Female Reproduction Research Articles

The Response of the Gut Physiological Function and Microbiome of a Wild Freshwater Fish (Megalobrama terminalis) to Alterations in Reproductive Behavior.

The fish gut microbiome is well known for its role in degrading nutrients to improve the host's digestion and absorption efficiency. In this study, we focused on the core physiological adaptability during the various reproductive stages of the black Amur bream (Megalobrama terminalis) to explore the interaction mechanisms among the fish host gut mucosal structure, gut enzyme activity, and gut microbial metabolism in the course of the host's reproductive cycle. Our findings showed that M. terminalis exhibited locomotion metabolic type (aids in sporting) in the reproductive stage, and a change to visceral metabolic type (aids in digestion) during non-reproductive and post-reproductive stage phases. The impact of metabolic type selection and energy demand during various reproductive stages on fish nutrition strategy and digestive function was substantial. Our resulted showed that mitochondria in intestinal epithelial cells of reproductive M. terminalis appeared autophagy phenomenon, and the digestive enzyme activities in the intestines of reproductive M. terminalis were lower than those in the non-reproductive and post-reproductive individuals. Moreover, these differences in nutrition strategy have a prominent impact on the gut microbiome of reproductive M. terminalis, compared to non-reproductive and post-reproductive samples. Our findings showed that reproductive females had lower levels of alpha diversity compared to non-reproductive and post-reproductive females. Our results also showed a greater functional variety and an increase in functional genes related to carbohydrate, lipid, amino acid, cofactors, and vitamin metabolic pathways in the NRS and PRS group. It is noteworthy that an enrichment of genes encoding putative enzymes implicated in the metabolism of taurine and hypotaurine was observed in the RS samples. Our findings illustrated that the stability and resilience of the gut bacterial community could be shaped in the wild fish host-microbiome interactions during reproductive life history.

CRISPR/Cas9-mediated Nap knockout affects female reproduction and egg shape in Bombyx mori.

Insect reproductive capacity can affect effective pest control and infertility studies and has become an important focus in recent molecular genetic research. Nucleosome assembly protein (Nap) is highly conserved across multiple species and is involved in forming the sperm nucleus in many species. We used clustered regularly interspaced palindromic repeats/Cas9 technology to knockout BmNap in Bombyx mori and observed that the mutations caused female infertility, whereas male fertility was not affected. BmNap mutants grew and mated normally; however, female mutants laid smaller eggs that could not be fertilised and did not hatch. In addition, female sterility produced by the mutation could be inherited stably via male mutants; therefore, Nap could be used as a potential target for lepidopteran pest control through population regulation. In the current study, we elucidated a new function of BmNap, increased the understanding of the oogenesis regulation network in Lepidoptera and promoted the development of insect sterility technologies.

