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Pyriproxyfen (PPF) is an insecticide used in agriculture, which is approved for use in drinking water tanks for human consumption. However, some studies indicate that it may act as an endocrine disruptor and affect nontarget organisms. This study aimed to evaluate the effects of PPF on reproduction and general health status in female mice exposed from pre‐puberty to adulthood. In the first experiment, females were treated by gavage from postnatal day (PND) 23 to (PND) 75 and were distributed into three experimental groups: control (vehicle), PPF 0.1 mg/kg, and PPF 1 mg/kg. Female mice were assessed for the age of puberty onset, body mass, water and food consumption, and the estrous cycle. On PDN 75, a subgroup was euthanized, when vital and reproductive organs were collected and weighed. The thyroid, ovary, and uterus were evaluated for histomorphometry. The other subgroup was assessed in relation to reproductive performance and fetal parameters. In a second experiment, the uterotrophic assay was performed with juvenile females (PND 18) using doses of 0.01, 0.1, or 1 mg/kg of PPF. PPF treatment reduced thyroid mass and increased liver mass. Furthermore, there was an increase in ovarian interstitial tissue and, in the uterus, a decrease in the thickness of the endometrial stroma with reduced content of collagen fibers. There was also a reduction of 30% in pregnancy rate in the treated groups and an increase in the frequency of fetal death. This study suggests that, based on this experimental model, the insecticide may pose a reproductive risk for females chronically exposed to the substance from the pre‐pubertal period until adulthood. These results raise concerns about prolonged exposure of women to the same compound. [ABSTRACT FROM AUTHOR]

Abstract Background The relationship between A Body Shape Index (ABSI) and female infertility is not well understood. ABSI, a novel anthropometric measure, is gaining recognition for its ability to more accurately capture visceral fat characteristics than traditional metrics like BMI. This study aims to explore the association between ABSI and female infertility, considering its potential applications in medical screening and risk assessment. Methods This cross-sectional study analyzed data from the NHANES from 2013 to 2020. Female infertility was assessed through reproductive health questionnaires, and ABSI was calculated using waist circumference, BMI, and height. Weighted logistic regression models and trend tests were used to evaluate the association between ABSI and female infertility. Restricted cubic splines (RCS) were employed to explore potential nonlinear relationships. Subgroup analyses were conducted to examine the consistency of the association across various demographic and health-related factors. Sensitivity analyses were also performed, including the exclusion of participants with missing covariate data, the application of propensity score matching, and restricting the analysis to women aged 20–45 years. Results The study included 3,718 participants, 433 of whom were diagnosed with infertility. Higher ABSI was associated with an increased risk of female infertility (OR = 1.56, 95% CI: 1.21-2.00, P = 0.001), as demonstrated by weighted logistic regression and trend tests. Women in the highest ABSI quartile had a significantly higher prevalence of infertility compared to those in the lowest quartile (OR = 1.73, 95% CI: 1.27–2.37, P = 0.001). RCS curves indicated a linear positive relationship between ABSI and infertility risk, with a critical value at 0.079. Subgroup and sensitivity analyses confirmed the stability of these findings. Conclusion This study demonstrates a positive linear relationship between ABSI and the risk of female infertility. The use of a simple, non-invasive ABSI measurement could facilitate the early identification of high-risk individuals in large-scale screenings, potentially helping to prevent or reduce the incidence of infertility.

In addition to preventing precocious larval metamorphosis, juvenile hormone (JH), synthesized in corpora allata (CA), is known to stimulate female reproduction of insects. JH titer is extremely low or absent during metamorphosis, but thereafter rapidly increases in the previtellogenic stage and rises to a peak in the vitellogenic phase. However, the mechanisms underlying the biosynthesis of high levels of JH in adults remain unclear. We found in this study that 12 genes involved in JH synthesis pathway were highly expressed in the CA of adult locusts. By transcriptome analysis and quantitative real‐time – polymerase chain reaction validation, a total of 106 evolutionary conserved micro RNAs (miRNAs) and 163 species‐specific miRNAs were identified in locust CA. Dual‐luciferase assay revealed that 17 miRNAs bound to 10 JH synthesis genes (JHSGs) and downregulated their expression. These miRNAs were expressed in low levels during vitellogenic stage, which was oppositive from that of targeting JHSGs. Six miRNAs including miR‐971‐3p, miR‐31a, miR‐9‐5p, miR‐1‐3p, miR‐315, and miR‐282 were selected for function study. Co‐application of agomiRs resulted in significantly decreased levels of targeting JHSGs, accompanied by significantly reduced vitellogenin expression as well as arrested ovarian development. The data suggest that multiple miRNAs expressed synchronously at low levels in the vitellogenic phase, thereby ensuring the high levels of JHSG expression to facilitate JH biosynthesis required for JH‐dependent female reproduction. The findings provide important information for deciphering miRNA—messenger RNA modules for JH biosynthesis as well as JH regulation of insect metamorphosis and reproduction. [ABSTRACT FROM AUTHOR]

