Reproduction, Fertility, And Development[JOURNAL]
Sun
200 papers
Collection: Non-photoperiodic actions of melatonin.
Abecia JA, Martin G
Reprod Fertil Dev · 2026 Feb · PMID 41630536 · Publisher ↗
Blurb: This collection in Reproduction, Fertility and Development addresses a developing area of melatonin biology. Historically, melatonin has been seen as a pineal hormone that plays one essential role - the synchronis...
Blurb: This collection in Reproduction, Fertility and Development addresses a developing area of melatonin biology. Historically, melatonin has been seen as a pineal hormone that plays one essential role - the synchronisation of reproductive and other brain-controlled functions with changes in photoperiod. Often driven by the detection of melatonin receptors in non-brain tissues, it has become clear that melatonin plays a much wider variety of roles in the function of the testis, sperm, ovary, follicles, oocyte, embryo, placenta, fetus, and mammary gland. This collection presents this broader view of melatonin biology, and how the new concepts can be applied to livestock production.
FAM216A and CCDC166 are not essential for male fertility.
Hou S, Wei X, Zhang Y … +14 more , Yang C, Gao Y, Xiao Y, Ju Z, Jiang Q, Wang J, Wang Y, Zhao W, Liu W, Li Y, Gao Y, Wang Z, Wang X, Huang J
Reprod Fertil Dev · 2026 Mar · PMID 41630526 · Publisher ↗
CONTEXT: Bull fertility is crucial for livestock reproductive efficiency, yet studies on bull spermatozoa and its molecular mechanisms remain limited. Direct research in cattle is challenging, while gene-knockout mouse m...
CONTEXT: Bull fertility is crucial for livestock reproductive efficiency, yet studies on bull spermatozoa and its molecular mechanisms remain limited. Direct research in cattle is challenging, while gene-knockout mouse models provide an effective alternative for investigating gene functions. AIMS: This study aimed to investigate the role of two testis-enriched genes, FAM216A and CCDC166, in male fertility. METHODS: We evaluated the conservation of FAM216A and CCDC166 in mammals through phylogenetic analysis and sequence alignment. Their expression patterns were investigated using published single-cell transcriptome data and RT-PCR. The role of these genes in reproductive function was assessed through knockout mouse models, histochemical staining, and fertility analysis. KEY RESULTS: FAM216A and CCDC166 are highly conserved across mammalian species and abundantly expressed in testicular tissues. Knocking out these two genes does not affect male fertility in mice. CONCLUSIONS: Knockout of Fam216a and Ccdc166 did not impair male fertility in mice, suggesting functional redundancy. Under the experimental conditions applied, they do not appear to be key factors for male fertility, and similar outcomes may be expected in bulls. IMPLICATIONS: Although Fam216a and Ccdc166 are not essential for male fertility in mice, this study provides critical guidance for future research. It facilitates more targeted investigations of other candidate genes and avoids unnecessary studies, while also laying a foundation for exploring their functions in other physiological processes and diseases.
Visfatin as a modulator of factors involved in human placental invasion and angiogenesis: interactions with folic acid and aspirin.
Dawid M, Milewicz T, Rak A
Reprod Fertil Dev · 2026 Mar · PMID 41604509 · Publisher ↗
CONTEXT: Our previous studies demonstrated the expression of visfatin in the human placenta and its impact on placental cell proliferation and apoptosis. AIMS: This study aimed to examine the effect of visfatin, folic ac...
CONTEXT: Our previous studies demonstrated the expression of visfatin in the human placenta and its impact on placental cell proliferation and apoptosis. AIMS: This study aimed to examine the effect of visfatin, folic acid (FA), and aspirin (ASA) on markers of invasion and angiogenesis in the human placenta. METHODS: JEG-3 cells and placental villi from normal pregnancies at term were treated for 48 h with visfatin (1 ng/mL, 10 ng/mL or 100 ng/mL) to assess the levels of metalloproteinases (MMP-2/MMP-9), their inhibitors (TIMP-1/TIMP-2), and vascular endothelial growth factors (VEGFA/PLGF). Next, using a pharmacological inhibitor of both the insulin receptor (INSR) and selected kinase pathways, the action of visfatin on the levels of MMPs, TIMPs, VEGFA, and PLGF was analyzed in JEG-3 cells. Finally, using the same research model, the effects of FA (2 nM, 20 nM, 100 nM) or ASA (0.1 mM) on visfatin and INSR expression, as well as the levels of the mentioned factors regulating invasion and angiogenesis, were studied. KEY RESULTS: Visfatin increased MMP-9 levels, while decreasing MMP-2, TIMPs, VEGFA, and PLGF, through distinct intracellular pathways. FA reduced visfatin level and modulated INSR, while ASA decreased both. Moreover, the combined use of FA or ASA with visfatin altered the effect observed for visfatin alone. CONCLUSIONS: Visfatin acts as a novel regulator of invasion factors and decreases the levels of agents involved in angiogenesis. Folic acid or aspirin can modulate its activity. IMPLICATIONS: The regulatory potential of FA and ASA on visfatin action may be relevant in the context of pregnancy-related pathologies.