O-037 An update on the genetics of dizygotic twinning

Abstract Study question Which genes are involved in female fertility defined as giving birth to naturally conceived dizygotic (DZ) twins? Summary answer In 2016 we identified FSHB and SMAD3 as first loci for having DZ twins. We now report four additional loci: GNRH1, FSHR, ZFPM1 and IPO8. What is known already The propensity to give birth to DZ twins differs around the globe, is positively associated with body size and smoking, and runs in families. Heritability estimates tend to be low. Study design, size, duration We conducted a genome-wide association meta-analysis (GWAMA) of mothers of naturally conceived dizygotic (DZ) twins (8,265 cases, 264,567 controls) and of independent DZ twin offspring (26,252 cases, 417,433 controls). Participants were carefully screened to exclude twins born after use of Medically Assisted Reproduction (MAR) technologies. Participants/materials, setting, methods Over 700.000 participants from Australia, New Zealand, Europe and USA were included. Genetic association analyses by cohort for being a mother of DZ twins and being a DZ twin were combined by fixed-effects inverse variance methods as implemented in METAL software meta-analysis. To predict the most likely effector gene in a locus, we applied the new FLAMES framework which integrates machine learning with biological data linking SNPs to genes, and GWAS-wide convergence of gene interactions. Main results and the role of chance By enlarging sample size from previous efforts, both by including new cohorts and by combining through meta-analyses with independent DZ offspring, we identified 4 genome-wide significant loci, in addition to FSHB (follicle stimulating hormone subunit beta ) and SMAD3 (SMAD family member 3). Two novel loci GNRH1 (gonadotropin releasing hormone 1) and FSHR (follicle stimulating hormone receptor) have well-established roles in female reproduction. The 2 further novel genes were implicated by gene level enrichment analyses. Both ZFPM1 (Zinc Finger Protein, FOG Family Member 1) and IPO8 (Importin 8) have not previously been implicated. Significant genetic correlations were found with multiple aspects of female reproduction and body size as well as with a recent GWAMA of female infertility. The 26 top SNPs from our GWAMA in European-origin participants predicted the crude twinning rates in 47 non-European populations (r = 0.23 between risk score and population prevalence, p=.058) indicating that GWAS are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. A Phenome-wide association study (PheWAS) based on the GWAMA, linked SNPs predisposing to DZT with reduced risk of both ovarian dysfunction and polycystic ovaries. Limitations, reasons for caution So far, our studies only included European ancestry cohorts. Inclusion of data from Africa (the highest world-wide DZ twining rates are observed in Western Africa) and Asia (lowest DZ twinning rate) will further illuminate the etiology of twinning and female fertility. Wider implications of the findings About one in 40 babies born in the world is a twin and there is still much unknown why they run in families. We hope our results will inform investigations of female fertility and infertility. Trial registration number not applicable

P-708 melatonin alleviates circadian rhythm disruption-induced enhanced luteinizing hormone pulsatility and ovarian dysfunction in vivo and in vitro

Abstract Study question Is melatonin deficiency a reversible cause of abnormal pattern of luteinizing hormone (LH) pulsatility and ovarian dysfunction caused by circadian rhythm disruption (CRD)? Summary answer Melatonin could rescue the augmented LH pulsatility and reproductive abnormalities caused by CRD. What is known already Melatonin, mainly synthesized and released by pineal gland, engages in regulating circadian rhythms. When circadian rhythms are disrupted, the nocturnal productions of melatonin are suppressed. Evidence suggests that circadian rhythm disruption (CRD) is associated with reproductive dysfunctions, while melatonin plays a vital role for female reproduction as a free radical scavenger and a neuroendocrine regulator. The gonadotrophin-releasing hormone (GnRH) drives pulsatile luteinizing hormone (LH) secretion, which is also essential for fertility. Study design, size, duration We used 90 CBA/CaJ mice to establish the chronic jet-lag model in which mice were exposed to an 8 hr time shift every 3 days. After 8 weeks of jet-lag induction, some of the mice were given melatonin treatment for 4 weeks. Furthermore, we used a perfusion system in vitro to mimic the process of CRD-induce high-frequency GnRH pulses stimulation of LβT2 gonadotrope cells. Participants/materials, setting, methods Repetitive tail-tip blood collection was used to evaluate the pattern of LH pulsatility. Blood plasma samples were collected from 4 mice at 4-hour intervals to measure levels of melatonin. Follicular development was evaluated by ovarian histology. Reproductive hormones was detected by ELISA. Immunohistochemistry and western blot were used to detect the expression of melatonin receptor 1A (MT1). The LβT2 cells were exposed to pulsatile GnRH at high pulse frequencies to mimic augmented pulsatile GnRH stimulation. Main results and the role of chance CRD mice exhibited reproductive-endocrine dysfunction, including irregular estrous cycles, reduced number of corpus lutea (CL), and decreased levels of estradiol and progesterone. Additionally, CRD enhanced the frequency and amplitude of LH pulsatility and pituitary LH beta-subunit expression. Melatonin administration alleviated these CRD-induced reproductive abnormalities and reversed the augmented LH pulsatility. The expression of MT1 decreased in the anterior pituitaries of CRD mice but increased after melatonin treatment, indicating the essential role of MT1 in melatonin’s reversal of CRD-induced enhanced LH pulsatility. Limitations, reasons for caution Further research is needed to validate the applicability and safety of these findings in humans. Wider implications of the findings The results suggest that melatonin may be a beneficial option for patients with reproductive-endocrine abnormalities, particularly those with circadian rhythm disruption. Trial registration number 82101719

