncover species-conserved pathways, improve proteome coverage, validate biological functions and enable new discoveries and insights far beyond the aims of the original studies. Finally, I present a practical roadmap for authors, reviewers and journals to ensure that reproductive proteomics embraces the FAIR data principles, and moves towards a culture where sharing raw data, comprehensive metadata and interactive applications becomes standard practice. To support implementation, a concise checklist is provided to summarise key criteria for data availability, quality control and metadata reporting. Improving data accessibility and quality will not only strengthen individual studies, but will accelerate discovery and create a more robust, connected and future-proof foundation for reproductive biology.
Synergistic effect of glutathione and metformin mitigates testicular apoptosis by ameliorating gonadotropin hormones and gene expression in streptozotocin-induced diabetic male mice.
Sardar R, Abdullah F, Kamsani YS … +1 more , Khan NMN
Reprod Fertil Dev · 2026 Apr · PMID 41968057 · Publisher ↗
CONTEXT: Diabetes mellitus (DM) is a metabolic disorder that impairs the body's ability to regulate blood sugar levels, leading to cellular damage and apoptosis. Metformin (Met) and glutathione (GSH) are key antioxidants...
CONTEXT: Diabetes mellitus (DM) is a metabolic disorder that impairs the body's ability to regulate blood sugar levels, leading to cellular damage and apoptosis. Metformin (Met) and glutathione (GSH) are key antioxidants that prevent damage to mitochondrial DNA and proteins by modulating oxidative stress in testicular cells. AIMS: This study assessed concomitant therapy with GSH and Met to mitigate testicular apoptosis in diabetic male mice. METHODS: Six- to eight-week-old male BALB/c mice were randomly divided into four groups (n = 6): DM control, DM + Met (200 mg/kg), DM + GSH (15 mg/kg), and DM + Met (200 mg/kg) + GSH (15 mg/kg). Diabetes was induced by i.p. injection of 50 mg/kg body weight (BW) streptozotocin for five consecutive days. The DM control group served as a baseline to evaluate the effects of treatments. GSH was administered weekly (i.p.), and Met was administered orally daily for 35 consecutive days. KEY RESULTS: BW and fasting blood glucose levels were monitored on Day 0 and Day 44. The fasting blood glucose levels were reduced (P < 0.05, P < 0.01, P < 0.001) while BW, the number of Bax-positive cells, Bax mRNA expression, and Bax : Bcl-2 ratio were restored in all treatment groups (P < 0.05, P < 0.01, P < 0.001). In contrast, FSH, LH, testosterone, the number of Bcl-2 positive cells, Bcl-2 mRNA expression, and mitochondrial genes were increased in all treatment groups (P < 0.05, P < 0.01, P < 0.001). CONCLUSION: These findings suggest that GSH combined with Met restores apoptotic and mitochondrial dynamics, potentially mitigating diabetes-associated testicular damage by modulating the expression of genes involved in apoptotic and mitochondrial processes, thus positioning GSH as a promising complementary therapy. IMPLICATIONS: Combined GSH and Met therapy may offer a novel synergistic strategy to protect male fertility in diabetes condition by targeting cellular stress pathways. Further studies are warranted to translate these findings into clinical applications.
IL10 is a potent modulator of IL1-mediated inflammation in bovine endometrial explants.
Meyerholz-Wohllebe MM, Kneidl AM, Knoch ST … +6 more , Haug S, Weber F, Zablotski Y, Gabler C, Petzl W, Zerbe H
Reprod Fertil Dev · 2026 Apr · PMID 41942315 · Publisher ↗
CONTEXT: Bovine uterine inflammation impairs fertility, animal welfare and economics. Balanced regulation of interleukin-1 family proteins is crucial to resolve endometrial inflammation. AIM: mRNA expression of interleuk...
CONTEXT: Bovine uterine inflammation impairs fertility, animal welfare and economics. Balanced regulation of interleukin-1 family proteins is crucial to resolve endometrial inflammation. AIM: mRNA expression of interleukin 1B (IL1B) and its receptor antagonist (IL1RA) was examined in bovine endometrial explants. METHODS: Endometrial explants from 26 cows were incubated with heat-inactivated pathogenic Escherichia coli, opportunistic Bacillus pumilus or commensal and potentially protective Lactobacillus buchneri (3, 14 and 24 h) and with cytokines (24 h; IL1B, IL17A, IL10). mRNA expression of IL1B and IL1RA was quantified via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and mixed effects models were used for statistical analysis. KEY RESULTS: IL1B mRNA expression increased after bacterial challenge at all timepoints (P < 0.001). IL1RA mRNA expression increased after Escherichia coli and Bacillus pumilus exposure only at 3 h, but after Lactobacillus buchneri at 14 and 24 h (P < 0.010). A pro-inflammatory shift of the IL1RA:IL1B ratio was detected at all timepoints and for all bacterial challenges (P < 0.020). Stimulation with IL10 reduced IL1B and IL1RA mRNA expression and shifted the IL1RA:IL1B ratio in an anti-inflammatory direction (P < 0.001). CONCLUSION: This study confirmed explant culture as a suitable model for analyzing inflammatory regulation in the bovine endometrium and identified IL10 as a potent modulator of endometrial IL1B and IL1RA. IMPLICATIONS: Not only Escherichia coli and Bacillus pumilus, but also unexpectedly Lactobacillus buchneri, induced initial pro-inflammatory mRNA expression patterns to be different depending on culture duration. This highlights the need for further research on pathogenic and opportunistic versus potentially protective bacteria in bovine uterine health.