The effect of seminal plasma on the mass motility of epididymal ram spermatozoa.
Van de Hoek M, Rickard JP, de Graaf SP
Reprod Fertil Dev · 2026 Mar · PMID 41587296 · Publisher ↗
CONTEXT: Mass motility assessment is widely used to evaluate semen quality in the sheep breeding industry, yet the biological factors influencing motility duration remain poorly characterised. At ejaculation, spermatozoa...
CONTEXT: Mass motility assessment is widely used to evaluate semen quality in the sheep breeding industry, yet the biological factors influencing motility duration remain poorly characterised. At ejaculation, spermatozoa are combined with seminal plasma (SP), which initially supports motility and function but may compromise long-term metabolic endurance. AIMS: This study aimed to investigate the effects of SP on mass motility duration and pH regulation of epididymal ram spermatozoa. METHODS: Epididymal sperm were incubated with whole SP, saline, or left undiluted to assess motility duration. Subsequently, sperm were incubated with varying SP concentrations and molecular weight-separated fractions (protein-free <3 kDa; protein-enriched >3 kDa) and assessed for motility and pH over 24 h. Metabolomic and lipidomic profiling via targeted mass spectrometry characterised the biochemical composition of each SP fraction. KEY RESULTS: SP exposure significantly reduced mass motility duration (195 ± 11 min) compared with undiluted sperm (1797 ± 185 min; P = 0.0123) and saline dilution (2667 ± 134 min; P < 0.0001). All SP-treated groups exhibited a progressive pH decline, consistent with increased glycolytic flux, whereas SP-naïve sperm showed stable or increasing pH, indicating a more regulated metabolic state and greater metabolic flexibility. The protein-free SP fraction was most detrimental to motility, which was likely to be the result of the depletion of key proteins, lipids, and metabolites associated with energy production. CONCLUSIONS: Prolonged exposure to SP impairs ram sperm motility longevity by promoting a glycolysis-biased metabolic state and reducing metabolic endurance. IMPLICATIONS: Understanding how seminal plasma composition influences sperm metabolic regulation may inform strategies to better preserve sperm motility during semen handling and storage.
Corrigendum to: Data-driven biomarker discovery and risk profiling for polycystic ovary syndrome in Indian women using ensemble learning.
Verma P, Agarwal R, Sharma LK … +1 more , Sindwani N
Reprod Fertil Dev · 2026 Jan · PMID 41520683 · Publisher ↗
Abstract loading — click title to view on PubMed.
SOD1 and SOD2 gene variants are significantly correlated with male infertility in a North Indian population, suggesting a possible pleiotropic conflict.
Bhan S, Bhagat M, Sopori S … +4 more , Sharma B, Kumar R, Dhar A, Bhat A
Reprod Fertil Dev · 2026 Feb · PMID 41518663 · Publisher ↗
CONTEXT: Oxidative stress has a detrimental effect on sperm quality, which can lead to infertility. Antioxidant enzymes, such as superoxide dismutases (SODs), have crucial role to protect sperms from oxidative stress. Va...
CONTEXT: Oxidative stress has a detrimental effect on sperm quality, which can lead to infertility. Antioxidant enzymes, such as superoxide dismutases (SODs), have crucial role to protect sperms from oxidative stress. Variations in the SOD genes have thus been linked to male fertility. AIMS: The primary aim of the study was to evaluate the genetic factors contributing to male reproductive health in the population of Jammu and Kashmir. Specifically, the study aimed to assess the impact of SOD1/rs4998557 and SOD2/rs4880 polymorphisms on risk of male infertility and to investigate the gene-gene interactions between SOD1 and SOD2 variants to determine their combined effect on susceptibility to male infertility. METHODS: SOD1/rs4998557 and SOD2/rs4880 single nucleotide variants (SNVs) were genotyped in 411 males (208 cases and 203 controls) using TaqMan probe and quantitative polymerase chain reaction (qPCR) technique to investigate the role of these polymorphisms in male infertility in the North Indian population of Jammu and Kashmir. KEY RESULTS: Logistic regression analysis using SPSS showed a significant correlation of both SNVs with male infertility in the study population. The SOD2/rs4880C>T (Ala16Val) variant showed a significant positive correlation [OR = 2.02 (95% CI:1.27-3.20), adjusted P = 0.003] and SOD1/rs4998557G>A intronic variant a significant negative correlation [OR = 0.43 (95% CI:0.27-0.69), adj. P = 0.001] with male infertility. The gene-gene interaction analysis suggested that the concomitant presence of SOD2/rs4880 and SOD1/rs4998557 effectively reduces the risk for infertility. CONCLUSIONS: Our data indicated a pleiotropic conflict between SOD2/rs4880 and SOD1/rs4998557 in male infertility. Specifically, SOD2/rs4880 is linked to an increased risk of male infertility, whereas SOD1/rs4998557 is associated with a decreased risk. To the best of our knowledge, this is the first study to report the association of SOD SNVs with male infertility in any Indian population. IMPLICATIONS: As the first study to report these associations in an Indian population, it highlights the importance of regional genetic diversity. This paves the way for more inclusive, ethinicity based genetic counselling and reproductive medicine in South Asia. Additionally, the discovery that one variant increases risk while the other decreases risk suggests that male infertility is governed by complex balance of oxidative defence mechanisms.