Ovarian cells, including oocytes, granulosa/cumulus cells, theca cells, and stromal cells, contain abundant mitochondria, which play indispensable roles in the processes of ovarian follicle development. Ovarian function is closely controlled by mitochondrial proteostasis and mitostasis. While mitochondrial proteostasis and mitostasis are disturbed by several factors, leading to dysfunction of ovarian function and initiating the mitochondrial unfolded protein response (UPRmt) and mitophagy to maintain or recover ovarian function and mitochondrial function, clear interactions between the 2 pathways in the ovary have not been fully elucidated. Here, we comprehensively summarize the molecular networks or regulatory mechanisms behind further mitochondrial research in the ovary. This review provides novel insights into the interactions between the UPRmt and mitophagy in ovarian functions. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects women of reproductive age. It is commonly linked to abnormal secretion of sex hormones, leading to disruptions in normal ovarian function. Vitamin E, a powerful lipid-soluble vitamin, has been extensively reported to have numerous positive health effects on the female reproductive system. Despite the existing studies, specific reports on the effects of vitamin E on hormonal regulations in PCOS are limited. Therefore, this paper aims to review the available reports on this topic, providing a reference for future studies on vitamin E and PCOS. [ABSTRACT FROM AUTHOR]

PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The endometrium plays a fundamental role in the reproductive system yet many etiologies of infertility-related endometrial diseases such as endometriosis, adenomyosis, Asherman’s syndrome or endometrial cancer remain unknown. There are currently no treatments that minimize the effects of this devastating disorder. Appropriate model systems that closely mimic the architecture and function of the endometrium in healthy and pathological states are needed to understand the underlying molecular pathways and develop novel or more effective treatments. This review summarizes the key milestones of in vitro culture models of the human endometrium throughout history, as well as the applications of advanced bioengineering techniques in the modelling of both healthy and pathological endometrium. Opportunities for future approaches are also discussed.

Religions are often acknowledged for their ability to provoke social, psychological, and physiological transformation, prompting recurrent studies in social and human sciences. Within this analytical domain, understanding ailments and methods of healing through various practices —rituals, cosmologies, and divinations— has been extensively explored. However, research on female reproductive ailments and corresponding intervention methods remains nascent in certain religious denominations, such as African-derived religions like the Regla de Ocha (Santería) in Cuba. The purpose of this article is to shed light on the healing of female reproductive ailments through the diloggún oracle utilized in the Regla de Ocha. Conducted between December 2022 and January 2023 in Santa Marta, Cárdenas, Cuba, our research adopts an ethnographic and narrative approach, placing reflexi-vity on our experiences at the forefront of our discussions. The research, from which our arguments derive, was conducted between December 2022 and January 2023 in Santa Marta, Cárdenas, Cuba. Methodologically, it adopts an ethnographic and narrative approach, placing reflexivity on our experiences at the forefront of our discussions. Consequently, it not only delineates the processes inherent in the practice of this oracle and its socio-spiritual impacts concerning potential realms of well-being but also advocates for conceptual and theoretical-methodological enhancements regarding healing. The article contributes to the evolving the incipient understanding of the connections between female fertility and healing within the Regla de Ocha and the intricate relationships among well-being, discomfort, and spirituality intrinsic to this religious system.

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. [ABSTRACT FROM AUTHOR]

The mouse estrous cycle is divided into four stages: proestrus (P), estrus (E), metestrus (M), and diestrus (D). The estrous cycle affects reproductive hormone levels in a wide variety of tissues. Therefore, to obtain reliable results from female mice, it is important to know the estrous cycle stage during sampling. The stage can be analyzed from a vaginal smear under a microscope. However, it is time-consuming, and the results vary between evaluators. Here, we present an accurate and reproducible method for staging the mouse estrous cycle in digital whole-slide images (WSIs) of vaginal smears. We developed a model using a deep convolutional neural network (CNN) in a cloud-based platform, Aiforia Create. The CNN was trained by supervised pixel-level multiclass semantic segmentation of image features from 171 hematoxylin-stained samples. The model was validated by comparing the results obtained by CNN with those of four independent researchers. The validation data included three separate studies comprising altogether 148 slides. The total agreement attested by the Fleiss kappa value between the validators and the CNN was excellent (0.75), and when D, E, and P were analyzed separately, the kappa values were 0.89, 0.79, and 0.74, respectively. The M stage is short and not well defined by the researchers. Thus, identification of the M stage by the CNN was challenging due to the lack of proper ground truth, and the kappa value was 0.26. We conclude that our model is reliable and effective for classifying the estrous cycle stages in female mice. [ABSTRACT FROM AUTHOR]