Extended lifespan in female Drosophila melanogaster through late-life calorie restriction

Calorie restriction has many beneficial effects on healthspan and lifespan in a variety of species. However, how late in life application of caloric restriction can extend fly life is not clear. Here we show that late-life calorie restriction increases lifespan in female Drosophila melanogaster aged on a high-calorie diet. This shift results in rapid decrease in mortality rate and extends fly lifespan. In contrast, shifting female flies from a low- to a high-calorie diet leads to a rapid increase in mortality and shorter lifespan. These changes are mediated by immediate metabolic and physiological adaptations. One of such adaptation is rapid adjustment in egg production, with flies directing excess energy towards egg production when shifted to a high diet, or away from reproduction in females shifted to low-caloric diet. However, lifelong female fecundity reveals no associated fitness cost due to CR when flies are shifted to a high-calorie diet. In view of high conservation of the beneficial effects of CR on physiology and lifespan in a wide variety of organisms, including humans, our findings could provide valuable insight into CR applications that could provide health benefits later in life.

Early detection of pregnancy status in cattle using ISG17 polyclonal antibody recombinant

Abstract Optimization of female cattle reproduction requires reliable and accurate systems for early pregnancy detection. Identifying pregnant status as early as possible is essential in managing reproductive cycles because it allows farmers to make early decisions about rebreeding strategies. Interferon stimulated gen (ISG) 17 is a gene expressed during maternal recognition pregnancy through Interferon tau (IFN-T) secretion signal, which begins on days 8 to 9 of pregnancy and peaks on days 16 to 17 (day 0 = day of estrus). This study aims to detect ISG17 expression using ISG17 polyclonal antibodies as a determinant of pregnancy in cattle that have received artificial insemination. The polyclonal antibody of ISG17 was produced in New Zealand white rabbits using ISG17 recombinant protein expressed by pET-32b expression vector in Escherichia coli systems of strain pLys BL21-Origami. ISG17 polyclonal antibody (ISG17-pAb) was used to detect ISG17 proteins expressed in blood serum obtained from 2 to 10 weeks-inseminated cattle (Frisian Holstein and Ongole) by NCM-ELISA method. ISG17-pAb was also labeled with gold nanoparticles and assembled into a lateral flow system for easier pregnancy detection in the field. NCM-ELISA test results showed a typical reaction between ISG17 antigen and ISG17-pAb in the form of brown dots after adding DAB substrate. Detection of pregnancy status showed that the antibody reaction to blood serum from dairy cows indicated 13.2% false negatives, 15.8% false positives, and 71.0% accuracy. In comparison, blood serum from beef cattle showed 7.5% false negatives, 0% false positives, and 92.5% accuracy. Interestingly, a lateral flow kit based on ISG17-pAb-gold nanoparticles showed good antibody reactions against blood serum from pregnant and non-pregnant cows. This indicates that the development of early pregnancy detection based on ISG17-pAb is prospective for optimizing productive cows by continuing to increase accuracy.

Immunohistochemical Changes of Polycystic Ovaries in rats Treated with Asparagus Officinalis L. Roots Extract

Abstract Background: Polycystic ovary syndrome (PCOS) which a series reproductive, metabolic and psychological condition that is characterized by abnormal gonadotropin secretion or hyperandrogenism and associated with insulin resistance and most commonly found in the reproductive age female. Objectives: This research paper were conducted to examine the effects of Asparagus officinalis L. roots extract on letrozole induced PCOS where the effect of 400 mg/kg A. officinalis L. root extract on the PCOS was studied for 28 days in female rats. Materials and Methods: Thirty-five female Albino rats were randomly divided into five groups, including control negative group, positive control, PCOS, treatment and preventive group. During 28 days, the positive control group got an extract of the A. officinalis roots. Letrozole 1 mg/kg dissolve in 0.5% carboxymethyl cellulose solution was used to cause PCOS for 28 days. Following the induction of PCOS, the treatment group received extract A. officinalis roots for 28 days. The preventative group received an extract of asparagus roots during PCOS induction. Results: Immunohistochemical results are shown Ovary slices from of the therapeutic and preventative groups next to the asparagus group were immunostained for Ki 67, which showed high positive statistically (P <0.05) immunological activity in the granulosa nuclei and less in the theca cells. When compared to the PCOS group, both the granulosa and theca layers had very weak positive immunostaining (P <0.05). According to the morphological findings, granulosa cells from the Control group and asparagus group proliferated much more than granulosa cells from the PCOS group statistically significant (P <0.05). Conclusion: The findings show that theca and granulosa cells are quickly stimulated to proliferate by asparagus root extract. Moreover, it therefore speeds up oogenesis and early cell divisions.