Investigation of endocannabinoid 2-AG and its hydrolases for regulation on sperm motility and acrosome reaction in Kunming mice.
Zhang X, Wu W, Li Y … +1 more , Yang M
Reprod Fertil Dev · 2026 Feb · PMID 41518662 · Publisher ↗
CONTEXT: A key endocannabinoid, 2-arachidonoyl glycerol (2-AG), regulates sperm hyperactivation in humans via alpha/beta hydrolase domain-containing protein 2 (ABHD2)-mediated CatSper calcium channel activation. However,...
CONTEXT: A key endocannabinoid, 2-arachidonoyl glycerol (2-AG), regulates sperm hyperactivation in humans via alpha/beta hydrolase domain-containing protein 2 (ABHD2)-mediated CatSper calcium channel activation. However, the role of ABHD2 in mice is unclear, whereas monoacylglycerol lipase (MAGL), ABHD-containing protein 6 (ABHD6), and ABHD-containing protein 12 (ABHD12) modulate 2-AG in the mouse central nervous system (CNS). AIMS: This study explored the impact of 2-AG on mouse sperm motility, its regulatory mechanisms, and the involvement of MAGL, ABHD6, and ABHD12. METHODS: 2-AG concentrations in caput and caudal epididymal sperm from Kunming mice were quantified. ABHD2/6/12 and MAGL were identified, localized, and assessed for roles in motility and calcium (Ca2+) influx. KEY RESULTS: Caput sperm exhibited higher 2-AG contents than did caudal sperm. Four hydrolases regulated motility via 2-AG hydrolysis to induce calcium influx. MAGL showed the strongest hydrolytic activity, ABHD2 the weakest. Subcellular localization showed MAGL in mid-piece, ABHD12 in mid-piece and principal piece, and ABHD2/ABHD6 in acrosomal region. CONCLUSIONS: 2-AG modulates mouse sperm motility via calcium signaling. MAGL, ABHD6, and ABHD12 drive 2-AG hydrolysis, while ABHD2 is linked to acrosome exocytosis, not 2-AG breakdown. IMPLICATIONS: Targeting MAGL/ABHD12 offers non-hormonal contraceptive strategies or assisted reproductive technology (ART) improvements. Monitoring 2-AG and hydrolase activity could aid in diagnosing male infertility.
Is intracytoplasmic sperm injection (ICSI) the solution when there is not any problem; exploring ICSI vs in vitro fertilization (IVF) outcomes in sibling oocytes from donor sperm assisted reproductive technology (ART) cycles.
Golbary Kinory E, Kalma Y, Lavie S … +3 more , Barda S, Azem F, Fuchs Weizman N
Reprod Fertil Dev · 2026 Feb · PMID 41518661 · Publisher ↗
CONTEXT: Intracytoplasmic sperm injection (ICSI) is increasingly used in assisted reproductive technology (ART), even in cases without male factor infertility. Its true benefit in such scenarios remains uncertain. AIMS:...