Important differences in health that are closely linked with social disadvantage exist within and between countries. According to the World Health Organization, life expectancy and good health continue to increase in many parts of the world, but fail to improve in other parts of the world, indicating that differences in life expectancy and health arise due to the circumstances in which people grow, live, work, and age, and the systems put in place to deal with illness. Marginalized communities experience higher rates of certain diseases and more deaths compared to the general population, indicating a profound disparity in health status. Although several factors place marginalized communities at high risk for poor health outcomes, one important factor is exposure to air pollutants. Marginalized communities and minorities are exposed to higher levels of air pollutants than the majority population. Interestingly, a link exists between air pollutant exposure and adverse reproductive outcomes, suggesting that marginalized communities may have increased reproductive disorders due to increased exposure to air pollutants compared to the general population. This review summarizes different studies showing that marginalized communities have higher exposure to air pollutants, the types of air pollutants present in our environment, and the associations between air pollution and adverse reproductive outcomes, focusing on marginalized communities. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib is a Janus kinase (JAK) 1 selective inhibitor approved for the treatment of atopic dermatitis. Female reproductive tissues were unaffected in general toxicity studies, but an initial female rat fertility study resulted in adverse effects at all doses evaluated. A second rat fertility study was conducted to evaluate lower doses and potential for recovery. Methods: This second study had 4 groups of 20 females each administered abrocitinib (0, 3, 10, or 70 mg/kg/day) 2 weeks prior to cohabitation through gestation day (GD) 7. In addition, 2 groups of 20 rats (0 or 70 mg/kg/day) were dosed for 3 weeks followed by a 4‐week recovery period before mating. All mated females were evaluated on GD 14. Results: No effects were observed at ≤10 mg/kg/day. At 70 mg/kg/day (29x human exposure), decreased pregnancy rate, implantation sites, and viable embryos were observed. All these effects reversed 4 weeks after the last dose. Conclusions: Based on these data and literature on the potential role of JAK signaling in implantation, we hypothesize that these effects may be related to JAK1 inhibition and, generally, that peri‐implantation effects such as these, in the absence of cycling or microscopic changes in nonpregnant female reproductive tissues, are anticipated to be reversible. [ABSTRACT FROM AUTHOR]

Simple Summary: We designed a common garden experiment to collect data on female reproductive traits from three populations of Takydromus sexlineatus, testing the hypothesis that geographically separated populations should share a species-specific pattern of seasonal shifts in reproductive allocation. Six traits differed among populations, with four of the six also differing among successive clutches. Females grew longer during the breeding season and produced more eggs in the first clutch than in the subsequent clutches; egg size was unchanged throughout the breeding season. After removing the influence of female size or postpartum mass we found that (1) postpartum body mass, clutch mass, and relative clutch mass were greater in the Wuzhishan population than in the Shaoguan and Zhaoqing populations; (2) egg size was greatest in the Wuzhishan population and smallest in the Zhaoqing population; and (3) clutch size was greatest in the Wuzhishan population and smallest in the Shaoguan population. Our data validate the hypothesis tested. We designed a common garden design to collect data on female reproductive traits from three populations of the southern grass lizard Takydromus sexlineatus, testing the hypothesis that a species-specific pattern of seasonal shifts in reproductive allocation should be shared by geographically separated populations. Of the seven examined traits, six differed among populations, with four of the six also differing among successive clutches. Females grew longer during the breeding season and produced more eggs in the first clutch than in the subsequent clutches; egg size was unchanged throughout the breeding season. After removing the influence of female size or postpartum body mass we found the following. First, postpartum body mass, clutch mass, and relative clutch mass were greater in the Wuzhishan population than in the Shaoguan and Zhaoqing populations. Second, egg size was greatest in the Wuzhishan population and smallest in the Zhaoqing population. Third, clutch size was greatest in the Wuzhishan population and smallest in the Shaoguan population. Females did not trade-off egg size against number within each population × clutch combination. Our study validates the hypothesis tested, supports the conventional view that reproductive output is highly linked to maternal body size in lizards, and follows the classic prediction that females with different amounts of resources to invest in reproduction should give priority to adjusting the total number rather than size of their offspring. [ABSTRACT FROM AUTHOR]