Loss of Function of Vasoactive-intestinal Peptide Alters Sex Ratio and Reduces Male Reproductive Fitness in Zebrafish.

Vasoactive-intestinal peptide (Vip) is a pleiotropic peptide with a wide range of distribution and functions. Zebrafish possess 2 isoforms of Vip (a and b), in which Vipa is most homologous to the mammalian form. In female zebrafish, Vipa can stimulate LH secretion from the pituitary but is not essential for female reproduction, as vipa-/- females display normal reproduction. In contrast, we have found that vipa-/- males are severely subfertile and sex ratio of offspring is female-biased. By analyzing all aspects of male reproduction with wild-type (WT) males, we show that the testes of vipa-/- are underdeveloped and contain ∼70% less spermatids compared to WT counterparts. The sperm of vipa-/- males displayed reduced potency in terms of fertilization (by ∼80%) and motility span and duration (by ∼50%). In addition, vipa-/- male attraction to WT females was largely nonexistent, indicating decreased sexual motivation. We show that vipa mRNA and protein is present in Leydig cells and in developing germ cells in the testis of WT, raising the possibility that endogenous Vipa contributes to testicular function. Absence of Vipa in vipa-/- males resulted in downregulation of 3 key genes in the androgen synthesis chain in the testis, 3β-hsd, 17β-hsd1, and cyp11c1 (11β-hydrogenase), associated with a pronounced decrease in 11-ketotestosterone production and, in turn, compromised reproductive fitness. Altogether, this study establishes a crucial role for Vipa in the regulation of male reproduction in zebrafish, like in mammals, with the exception that Vipa is also expressed in zebrafish testis.

Modeling the economic performance of small ruminant pastoralist flocks and financial impact of changes in reproductive performance and mortalities in Kajiado county, Kenya

This study investigated the economic performance of pastoralist small ruminant flocks in Kajiado county, Kenya, and the financial impact of mortalities and changes in performance indicators. A survey of 129 pastoralist small ruminant flocks captured production and economic data for a 12-month period via interview. Simulation models were then developed for flocks with different performance levels and trading activities. Their gross margins, and the financial impact from mortalities, were estimated. Sensitivity analyses were conducted for select performance indicators to assess their relative economic importance. On average, pastoralists who were not purchasing supplementary feed (79% of flocks) had gross margins of KSh 3,016 – KSh 3,123 per reproductive female. Goat production generated 2.43–2.51 times greater returns than sheep production. High efficiency mixed flocks achieved 2.04–2.06 times greater returns than medium efficiency flocks, and 12.19–14.25 times greater returns than low efficiency flocks. Pastoralist-only flocks had 3.82–4.01 times greater returns than pastoralist-traders. Financial losses due to mortality were on average 17.81% of the starting flock value. Fecundity and abortion rates in sheep, and parturition rate in goats, had the greatest economic impact. The developed models could support decision-making toward improving the economic performance of pastoralist flocks and the evaluation of interventions and external shocks.