CONTEXT: Intracytoplasmic sperm injection (ICSI) is increasingly used in assisted reproductive technology (ART), even in cases without male factor infertility. Its true benefit in such scenarios remains uncertain. AIMS: To determine whether ICSI provides any embryological or clinical advantage over conventional in vitro fertilization (IVF) in cycles without male factor infertility, using donor sperm and sibling oocytes. METHODS: This retrospective cohort study included 52 women treated at Lis Maternity and Women's Hospital (2018-2024). Each patient underwent split-cycle fertilization with both ICSI and IVF using donor sperm, with sibling oocytes serving as internal controls. Embryological outcomes (fertilization, morphology, Gardner grading, morphokinetics) and clinical outcomes (fresh and frozen embryo transfers, cumulative pregnancy rates) were compared. Cycles in which embryos from both methods were transferred were excluded. KEY RESULTS: ICSI achieved a higher fertilization rate than did IVF (87.5%, 45.05%); however, no significant differences were observed in embryo quality on the basis of morphology and Gardner criteria. Morphokinetic analysis showed higher Day 3 cleavage grading in ICSI embryos (79.80% vs 71.43% IVF), but these advantages did not translate into improved pregnancy outcomes, such as clinical pregnancy rates (33.33% ICSI, 18.6% IVF). CONCLUSION: Among women without known infertility factors undergoing ART with donor sperm, ICSI did not confer clinical advantages over conventional IVF, despite higher fertilization rates. IMPLICATIONS: Given the higher cost, invasiveness, and frequent overuse of ICSI, its application should be reserved for cases with clear indications.
Lysine succinylation: a review of its impacts on the reproductive function and related disease.
Huang X, Huang Y, Lai J … +5 more , Wang Z, Ge C, Luo T, Cui Y, Li J
Reprod Fertil Dev · 2026 Feb · PMID 41490882 · Publisher ↗
Lysine succinylation is a recently identified post-translational modification of proteins that has been demonstrated to play critical roles in various biological activities. In recent years, research on succinylation has...
Lysine succinylation is a recently identified post-translational modification of proteins that has been demonstrated to play critical roles in various biological activities. In recent years, research on succinylation has progressed considerably in the context of reproductive biology and associated diseases, underscoring the importance of a comprehensive review on this topic. A key mechanism underlying succinylation involves changes in the activity of succinyltransferases and desuccinylases, which in turn regulate alterations in the succinylation level of target proteins, and thereby influence multiple cellular functions. Current studies have indicated that cellular succinylation levels are closely associated with both normal reproductive functions and related pathologies. For instance, elevated succinylation has been linked to impaired ovarian endocrine activity and the progression of cancers such as breast and ovarian cancer. The male reproductive system is involved in regulating spermatogenesis and has been associated with conditions including prostate and testicular cancer. Furthermore, diminished succinylation has been shown to disrupt the replacement of transition proteins in elongating spermatids and alter the distribution of germ cells within seminiferous tubules, indicating its essential role in male reproductive health. This review aims to provide a systematic overview of the fundamental characteristics of lysine succinylation and to elucidate its diverse functions within various aspects of the reproductive system, integrating recent advances to present a balanced perspective on both the physiological and pathological significance.
Comparison of the establishment of rat intrauterine adhesion models utilizing the double-injury method at different periods.
Yan Y, Wang F, Qiao M … +3 more , Li Q, Zhao W, Chen Y
Reprod Fertil Dev · 2026 Feb · PMID 41485235 · Publisher ↗
CONTEXT: A suitable animal model of intrauterine adhesion (IUA) is crucial for further investigating its pathological mechanisms and exploring effective therapeutic strategies. AIMS: This study compared the efficacy of e...
CONTEXT: A suitable animal model of intrauterine adhesion (IUA) is crucial for further investigating its pathological mechanisms and exploring effective therapeutic strategies. AIMS: This study compared the efficacy of establishing IUA animal models in non-pregnant rats at stages of estrous cycles versus pregnant rats using the dual-injury method, aiming to identify a model that better reflects the clinical pathogenesis of IUA. METHODS: Sprague Dawley female rats were randomly divided into control group (estrous phase, non-estrous phase) and model group (estrous phase, non-estrous phase and pregnancy phase). A dual-injury method was used to establish the IUA model. Fourteen days after modeling, the rat uterus was collected to assess the modeling effect by analyzing the number of endometrial glands and the degree of fibrosis and by detecting the expression levels of transforming growth factor-beta 1 (TGF-β1), interleukin 6 (IL-6), and integrin ανβ3 proteins. KEY RESULTS: Histological and molecular analyses were performed on the uterine tissues of each group. The results demonstrated that the dual-injury method effectively establishes an IUA animal model. The pregnancy model group had fewer glands and a larger area of fibrosis compared to the estrous and non-estrous model groups (P < 0.05). The pregnancy model group had higher expression levels of TGF-β1, IL-6 proteins and a lower expression level of integrin ανβ3 protein than did the estrous and non-estrous model groups (P < 0.05). CONCLUSION: Modeling during pregnancy yielded superior outcomes compared with modeling at stages of estrous cycles in non-pregnant rats. IMPLICATIONS: These findings have provided valuable insights for future researchers in selecting appropriate animal models to further elucidate the pathogenesis of clinical IUA.