Obesity is becoming more common all across the world, causing a variety of health problems, including reproductive disruption. Although the novel, exercise-induced hormone irisin may affect the hypothalamus-pituitary-gonadal axis and reproductive function control, its impact on obesity-induced damage to the female reproductive system is not fully known. Hence, this study aimed to investigate the potential effects of irisin on reproductive hormones and reproductive organs in female rats with obesity induced by a high-fat diet. Forty female rats were divided into four groups: control, irisin, obese, and obese+irisin (n = 10 in each group). After simulating a high-fat diet-induced obesity model (via 60% kcal fat for 12 weeks) in the obese and obese+irisin groups, irisin (100 ng/kg/day via mini-osmotic pumps for about 28 days) was administered subcutaneously to the irisin and obese+irisin groups. Results showed that subcutaneous irisin perfusion increased serum luteinizing hormone (LH), the LH to follicle-stimulating hormone (FSH) ratio (LH/FSH), and progesterone levels while decreasing the histopathological damage in the ovaries of obese rats. On the other hand, endogenous irisin serum concentrations were similar in lean female rats and obese female rats with reproductive disorders. These results suggest that irisin may affect the reproductive axis in obese female rats. An increase in serum LH levels, which trigger ovarian steroidogenesis, and reducing histopathological changes in ovarian tissue could contribute to this effect. [ABSTRACT FROM AUTHOR]

Religions are often acknowledged for their ability to provoke social, psychological, and physiological transformation, prompting recurrent studies in social and human sciences. Within this analytical domain, understanding ailments and methods of healing through various practices --rituals, cosmologies, and divinations-- has been extensively explored. However, research on female reproductive ailments and corresponding intervention methods remains nascent in certain religious denominations, such as African-derived religions like the Regla de Ocha (Santería) in Cuba. The purpose of this article is to shed light on the healing of female reproductive ailments through the diloggún oracle utilized in the Regla de Ocha. Conducted between December 2022 and January 2023 in Santa Marta, Cárdenas, Cuba, our research adopts an ethnographic and narrative approach, placing reflexivity on our experiences at the forefront of our discussions. The research, from which our arguments derive, was conducted between December 2022 and January 2023 in Santa Marta, Cárdenas, Cuba. Methodologically, it adopts an ethnographic and narrative approach, placing reflexivity on our experiences at the forefront of our discussions. Consequently, it not only delineates the processes inherent in the practice of this oracle and its socio-spiritual impacts concerning potential realms of well-being but also advocates for conceptual and theoretical-methodological enhancements regarding healing. The article contributes to the evolving the incipient understanding of the connections between female fertility and healing within the Regla de Ocha and the intricate relationships among well-being, discomfort, and spirituality intrinsic to this religious system. [ABSTRACT FROM AUTHOR]

ABSTRACT: Embryonic mortality is a significant problem in the commercial duck industry worldwide. Therefore, identification of new biomarkers for duck embryo development is necessary. In the chicken (order Galliformes), we previously showed that chemerin is a hormone locally produced by the reproductive tract in hens, particularly in the magnum area, leading to its accumulation in the egg white and within the embryo annexes during embryonic development. We therefore hypothesized that the chemerin concentration in egg white could be a biomarker of egg performance and reproductive parameters in Pekin ducks (order Anseriformes). Thus, we collected eggs from Pekin ducks over a 5-d period at three stages of the laying period (before the laying peak, after the laying peak, and at the end of the laying period) to measure the chemerin concentrations in egg white by enzyme-linked immunosorbent assay. The chemerin concentration in egg white decreased during the laying period and was not associated with reproductive parameters. We found negative correlations between the chemerin level in egg white and the albumen weight. Reverse-transcriptase quantitative polymerase chain reaction showed that chemerin and its three receptors CMKLR1, GPR1, and CCRL2 were expressed in the reproductive tract and within allantoic and amniotic annexes during embryo development. Chemerin concentrations strongly increased in amniotic fluid on embryonic day 16 (ED16) when the egg white was transferred into the amniotic sac. Finally, chemerin inhibition in egg white by in ovo injections of anti-chemerin antibodies (0.01, 0.1, and 1 µg) increased the embryo mortality rate. These data demonstrate the important role of the chemerin system during egg formation and embryo development in Pekin ducks, suggesting their potential use as biomarkers for determining the quality of poultry eggs and embryo development.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme involved in many pathophysiological processes. Supplementation with NAD+ and its precursors has been demonstrated as an emerging therapeutic strategy for the diseases. NAD+ also plays an important role in the reproductive system. Here, we summarize the function of NAD+ in various reproductive diseases and review the application of NAD+ and its precursors in the preservation of reproductive capacity and the prevention of embryonic malformations. It is shown that NAD+ shows good promise as a therapeutic approach for saving reproductive capacity.