Assessing the health-fitness dynamics of endangered mountain caribou and the influence of maternal penning

The health of wildlife plays a crucial role in population demography by connecting habitat and physiology. Southern mountain caribou, a population of woodland caribou ( Rangifer tarandus caribou (Gmelin, 1978)) found in the mountains of southwest Canada, are facing significant threats. We evaluated the health of the Klinse-Za subpopulation within the central group of southern mountain caribou, which is part of an Indigenous-led conservation initiative aimed at enhancing caribou population growth through seasonal maternal penning. We collected health metrics from 46 female Klinse-Za caribou between 2014 and 2021. The health metrics included trace minerals, cortisol, biomarkers for inflammation, and pathogen prevalence. We compared these health metrics between penned and non-penned animals, reproductive and non-reproductive females, and nearby subpopulations. We provide correlative evidence linking reproductive success to trace nutrients but find no evidence for relationships with stress, exposure to pathogens, or biomarkers of inflammation. Based on the health metrics considered, Klinse-Za caribou were generally healthy relative to neighboring subpopulations and repeat capture for penning did not appear to create accumulated health issues. Penned caribou had lower fecal cortisol levels and inflammation markers compared to free-ranging animals. This work provides a baseline assessment of southern mountain caribou health and provides guidance on maternal penning activities in support of caribou recovery.

Effects of Per- and Polyfluoroalkylated Substances on Female Reproduction.

Per- and poly-fluoroalkylated substances (PFAS) are a large group of chemicals that persist both in the environment and in the body. Legacy PFAS, e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid, are implicated as endocrine disruptors and reproductive and developmental toxicants in epidemiological and animal model studies. This review describes female reproductive outcomes of reported studies and includes where associative relationships between PFAS exposures and female reproductive outcomes have been observed as well as where those are absent. In animal models, studies in which PFAS are documented to cause toxicity and where effects are lacking are described. Discrepancies exist in both human and animal studies and are likely attributable to human geographical contamination, developmental status, duration of exposure, and PFAS chemical identity. Similarly, in animal investigations, the model used, exposure paradigm, and developmental status of the female are important and vary widely in documented studies. Taken together, support for PFAS as reproductive and developmental toxicants exists, although the disparity in study conditions and human exposures contribute to the variation in effects noted.

Can Probiotics Play a Major Role as an Adjunctive Therapy in Treatment of Bacterial Vaginosis?

Background: Bacterial Vaginosis is one of the most common causes of abnormal vaginal discharge in women of reproductive age, which can have a major impact on quality of life. Although the treatment course of oral metronidazole for 7 days results in curative rate of 70%–80% at four weeks of treatment, but is associated with high rates of recurrence occurred within twelve months, reaching up to 40%–50%. Methods: A Randomized Prospective Interventional Study was done on 1000 reproductive age group females (pregnant or non-pregnant) diagnosed with bacterial vaginosis from November 2020 to October 2022 at department of Obstetrics & Gynaecology, Kanpur. The study group were divided into two subgroups - Group 1 were given metronidazole 500 mg for 7 days and probiotics for 14 days and group 2 were given metronidazole 500 mg for 7 days and placebo for 14 days. The patients were followed after 3 months to know the recurrence. Results: Majority of patients belonged to rural background (63.1%) with lower socioeconomic (46.6%) and belong to age group 20-35 years. It was observed that there was significant change in Amsel’s criteria and Nugent’s scoring in Group 1 as compared to Group 2. The rate of recurrence at the end of the treatment for Amsel’s criteria in group 1 were 1.03 as compared to group 2 was 1.68 and for Nugent’s scoring, the rate of recurrence at the end of treatment in group 1 was 3.17 as compared to group 2 was 4.78. Conclusion: Probiotics can be considered as one the adjuvant therapy for treating bacterial vaginosis and re-establishing equilibrium in the vaginal microflora thus, preventing the recurrences.

Developmental exposure to environmentally relevant doses of phthalates alters the neural control of male and female reproduction in mice