ALB, GPX5 and PTGDS as potential biomarkers for the aging processes of the dog epididymis.
Cichowska-Likszo AW, Likszo P, Fraser L … +2 more , Mlynarz P, Mogielnicka-Brzozowska M
Reprod Fertil Dev · 2026 Jan · PMID 41433920 · Publisher ↗
CONTEXT: Alterations in the reproductive tract related to aging processes are reflected by changes in biochemical components such as proteins. AIMS: This study aimed (1) to investigate changes in canine epididymal fluid...
CONTEXT: Alterations in the reproductive tract related to aging processes are reflected by changes in biochemical components such as proteins. AIMS: This study aimed (1) to investigate changes in canine epididymal fluid protein abundance in relation to age, and (2) to select potential protein markers of canine reproductive tract aging. METHODS: Twenty-three mixed-breed dogs were used in the study. The dogs were divided into the following three experimental groups: ExG1 (1-3 years old); ExG2 (3.5-6 years old); and ExG3 (6.5-11 years old). Cauda epididymal fluid was collected from dissected tissues and centrifuged to separate the epididymal fluid from the epididymal sperm. Chromatography coupled with mass spectrometry (nanoUPLC-Q-TOF/MS) was used to analyze the proteins in the epididymal fluid. KEY RESULTS: The proteomic profiling uncovered 121, 122, and 56 unique proteins in ExG1, ExG2, and ExG3 respectively, with 48 proteins being common across all groups. Gene ontology analysis showed similar main molecular functions for all three ExGs; however, the percentage of particular proteins in each ExG differed. There were three proteins that showed significant (P < 0.05) changes in relative abundance among the ExGs, including albumin (ALB), epididymal secretory glutathione peroxidase (GPX5), and prostaglandin-H2 D-isomerase (PTGDS). CONCLUSIONS: The findings suggest that aging in dogs may influence epididymal fluid protein composition, particularly affecting ALB, GPX5, and PTGDS, which could play roles in oxidative and ion metabolic regulation. IMPLICATIONS: These findings suggest that ALB, GPX5, and PTGDS may serve as biomarkers for epididymal aging. Their detection could enhance the evaluation of epididymal semen quality, aiding reproductive medicine practices in dogs of different ages.
Advancements in sperm selection and assessment: traditional to cutting-edge methods in assisted reproductive techniques - a narrative review.
Staśczak A, Losa W, Student S … +2 more , Bułdak R, Horák S
Reprod Fertil Dev · 2026 Mar · PMID 41406322 · Publisher ↗
Infertility affects approximately 15% of couples globally, with male factors contributing to 20-70% of cases. These issues often stem from low sperm concentration, abnormal morphology, or poor motility, highlighting the...
Infertility affects approximately 15% of couples globally, with male factors contributing to 20-70% of cases. These issues often stem from low sperm concentration, abnormal morphology, or poor motility, highlighting the critical importance of sperm selection in both natural and assisted reproduction. The quality of selected spermatozoa impacts not only fertilization success but also the health of future offspring. Despite the advances in in vitro fertilization, no universally accepted method exists for selecting and assessing spermatozoa based on morphology, motility, and DNA quality. Over the past decade, significant progress has been made in sperm selection technologies, aimed at enhancing fertilization efficiency. Traditional methods are now complemented by innovative technologies like microfluidics and artificial intelligence, enabling more precise sperm data analysis. These tools improve the identification of the most fertile spermatozoa while reducing the risk of reproductive failures. Additionally, advancements in mathematical and computational modeling have enhanced our ability to simulate and predict sperm selection processes. These models incorporate crucial factors, offering deeper insights into sperm quality and behavior. This review discusses the current methods and devices used for sperm selection and assessment, recent trends in modeling these processes, and potential future directions. By analyzing the latest scientific literature, we explore how emerging technologies impact the effectiveness of sperm selection. These advancements hold promise for improving reproductive outcomes and developing innovative clinical and biotechnological tools.
In vivo and in vitro effects of GnRH antagonist treatment on steroidogenesis and folliculogenesis in the ovary of cyclic mice.
Singh P, Srivastava RK, Krishna A
Reprod Fertil Dev · 2026 Jan · PMID 41399204 · Publisher ↗
CONTEXT: Gonadotropin-releasing hormone antagonists (GnRH-Anta) can modulate reproductive hormonal activity without inducing the initial surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) typically...