Abstract Background Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. Results We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. Conclusion Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.

Abstract Background Excessive energy intake in modern society has led to an epidemic surge in metabolic diseases, such as obesity and type 2 diabetes, posing profound threats to women’s reproductive health. However, the precise impact and underlying pathogenesis of energy excess on female reproduction remain unclear. Methods We established an obese and hyperglycemic female mouse model induced by a high-fat and high-sucrose (HFHS) diet, then reproductive phenotypes of these mice were evaluated by examing sexual hormones, estrous cycles, and ovarian morphologies. Transcriptomic and precise metabolomic analyses of the ovaries were performed to compare the molecular and metabolic changes in HFHS mice. Finally, orthogonal partial least squares discriminant analysis was performed to compare the similarities of traits between HFHS mice and women with polycystic ovary syndrome (PCOS). Results The HFHS mice displayed marked reproductive dysfunctions, including elevated serum testosterone and luteinizing hormone levels, irregular estrous cycles, and impaired folliculogenesis, mimicking the clinical manifestations of women with PCOS. Precise metabolomic overview suggested that HFHS diet disrupted amino acid metabolism in the ovaries of female mice. Additionally, transcriptional profiling revealed pronounced disturbances in ovarian steroid hormone biosynthesis and glucolipid metabolism in HFHS mice. Further multi-omics analyses unveiled prominent aberration in ovarian arginine biosynthesis pathway. Notably, comparisons between HFHS mice and a cohort of PCOS patients identified analogous reproductive and metabolic signatures. Conclusions Our results provide direct in vivo evidence for the detrimental effects of overnutrition on female reproduction and offer insights into the metabolic underpinnings of PCOS.

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a). [ABSTRACT FROM AUTHOR]

The exact neural construct underlying the dynamic secretion of gonadotrophin-releasing hormone (GnRH) has only recently been identified despite the detection of multiunit electrical activity volleys associated with pulsatile luteinising hormone (LH) secretion four decades ago. Since the discovery of kisspeptin/neurokinin B/dynorphin neurons in the mammalian hypothalamus, there has been much research into the role of this neuronal network in controlling the oscillatory secretion of gonadotrophin hormones. In this review, we provide an update of the progressive application of cutting-edge techniques combined with mathematical modelling by the neuroendocrine community, which are transforming the functional investigation of the GnRH pulse generator. Understanding the nature and function of the GnRH pulse generator can greatly inform a wide range of clinical studies investigating infertility treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Transmembrane emp24 domain (TMED) proteins serve as cellular "delivery workers", facilitating the transport and folding of specific proteins. TMED6, a member of the TMED protein γ subfamily, is highly expressed in various tissues in silkworms. In our study, we investigated expression in male and female tissues, as well as in pupal ovaries at different developmental stages. We observe that decreased TMED6 expression significantly reduces the number of eggs laid by female moths, leading to the accumulation of unlaid eggs in the abdomen. Furthermore, through in vivo and in vitro experiments in silkworms, we have discovered a close relationship between TMED6 and dopamine D2-like receptors (Dop2R). Dop2R plays a crucial role in neural signal transmission and can influence reproductive behavior in insects. BmTMED6 is closely associated with the dopamine receptor, suggesting its potential involvement in regulating the oviposition behavior of the moth through dopamine-related pathways. Our findings will have important implications for sericulture production in the future. Transmembrane emp24 domain (TMED) proteins have been extensively studied in mammalian embryonic development, immune regulation, and signal transduction. However, their role in insects, apart from Drosophila melanogaster, remains largely unexplored. Our previous study demonstrated the abundant expression of BmTMED6 across all stages and tissues of the silkworm. In this study, we investigate the function of BmTMED6 in reproduction. We observe significant differences in the expression of BmTMED6 between male and female silkworms, particularly in the head and fatboby, during the larval stage. Furthermore, qRT-PCR and WB analysis reveal substantial variation in BmTMED6 levels in the ovaries during pupal development, suggesting a potential association with silkworm female reproduction. We find that reducing TMED6 expression significantly decreases the number of eggs laid by female moths, leading to an accumulation of unlaid eggs in the abdomen. Moreover, downregulation of BmTMED6 leads to a decrease in the expression of BmDop2R1 and BmDop2R2, while overexpression of BmTMED6 in vitro has the opposite effect. These indicate that BmTMED6 plays a role in oviposition in female moths, potentially through the dopamine signaling pathway. This study provides a new regulatory mechanism for female reproduction in insects. [ABSTRACT FROM AUTHOR]