The present study aims to analyze the effects of developmental exposure to phthalates at environmentally relevant doses on the neural control of male and female reproduction. For this purpose, C57Bl/6J mice were exposed to di-(2-ethylexyl) phthalate (DEHP) alone (5 or 50 μg/kg/d), or DEHP (5 μg/kg/d) in a phthalate mixture. Exposure through diet started 6 weeks before the first mating and lasted until weaning of litters from the second gestation (multiparous dams). Analyses of offspring born from multiparous dams exposed to DEHP alone or in a phthalate mixture showed that females experienced a delayed pubertal onset, and as adults they had prolonged estrous cyclicity and reduced Kiss1 expression in the preoptic area and mediobasal hypothalamus. Male littermates showed a reduced anogenital distance and delayed pubertal onset compared with controls. However, in adulthood the weight of androgen-sensitive organs and hypothalamic Kiss1 expression were unaffected, suggesting normal functioning of the male gonadotropic axis. Developmental exposure to DEHP alone or in a phthalate mixture reduced the ability of intact males and ovariectomized and hormonally primed females to attract a sexual partner and to express copulatory behaviors. In addition, females were unable to discriminate between male and female stimuli in the olfactory preference test. Social interaction was also impaired in females, while locomotor activity and anxiety-like behavior in both sexes were unaffected by the treatment. The sexual deficiencies were associated with reduced expression of the androgen receptor in the preoptic area and progesterone receptor in the mediobasal hypothalamus, the key regions involved in male and female sexual behavior, respectively. Thus, the neural structures controlling reproduction are vulnerable to developmental exposure to phthalates at environmentally relevant doses in male and female mice. Adult females had an impaired gonadotropic axis and showed more affected behaviors than adult males.

Bmal1 regulates female reproduction in mice via the hypothalamic-pituitary-ovarian axis.

The hypothalamic-pituitary-gonadal axis (HPG) is the key neuroendocrine axis involved in reproductive regulation. Brain and muscle ARNT-like protein 1 (Bmal1) participates in regulating the metabolism of various endocrine hormones. However, the regulation of Bmal1 on HPG and female fertility is unclear. This study aims to explore the regulation of female reproduction by Bmal1 via the HPG axis in mice. Bmal1-knockout (Ko) mice were generated using the CRISPR/Cas9 technology. The structure, function, and estrous cycle of ovarian in Bmal1 Ko female mice were measured. The key genes and proteins of the HPG axis involved in regulating female reproduction were examined through transcriptome analysis and then verified by RT-PCR, immunohistochemistry, and western blot. Furthermore, the fertility of female mice was detected after intervening prolactin (PRL) and progesterone (Pg) in Bmal1 ko mice. The number of offspring and ovarian weight were significantly lower in Bmal1-Ko mice than in wild-type (Wt) mice. In Bmal1-Ko mice, ovarian cells were arranged loosely and irregularly, and the total number of follicles was significantly reduced. No corpus luteum was found in the ovaries. Vaginal smears revealed that Bmal1-Ko mice had an irregular estrus cycle. In Bmal1-Ko mice, Star expression was decreased, PRL and luteinizing hormone (LH) levels were increased, and dopamine (DA) and Pg levels were decreased. Inhibition of PRL partially recovered the estrous cycle, corpus luteum formation, and Star expression in the ovaries. Pg supplementation promoted embryo implantation in Bmal1-Ko female mice. Bmal1 Ko increases serum PRL levels in female mice likely by reducing DA levels, thus affecting luteal formation, resulting in decreased Star expression and Pg production, hindering female reproduction. Inhibition of PRL or restoration of Pg can partially restore reproductive capacity in female Bmal1-Ko mice. Thus, Bmal1 may regulate female reproduction via the HPG axis in mice, suggesting that Bmal1 is a potential target to treat female infertility.

Hydrogen sulfide and its role in female reproduction.

Hydrogen sulfide (H2S) is a gaseous signaling molecule produced in the body by three enzymes: cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S is crucial in various physiological processes associated with female mammalian reproduction. These include estrus cycle, oocyte maturation, oocyte aging, ovulation, embryo transport and early embryo development, the development of the placenta and fetal membranes, pregnancy, and the initiation of labor. Despite the confirmed presence of H2S-producing enzymes in all female reproductive tissues, as described in this review, the exact mechanisms of H2S action in these tissues remain in most cases unclear. Therefore, this review aims to summarize the knowledge about the presence and effects of H2S in these tissues and outline possible signaling pathways that mediate these effects. Understanding these pathways may lead to the development of new therapeutic strategies in the field of women's health and perinatal medicine.

Toxic Effects of Methamphetamine on Reproductive Systems, Embryo Development, and Newborns: An Evidence-Based Review.

Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.

Melatonin improves mouse oocyte quality from 2-ethylhexyl diphenyl phosphate-induced toxicity by enhancing mitochondrial function

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

UCHL1 promotes the proliferation of porcine granulosa cells by stabilizing CCNB1

BackgroundThe proliferation of porcine ovarian granulosa cells (GCs) is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis. Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) regulates female reproduction, especially in ovarian development. However, the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear.ResultsUCHL1 overexpression promoted GC proliferation, and knockdown had the opposite effect. UCHL1 is directly bound to cyclin B1 (CCNB1), prolonging the half-life of CCNB1 and inhibiting its degradation, thereby promoting GC proliferation. What’s more, a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs.ConclusionsUCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1, and isovitexin enhanced the enzyme activity of UCHL1. These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.

High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices.

Excessive calorie intake poses a significant threat to female fertility, leading to hormonal imbalances and reproductive challenges. Overconsumption of unhealthy fats exacerbates ovarian dysfunction, with an overproduction of reactive oxygen species causing oxidative stress, impairing ovarian follicle development and leading to irregular ovulation and premature ovarian failure. Interest in biological matrices with high antioxidant properties to combat diet-related oxidative stress has grown, as they contain various bioactive factors crucial for neutralizing free radicals potentially preventing female reproductive health. This systematic review evaluates the female reproductive impact of biological matrices in mitigating oxidative damages induced by over calory habits and, in particular, high fat diets. A comparative approach among mammalian models was utilized to interpret literature available data. This approach specifically investigates the antioxidant mechanisms of biological matrices on early and late ovarian folliculogenesis, under physiological and hormone-induced female reproductive cycle. Adhering to the PRISMA 2020 guidelines, only English-language publications from peer-reviewed international indexes were considered. The analysis of 121 publications meeting the inclusion criteria facilitated the identification of crucial components of biological matrices. These components, including carbocyclic sugars, phytonutrients, organosulfur compounds, and vitamins, were evaluated for their impact on ovarian follicle resilience, oocyte quality, and reproductive lifespan. The detrimental effects of oxidative stress on female fertility, particularly exacerbated by high saturated fat diets, are well-documented. In vivo studies across mammalian preclinical models have underscored the potential of antioxidants derived from biological matrices to mitigate diet-induced conditions. These antioxidants enhance steroidogenesis and ovarian follicle development, thereby improving oocyte quality. Additionally, discussions within these publications emphasized the clinical significance of these biological matrices, translating research findings into practical applications for female health. Further research is essential to fully exploit the potential of these matrices in enhancing female reproduction and mitigating the effects of diets rich in fatty acids. This requires intensified in vitro studies and comprehensive collection of in vivo data before clinical trials. The promotion of ovarian resilience offers promising avenues for enhancing understanding and advancing female reproductive health world-wide.

Edukasi Literasi Kesehatan Reproduksi tentang Manajemen Preventif Leukorhea pada Santriwati

Teenager is an age group that is in a transitional period of human development. The transition period is the process of biological maturation into adults who can reproduce sexually and has the potential for all the consequences of sexual activity. Vaginal discharge is a problem that is often encountered after women experience puberty and may indicate a normal phenomenon, an infection, or other conditions. Healthy, clean-living behavior related to reproductive health in teenagers has a significant correlation with the level of knowledge and daily behavior of teenagers that affect leukorrhea. To increase the awareness of female students at the Modern Assalam Islamic Boarding School regarding clean and healthy living behavior in the field of healthy female reproduction system with support from health professionals and preventive education on leucorrhoea. This service activity was conducted with a total of 60 participants who were involved in filling out the pretest and post-test. The activity phase included initial studies through student-teacher discussions, preparation of learning materials and evaluation methods, and implementation of learning activities and evaluations. A total of 60 female students who took part in this reproductive health education activity got a preventive education knowledge, proved by comparing the pretest scores before the health education activity was carried out and the post-test after the educational activity. A significant increase was obtained with a rate of 93%. Activities related to leucorrhoea in female students show the effectiveness of significant improvement in the knowledge and enthusiasm of the participants.