CONTEXT: Gonadotropin-releasing hormone antagonists (GnRH-Anta) can modulate reproductive hormonal activity without inducing the initial surge in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) typically associated with GnRH agonists. Despite growing interest, the effects of GnRH antagonists on ovarian function, particularly under varying physiological conditions, remain inadequately understood. AIMS: This study aimed to evaluate the effects of different doses of GnRH-Anta on morphological and physiological changes in the ovaries of cyclic mice, both in vivo and in vitro. METHODS: Cyclic female mice were administered various doses of GnRH-Anta for eight consecutive days. To assess direct effects, ovaries collected from proestrus-stage mice were cultured with different concentrations of GnRH-Anta for 24 h at 37°C. KEY RESULTS: The administration of GnRH-Anta for eight consecutive days exhibited dose-dependent inhibitory effects on follicular development and luteinization, with a reduced number of growing follicles. This was accompanied by reduced circulating concentrations of progesterone and estradiol, subnormal luteal morphology, and a dose-dependent decline in the ovarian expression of 3β-hydroxysteroid dehydrogenase (3β-HSD), steroid receptors. An increase in atretic follicles observed was closely associated with elevated expression of apoptotic markers. The in vitro study showed inhibitory effect on the ovary even in the presence of LH. CONCLUSIONS: GnRH-Anta treatment affects various aspects of ovarian physiology, including follicular development, apoptosis, and steroidogenesis, in a dose- and context-dependent manner, influenced by the mode of treatment and the presence or absence of LH. IMPLICATIONS: GnRH-Anta may be used to suppress the release of LH and FSH, preventing premature ovulation and helping manage various reproductive conditions.
Medicago sativa alleviates behavioral impairments and oxidative stress in the cerebrum and cerebellum of ovariectomized mice.
Ghorbel Koubaa F, Jdidi H, Chaâbane M … +2 more , Aoiadni N, El Feki A
Reprod Fertil Dev · 2026 Jan · PMID 41399203 · Publisher ↗
BACKGROUND: Estrogen deficiency after menopause is linked to increased oxidative stress and cognitive impairment. Medicago sativa is known for its antioxidant properties, suggesting potential benefits in mitigating these...
BACKGROUND: Estrogen deficiency after menopause is linked to increased oxidative stress and cognitive impairment. Medicago sativa is known for its antioxidant properties, suggesting potential benefits in mitigating these effects. AIMS: This study aimed to evaluate the impact of Medicago sativa on behavior and oxidative stress parameters in the cerebrum and cerebellum of ovariectomized mice. METHODS: Female Swiss mice were divided into two sham-operated groups: the negative control mice (C) and Medicago sativa treated mice (MS), and three ovariectomized groups: ovariectomized mice (OVX) and ovariectomized mice treated either with 17β-estradiol (OVX-E) or with Medicago sativa (OVX-MS). Open field and radial eight-arm maze (RAM) tests were conducted to evaluate a general locomotor activity and memory of mice. Biochemical analyses were performed to measure oxidative stress markers and acetylcholinesterase activity in cerebrum and cerebellum. KEY RESULTS: In the OVX group, we observed a decrease in locomotor performance during the open field test and a progressive deterioration in spatial memory during the RAM test. An increase in lipid peroxidation, protein carbonyl and advanced oxidation protein product levels as well as a marked inhibition in the activities of antioxidant enzymes in cerebrum and cerebellum indicated the occurrence of oxidative stress after ovariectomy. Elevated acetylcholinesterase activity and histopathological changes in cerebrum and cerebellum were also observed in these mice. However, co-treatment of OVX mice with Medicago sativa resulted in an appreciable improvement of these parameters. CONCLUSION: Medicago sativa demonstrated protective effects against oxidative stress and cognitive deficits induced by estrogen deficiency. IMPLICATIONS: These findings suggest that Medicago sativa may serve as a promising therapeutic option for alleviating postmenopausal complications associated with estradiol deficiency.
Efficacy of glyoxal acid-free (GAF®) as a non-toxic fixative for fish gonads, gametes and larvae: widespread implications for laboratory studies, field sampling and applied aquaculture.
Locatello L, Fonsatti E, Detillo P … +7 more , Borgheresi O, Guidi L, Grassi E, Bortoletti M, Radaelli G, Pascoli F, Bertotto D
Reprod Fertil Dev · 2026 Jan · PMID 41397790 · Publisher ↗
CONTEXT: Traditional fixatives such as buffered formaldehyde (BF) and paraformaldehyde (PFA) are widely used but raise health concerns because of their toxicity. Their use is increasingly subject to regulatory restrictio...