Hibernating mammals have annual cycles with strict timing of all processes including reproduction, yet female reproductive physiology is only poorly studied in such species. We investigated the estrous cycle in yellow ground squirrels (Spermophilus fulvus), which hibernate up to 9 months. Using vaginal cytology and serum progesterone and estradiol profiles, we identified proestrus, estrus, metestrus, and anestrus in the cycle. As in other rodents, predominance of cornified cells marked estrus, and an increase in the leukocyte number reflected metestrus. The only estrus in a year started, and then, pregnancy occurred mostly within 3 days after spring emergence. In one female, we noticed a copulatory plug for the first time for this species. The progesterone level increased from proestrus/estrus to pregnancy and decreased in the postlactation period. Estradiol concentration did not change significantly throughout the estrous cycle but varied among females and was consistently high in some of them. The hormone levels did not vary with female age despite smaller body size in yearling females than in older ones. During postlactation, progesterone concentration diminished toward hibernation, and we could not detect signs of prehibernation activation of the female reproductive system. Probably, gonadal preparation in S. fulvus females proceeds at periodic arousals during hibernation. Our data showed fast transitions between phases of the female estrous cycle and early maturation of juvenile females, consistently with the hypothesis of the fast life-history strategy of S. fulvus. [ABSTRACT FROM AUTHOR]

Grapes are an economically important fruit crop, and their polyphenols (mainly phenolic acids, flavanols, flavonols, anthocyanins, proanthocyanidins, and stilbenes) can exert a wide range of health benefits as an interesting and valuable dietary supplement for natural complementary therapy. However, their potential physiological and therapeutic actions on reproductive processes have not been sufficiently elucidated. This evidence-based study presents current knowledge of grape extracts and polyphenols, as well as their properties and therapeutical actions in relation to female reproduction in a nutshell. Grape extract, and its polyphenols such as resveratrol, proanthocyanidin B2 or delphinidin may influence female reproductive physiology and pathology, as well as regulate multiple signaling pathways related to reproductive hormones, steroid hormones receptors, intracellular regulators of oxidative stress and subsequent inflammation, apoptosis, and proliferation. Their role in the management of ovarian cancer, age-related reproductive insufficiency, ovarian ischemia, PCOS, or menopausal syndrome has been indicated. In particular, the potential involvement of grapeseed extracts and/or proanthocyanidin B2 and delphinidin on ovarian steroidogenesis, oocyte maturation, and developmental capacity has been implicated, albeit at different regulatory levels. Grape polyphenols exert awide range of health benefits posing grape extract as an interesting and valuable dietary supplement for natural complementary therapy. This evidence-based study focuses on the actions of grapeseed extract and grape polyphenols on female reproductive processes at various regulatory levels and multiple signalling pathways by regulating reproductive hormones (GnRH, gonadotropins, prolactin, steroid hormones, IGFBP), steroid receptors, markers of proliferation and apoptosis. However, lack of knowledge of standardized dosages so far limits their clinical application despite the wide range of their biological and therapeutic potentials. [ABSTRACT FROM AUTHOR]

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.

PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms.