Harnessing reproductive biology to conserve wildlife species.
Martin LL, Fanson KV, Johnston SD … +13 more , Lewis PJ, Meachem SJ, O'Leary PD, Parrott ML, Pask AJ, Pavlova A, Richings NM, Rivers N, Sumner J, Temple-Smith P, Tubbs CW, Wong BBM, Rodgers RJ
Reprod Fertil Dev · 2026 Apr · PMID 41922081 · Publisher ↗
Habitat destruction, changing climate and other anthropogenic impacts have resulted in the recorded extinctions of hundreds of species, with many more undocumented extinctions being likely to have occurred. Approaches to...
Habitat destruction, changing climate and other anthropogenic impacts have resulted in the recorded extinctions of hundreds of species, with many more undocumented extinctions being likely to have occurred. Approaches to conserving threatened species include protection or improvement of habitat, fenced conservation reserves, species translocations and reintroductions, elimination of environmental toxins, breeding programs in reserves or captivity, and genetic rescue and management. The latter includes storage of gametes, stem cells or embryos, to both conserve species and maintain or expand their genetic diversity. Many of these approaches require a basic knowledge of the reproductive biology of the species of interest. Such knowledge is difficult to achieve because of the astonishing diversity of species-specific reproductive strategies that have evolved. Unfortunately, for many species we simply do not have that knowledge. This report summarises key discussions from a workshop titled Reproductive Biology Research Needed for Saving our Wildlife held in Melbourne, Australia, and attended by stakeholders from zoos, wildlife organisations, universities, museums and government organisations. The workshop prioritised aspects of reproductive biology knowledge needed, how this knowledge might be obtained, and how it should be deployed. Using examples of planned and successful conservation strategies for individual species, the workshop participants considered environmental challenges, managing introduced species, captive breeding programs, challenges for assisted reproductive technologies, de-extinction science in conservation efforts, examination of reproductive steroid hormones across species, endocrine disruption, and cryopreservation of genomic diversity to assist the management of wild and captive populations. The workshop highlighted the magnitude of the issues involved and identified reproductive approaches to be used to direct future conservation efforts for saving threatened species.
A concept-enhanced, knowledge graph-guided framework for interpretable PCOS prediction: a case study in explainable biomedical artificial intelligence.
Kulshrestha S, Kumar N, Verma P … +5 more , Sikri K, Gangwar M, Sengupta A, Aggarwal S, Narad P
Reprod Fertil Dev · 2026 Mar · PMID 41887676 · Publisher ↗
CONTEXT: Overcoming the disconnect between efficient Machine Learning (ML) techniques and its therapeutic applicability necessitates frameworks that provide clear, contextualized evidence. AIMS: The present work examines...
CONTEXT: Overcoming the disconnect between efficient Machine Learning (ML) techniques and its therapeutic applicability necessitates frameworks that provide clear, contextualized evidence. AIMS: The present work examines the efficacy of a conceptually-enhanced framework that combines biological domain expertise, knowledge graphs, and probabilistic inference with ML predictions. We employed this innovative strategy for predicting polycystic ovary syndrome (PCOS). METHODS: PCOS clinical data (541 patients) was sourced from Kaggle. Clinically relevant conceptual characteristics were developed and integrated with raw data using a knowledge graph (KG) employing TransE-based semantic proximity scoring and a Bayesian network (BN) to characterize conditional dependencies. Knowledge-driven concepts were included in subsequent ML procedures, including LazyPredict for model screening, and ensemble model construction from top 10 models based on accuracy using soft-voting ensemble classifier. Patient-specific, guideline-compliant explanations were designed to accompany all model predictions for improved interpretability. KEY RESULTS: The approach demonstrated robust predictive abilities, with the concept-integrated ensemble model demonstrating the strongest performance, with a five-fold stratified cross-validation accuracy of 93.65% (95% CI: 91.59-95.63%) and a ROC-AUC of 0.98 (95% CI: 0.96-1.00%). In addition to predicting accurately, the incorporation of features obtained from KG and BN significantly improved interpretability, with causal probabilities based on BN proving to be the most important feature. The framework facilitated patient-specific, concept-based interpretations consistent with clinical guidelines. CONCLUSION: The integration of biomedically-relevant concepts improves the interpretability of PCOS predictions while maintaining predictive performance. IMPLICATIONS: Our work proposes the use of clinician-aligned PCOS screening tools that provide transparent risk classification and informed treatment decisions.