CONTEXT: Traditional fixatives such as buffered formaldehyde (BF) and paraformaldehyde (PFA) are widely used but raise health concerns because of their toxicity. Their use is increasingly subject to regulatory restrictions, calling for the development of non-toxic alternatives. Glyoxal acid-free (GAF®) has emerged as a potential substitute. AIMS: This study evaluated GAF® for preserving gonadal tissues, oocyte, sperm, and larvae of the European seabass (Dicentrarchus labrax). METHODS: GAF formulations - standard and an optimized, marine-adapted formulation - were compared to conventional fixatives or fresh samples. KEY RESULTS: The standard GAF® led to tissue shrinkage and poor gamete preservation, whereas the optimized version effectively preserved oocyte, sperm, gonadal tissue, and delicate larval structures. Although 10% formalin still outperformed GAF® for certain larval tissues, extended fixation in optimized GAF® improved results. CONCLUSIONS: Overall, optimized GAF® represents a promising non-toxic alternative for histological applications in marine fish, although further refinement is needed for certain tissues and for the use in the oocyte cytoplasmic clarification applied in aquaculture broodstock selection. IMPLICATIONS: Non-toxic fixatives are fundamental to ensure operator safety, and identifying solutions that effectively preserve samples is essential; therefore, studies such as this one have important implications for both field and laboratory settings.
Evaluating sperm-polymorphonuclear leukocyte interactions in vitro: the immunomodulatory role of seminal plasma and implications for future ovine studies.
Mikhael L, Warr S, de Graaf SP … +1 more , Rickard JP
Reprod Fertil Dev · 2026 Jan · PMID 41385721 · Publisher ↗
The complex anatomical, biochemical and immunological architecture of the ovine cervix presents a substantial barrier to frozen-thawed (FT) ram spermatozoa migration following cervical artificial insemination (AI). A key...
The complex anatomical, biochemical and immunological architecture of the ovine cervix presents a substantial barrier to frozen-thawed (FT) ram spermatozoa migration following cervical artificial insemination (AI). A key component of the immunological barriers involves interactions between FT sperm and polymorphonuclear neutrophils (PMN), which are known to infiltrate the female reproductive tract (FRT) following semen deposition and engage in effector mechanisms, specifically degranulation, release of neutrophil extracellular traps (NETs) and phagocytosis. Seminal plasma (SP) has been shown to play a critical immunomodulatory role in regulating sperm-PMN interactions across several species, including sheep, reducing sperm-PMN binding in vitro. During in vitro processing and cryopreservation, SP is inherently diluted, potentially exacerbating immune-mediated clearance of FT sperm. Identifying the specific components of SP responsible for this immunoprotective effect may inform targeted supplementation strategies. Extracellular vesicles (EVs), a heterogenous class of SP-containing proteins, lipids, metabolites and nucleic acids, are also emerging as key mediators of immunological communication. Their potential role in modulating sperm-PMN interactions warrants further investigation to help understand sperm-PMN interactions and implications for improving survival of FT ram sperm in the cervix following AI.
Post-transcriptional regulatory mechanisms of dosage compensation in vertebrates.
Lister NC, McIntyre KL, Waters PD
Reprod Fertil Dev · 2025 Dec · PMID 41339281 · Publisher ↗
Sex chromosome dosage compensation is thought to be essential in species with heteromorphic sex chromosomes. There has been a large emphasis on transcriptional regulation as the primary mechanism restoring gene dosage ba...
Sex chromosome dosage compensation is thought to be essential in species with heteromorphic sex chromosomes. There has been a large emphasis on transcriptional regulation as the primary mechanism restoring gene dosage balance. However, emerging evidence across vertebrate lineages indicates that post-transcriptional mechanisms make critical contributions to balancing X/Z gene dosage in the proteome. Here, we propose potential mechanisms that may be responsible for this post-transcriptional regulation, including nonsense mediated decay (NMD), N6-methyladenosine RNA methylation (m6A) and sex specific micro-RNAs (miRNAs). We propose that multi-layered regulation of sex chromosome dosage is an ancient and widespread strategy. Recognizing the role of post-transcriptional processes not only reframes current models of dosage compensation, but also uncovers novel mechanisms underpinning development, reproduction and disease.
Optimized protocols of meiotic arrest maintenance improved in vitro maturation of ovine oocytes.
He N, Wang YQ, Jiang L … +8 more , Bai TH, Wang MM, Zhang M, Xu JL, Gong S, Yuan HJ, Tan JH, Luo MJ
Reprod Fertil Dev · 2025 Dec · PMID 41292062 · Publisher ↗
CONTEXT: The developmental potential (DP) of in vitro-matured (IVM) oocytes is considerably lower than that of in vivo-matured oocytes, primarily owing to the premature resumption of meiosis without adequate cytoplasmic...
CONTEXT: The developmental potential (DP) of in vitro-matured (IVM) oocytes is considerably lower than that of in vivo-matured oocytes, primarily owing to the premature resumption of meiosis without adequate cytoplasmic maturation during IVM. Evidence indicates that meiotic arrest maintenance (MAM) during IVM significantly enhances oocyte DP. However, studies on ovine oocytes remain scarce. AIMS: To optimize MAM protocols for improving maturation of ovine oocytes. METHODS: Ovine oocytes collected from abattoir-derived ovaries were subjected to MAM culture for 24 h, followed by assessment of MAM efficiency and oocyte DP. KEY RESULTS: When used individually, roscovitine (RSC), db-cAMP, and U0126 showed suboptimal MAM efficiency. However, their combined application at substantially reduced concentrations yielded markedly improved outcomes. A combination of 12.5 μM RSC, 1000 μM db-cAMP, and 10 μM U0126 achieved high MAM efficiency, and when MAM lasted for 18 h, it resulted in significantly higher oocyte DP than in control oocytes matured without MAM. Furthermore, oxidative stress was detected during MAM, and the addition of antioxidants during the 24 h MAM period enhanced oocyte DP beyond that of non-MAM controls. CONCLUSIONS: High MAM efficiency and improved oocyte DP were achieved using a combination of RSC, db-cAMP, and U0126 at reduced concentrations, indicating that meiotic arrest in ovine oocytes is regulated through multiple signaling pathways. Antioxidant supplementation is essential for successful extended MAM. IMPLICATIONS: Findings are critical for refining MAM and IVM protocols and for advancing understanding of mechanisms governing oocyte meiotic arrest and maturation.
Synchronized breeding and reproductive resilience in dairy cattle: mitigating metritis, heat stress, and transgenerational fertility impairment.
Lima FS
Reprod Fertil Dev · 2026 Jan · PMID 41292035 · Publisher ↗
Heat stress profoundly compromises reproductive efficiency in dairy cattle by disrupting follicular and oocyte development, altering steroid hormone profiles, impairing estrous expression and ovulation, reducing fertiliz...
Heat stress profoundly compromises reproductive efficiency in dairy cattle by disrupting follicular and oocyte development, altering steroid hormone profiles, impairing estrous expression and ovulation, reducing fertilization success, hindering embryonic development, and increasing early embryonic loss. Although the molecular mechanisms underlying these disruptions remain incompletely understood, significant advances in reproductive technologies have been developed to mitigate the negative impact of heat stress on reproductive performance. Estrous cycle synchronization programs, enabling timed artificial insemination (AI), emerged in the mid-1990s and reduced heat stress-related reproductive inefficiencies by eliminating the need for estrus detection, improving submission rates, and optimizing the ovulation-to-insemination interval, thereby enhancing pregnancy rates per AI. Embryo transfer (ET) has been adopted as a complementary strategy to bypass fertilization failure during hot periods, whereas genetic selection, most notably the introgression of the SLICK-1 allele of the prolactin receptor gene (PRLR), confers thermotolerance via a sleek hair coat and improved heat dissipation. Nevertheless, heat stress also exacerbates common postpartum disorders such as metritis, which negatively affect fertility regardless of AI, ET, or thermotolerant genotypes, underscoring the importance of preventive herd-health management. Furthermore, exposure to heat stress during fetal development imposes transgenerational consequences, diminishing the health, productivity, longevity, and fertility of subsequent generations. This review evaluates current and emerging technologies, including timed AI, ET, genetic selection for thermotolerance and reproductive resilience, and preventive approaches to postpartum disease, while also addressing strategies to mitigate the transgenerational impairments induced by heat stress in dairy cattle.
From reservoir to rendezvous: the journey of sperm through the oviduct.
Miller DJ
Reprod Fertil Dev · 2026 Jan · PMID 41292027 · Full text
Once viewed simply as a pipeline connecting the ovary and uterus where fertilization and early development occur, the oviduct is becoming more appreciated for its complex functions. The utero-tubal junction (UTJ) restric...
Once viewed simply as a pipeline connecting the ovary and uterus where fertilization and early development occur, the oviduct is becoming more appreciated for its complex functions. The utero-tubal junction (UTJ) restricts the entry of sperm to those meeting specific morphological and molecular requirements. Once sperm passes the UTJ, the isthmus functions as a storage reservoir, retaining sperm before fertilization and prolonging their lifespan, allowing for more asynchrony between sperm deposition and ovulation. Some mammals, such as bats, store sperm for months, but a few days of storage is more common among most species. In the isthmus, some sperm adhere to the oviduct epithelium whereas others are free and moving. Some of the adherent sperm detach from oviduct cells and move to the ampulla, relying on a complex interplay that brings a limited number of sperm to rendezvous with oocytes. Thus, the oviduct is responsible for sperm selection, storage, transport, maturation, and fertilization. Focused primarily on mammals, this review discusses the mechanisms underpinning each of these steps.
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