Are antioxidants hindering stallion sperm capacitation? A perspective on hidden barriers to equine IVF success.
Medica AJ, Gibb Z, Ortiz-Rodriguez JM … +1 more , Swegen A
Reprod Fertil Dev · 2026 Mar · PMID 41819494 · Publisher ↗
Heavy use of antioxidants in equine in vitro fertilisation (IVF) media may suppress the reactive oxygen species (ROS) signals stallion sperm need for capacitation, which depends on high mitochondrial activity and a well-...
Heavy use of antioxidants in equine in vitro fertilisation (IVF) media may suppress the reactive oxygen species (ROS) signals stallion sperm need for capacitation, which depends on high mitochondrial activity and a well-maintained endogenous redox homeostasis. A species-specific approach balancing oxidative protection with controlled ROS signalling could improve fertilisation efficiency and reduce prolonged incubation times.
Single-oocyte mRNA sequencing reveals that AMH-overexpression alters oocyte gene expression.
Hore TA, Pankhurst MW
Reprod Fertil Dev · 2026 Mar · PMID 41668467 · Publisher ↗
CONTEXT: Anti-Müllerian hormone (AMH) regulates ovarian follicle development, but AMH overexpression has been linked to impaired fertility and pregnancy failure. Our previous studies indicated that AMH overexpression hin...
CONTEXT: Anti-Müllerian hormone (AMH) regulates ovarian follicle development, but AMH overexpression has been linked to impaired fertility and pregnancy failure. Our previous studies indicated that AMH overexpression hindered preimplantation embryo development. AIMS: To investigate whether AMH influences oocyte competence, we performed single-oocyte RNA sequencing from wild-type (Thy1.2-AMH0/0) and AMH-overexpressing (Thy1.2-AMHTg/0) mice. METHODS: Individual, naturally-ovulated mouse oocytes underwent denuding, followed by preparation of cDNA libraries for sequencing. Thy1.2-AMH0/0 and AMH-overexpressing Thy1.2-AMHTg/0 oocytes were compared by principle component, differential gene expression and gene ontology analyses. KEY RESULTS: Principal component analysis revealed that global transcriptomic variation was greater within groups than between groups; however, differential expression analysis identified 39 significantly altered transcripts. The most prominent changes included increased expression of Rps3a3 (70-fold), Hormad1 (22-fold), and Fnip2 (5.6-fold), alongside reduced expression of the ribosomal gene Rps3a. Gene ontology enrichment highlighted mitochondrial function and DNA repair pathways. Our findings suggest that sustained AMH signalling during late folliculogenesis modifies oocyte gene expression. CONCLUSIONS: Subtle differences exist between the gene expression profiles of oocytes that develop in an environment with slightly increased AMH levels. IMPLICATIONS: Increased AMH expression may be detrimental to oocyte development.
'Vanishing twin syndrome' following frozen embryo transfer has no detrimental effects on offspring growth and development up to 3 years.
Yu C, Ge J, Chen Y … +8 more , Xia X, Wang X, Zhou J, Wang S, Shen D, Chen Y, Hu L, Lu R
Reprod Fertil Dev · 2026 Apr · PMID 41663129 · Publisher ↗
CONTEXT: Vanishing twin syndrome (VTS) is a common condition in assisted reproductive procedures, where a multi-fetus pregnancy is spontaneously reduced to a singleton pregnancy. However, the effects of VTS on the develo...
CONTEXT: Vanishing twin syndrome (VTS) is a common condition in assisted reproductive procedures, where a multi-fetus pregnancy is spontaneously reduced to a singleton pregnancy. However, the effects of VTS on the development of the remaining fetus is relatively unknown. AIMS: The purpose of this study was to estimate the effect of VTS on the dynamic measurement of growth and development of the singletons (0-3 years) born from frozen embryo transfer (FET). METHODS: This study was a retrospective cohort design and was carried out from January 2017 to December 2023. To optimize statistical efficiency and reduce confounding variables, singletons conceived using VTS were matched at a 4:1 ratio based on the couples' ages, body mass index, occupation, women's anti-Müllerian hormone (AMH) levels, and embryo status. Ultimately, 66 children in the VTS group and 264 children in the non-VTS group were included in the final analysis. KEY RESULTS: After propensity matching, there was no significant difference in growth and development of children between the VTS group and the non-VTS group. The number of embryos transferred in the VTS group were higher than the non-VTS group (P < 0.0001). The height and the head circumference (at 3 months) in the VTS group were lower than the non-VTS group (P < 0.05). CONCLUSIONS: The occurrence of VTS did not detrimentally affect the growth and development of offspring (0-3 years) from FET. IMPLICATIONS: More comprehensive and long-term follow-up results are needed for further verification. More than one embryo transfer not only increases the rate of multiple births, but also increases the occurrence of VTS in assisted reproductive technologies (ART).
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