Obesity is becoming more common all across the world, causing a variety of health problems, including reproductive disruption. Although the novel, exercise-induced hormone irisin may affect the hypothalamus-pituitary-gonadal axis and reproductive function control, its impact on obesity-induced damage to the female reproductive system is not fully known. Hence, this study aimed to investigate the potential effects of irisin on reproductive hormones and reproductive organs in female rats with obesity induced by a high-fat diet. Forty female rats were divided into four groups: control, irisin, obese, and obese+irisin (n = 10 in each group). After simulating a high-fat diet-induced obesity model (via 60% kcal fat for 12 weeks) in the obese and obese+irisin groups, irisin (100 ng/kg/day via mini-osmotic pumps for about 28 days) was administered subcutaneously to the irisin and obese+irisin groups. Results showed that subcutaneous irisin perfusion increased serum luteinizing hormone (LH), the LH to follicle-stimulating hormone (FSH) ratio (LH/FSH), and progesterone levels while decreasing the histopathological damage in the ovaries of obese rats. On the other hand, endogenous irisin serum concentrations were similar in lean female rats and obese female rats with reproductive disorders. These results suggest that irisin may affect the reproductive axis in obese female rats. An increase in serum LH levels, which trigger ovarian steroidogenesis, and reducing histopathological changes in ovarian tissue could contribute to this effect. Učinki irisina na reproduktivni sistem debelih samic podgan, povzročeni s prehrano z visoko vsebnostjo maščob Izvleček: Debelost je vse pogostejša po vsem svetu in povzroča različne zdravstvene težave, vključno z motnjami reprodukcije. Čeprav hormon irisin, ki se izloča med vadbo, lahko vpliva na hipotalamično-hipofizno-gonadno os in reproduktivno funkcijo, njegov vpliv na z debelostjo povezane poškodbe ženskega reproduktivnega sistema ni povsem znan. Zato je bil namen te študije raziskati morebitne učinke irisina na reproduktivne hormone in reproduktivne organe pri samicah podgan z debelostjo, povzročeno s prehrano z visoko vsebnostjo maščob. Štirideset samic podgan smo razdelili v štiri skupine: kontrola, irisin, debelost, debelost+irisin (n=10 v vsaki skupini). Po 12 tednih simulacije modela debelosti, povzročene s prehrano z visoko vsebnostjo maščob (60 % kcal maščobe), smo v skupinah debelost in debelostjo+irisin podganam podkožno dajali irisin (100 ng/kg/dan prek mini-osmotskih črpalk približno 28 dni). Podkožna aplikacija irisina je povečala serumski luteinizirajoči hormon (LH), razmerje med LH in folikle stimulirajočim hormonom (FSH) (LH/FSH) in raven progesterona, hkrati pa zmanjšala histopatološke poškodbe v jajčnikih debelih podgan. Vendar pa so bile koncentracije endogenega irisina v serumu vitkih in debelih podgan z reproduktivnimi motnjami podobne. Rezultati kažejo, da bi irisin lahko vplival na reproduktivno os debelih podgan. K temu učinku bi lahko prispevala povečanje serumske koncentracije LH, kar sproža steroidogenezo jajčnikov, ter zmanjšanje histopatoloških sprememb tkiva jajčnikov. Ključne besede: irisin; debelost; hormoni; jajčnik; apoptoza; reprodukcija pri samicah

Bisphenol A (BPA) is an endocrine disruptor of potential reproductive toxicities. Increasingly research elucidated that BPA exposure to the environment would change the epigenetic modifications of transcriptome, but the mechanism by which BPA affects m6A methylation in interfering with female reproductive health remains uncertain. Therefore, this study preliminarily proposed and tested the hypothesis that BPA exposure alters the m6A modification level in transcripts in female ovarian granulosa cells. After BPA was exposed to granulosa cells for 24 h, RNA methylation related regulatory genes (such as METTL3, METTL14, ALKBH5, FTO) and the global m6A levels showed significant differences. Next, we applied MERIP-seq analysis to obtain information on the genome-wide m6A modification changes and identified 1595 differentially methylated mRNA transcripts, and 50 differentially methylated lncRNA transcripts. Further joint analysis of gene common expression showed that 33 genes were hypermethylated and up-regulated, 71 were hypermethylated and down-regulated, 49 were hypomethylated and up-regulated, and 20 were hypomethylated and down-regulated. Enriched Gene Ontology (GO) and biological pathway analysis revealed that these unique genes were mainly enriched in lipid metabolism, cell proliferation, and apoptosis related pathways. Six of these genes (mRNAs IMPA1, MCOLN1, DCTN3, BRCA2, and lncRNAs MALAT1, XIST) were validated using RT-qPCR and IGV software. Through comprehensive analysis of epitranscriptome and protein-protein interaction (PPI) data, lncRNAs MALAT1 and XIST are expected to serve as new markers for BPA interfering with the female reproductive system. In brief, these data show a novel and necessary connection between the damage of BPA exposure on female ovarian granulosa cells and RNA methylation modification.

Grapes are an economically important fruit crop, and their polyphenols (mainly phenolic acids, flavanols, flavonols, anthocyanins, proanthocyanidins, and stilbenes) can exert a wide range of health benefits as an interesting and valuable dietary supplement for natural complementary therapy. However, their potential physiological and therapeutic actions on reproductive processes have not been sufficiently elucidated. This evidence-based study presents current knowledge of grape extracts and polyphenols, as well as their properties and therapeutical actions in relation to female reproduction in a nutshell. Grape extract, and its polyphenols such as resveratrol, proanthocyanidin B2 or delphinidin may influence female reproductive physiology and pathology, as well as regulate multiple signaling pathways related to reproductive hormones, steroid hormones receptors, intracellular regulators of oxidative stress and subsequent inflammation, apoptosis, and proliferation. Their role in the management of ovarian cancer, age-related reproductive insufficiency, ovarian ischemia, PCOS, or menopausal syndrome has been indicated. In particular, the potential involvement of grapeseed extracts and/or proanthocyanidin B2 and delphinidin on ovarian steroidogenesis, oocyte maturation, and developmental capacity has been implicated, albeit at different regulatory levels. Grape polyphenols exert a wide range of health benefits posing grape extract as an interesting and valuable dietary supplement for natural complementary therapy. This evidence-based study focuses on the actions of grapeseed extract and grape polyphenols on female reproductive processes at various regulatory levels and multiple signalling pathways by regulating reproductive hormones (GnRH, gonadotropins, prolactin, steroid hormones, IGFBP), steroid receptors, markers of proliferation and apoptosis. However, lack of knowledge of standardized dosages so far limits their clinical application despite the wide range of their biological and therapeutic potentials.

Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs. MED12 mutation-positive UFs (MED12-UFs) often develop multiple rather than solitary and have distinct gene expression profiles, DNA methylomes, transcriptomes, and proteomes. Gene expressions related to ECM organization and collagen-rich ECM components are upregulated, and impaired Mediator kinase activity and dysregulation of Wnt/ß-catenin signaling are identified in MED12-UFs. Clinically, the UF shrinking effect of gonadotropinreleasing hormone agonists and ulipristal acetate is dependent on the MED12 mutation status. Understanding of characteristics of MED12-UFs and functions of MED12 mutations for UF tumorigenesis may elucidate the pathophysiology of UFs, leading to the development of new therapeutic options in women with symptomatic UFs. [ABSTRACT FROM AUTHOR]

Organoids are three-dimensional cellular structures designed to recreate the biological characteristics of the body's native tissues and organs in vitro. There has been a recent surge in studies utilizing organoids due to their distinct advantages over traditional two-dimensional in vitro approaches. However, there is no consensus on how to define organoids. This literature review aims to clarify the concept of organoids and address the four fundamental questions pertaining to organoid models: (i) What constitutes organoids?—The cellular material. (ii) Where do organoids grow?—The extracellular scaffold. (iii) How are organoids maintained in vitro?—Via the culture media. (iv) Why are organoids suitable in vitro models?—They represent reproducible, stable, and scalable models for biological applications. Finally, this review provides an update on the organoid models employed within the female reproductive tract, underscoring their relevance in both basic biology and clinical applications. [ABSTRACT FROM AUTHOR]

A prevailing challenge when testing chemicals for their potential to cause female reproductive toxicity is the lack of appropriate toxicological test methods. We hypothesized that starting a 28-day in vivo toxicity study already at weaning, instead of in adulthood, would increase the sensitivity to detect endocrine disruptors due to the possibility of including assessment of pubertal onset. We compared the sensitivity of two rat studies using pubertal or adult exposure. We exposed the rats to two well-known human endocrine disruptors, the estrogen diethylstilbestrol (DES; 0.003, 0.012, 0.048 mg/kg bw/day) and the steroid synthesis inhibitor ketoconazole (KTZ; 3, 12, 48 mg/kg bw/day). Specifically, we addressed the impact on established endocrine-sensitive endpoints including day of vaginal opening (VO), estrous cyclicity, weights of reproductive organs and ovarian histology. After 28 days of exposure, starting either at weaning or at 9 weeks of age, DES exposure altered estrous cyclicity, reduced ovary weight as well as number of antral follicles and corpora lutea. By starting exposure at weaning, we could detect advanced day of VO in DES-exposed animals despite a lower body weight. Some endpoints were affected mainly with adult exposure, as DES increased liver weights in adulthood only. For KTZ, no effects were seen on time of VO, but adrenal and liver weights were increased in both exposure scenarios, and adult KTZ exposure also stimulated ovarian follicle growth. At first glance, this would indicate that a pubertal exposure scenario would be preferrable as timing of VO may serve as sensitive indicator of endocrine disruption by estrogenic mode of action. However, a higher sensitivity for other endocrine targets may be seen starting exposure in adulthood. Overall, starting a 28-day study at weaning with inclusion of VO assessment would mainly be recommended for substances showing estrogenic potential e.g., in vitro, whereas for other substances an adult exposure scenario may be recommended. [ABSTRACT FROM AUTHOR]

We designed a common garden design to collect data on female reproductive traits from three populations of the southern grass lizard Takydromus sexlineatus, testing the hypothesis that a species-specific pattern of seasonal shifts in reproductive allocation should be shared by geographically separated populations. Of the seven examined traits, six differed among populations, with four of the six also differing among successive clutches. Females grew longer during the breeding season and produced more eggs in the first clutch than in the subsequent clutches; egg size was unchanged throughout the breeding season. After removing the influence of female size or postpartum body mass we found the following. First, postpartum body mass, clutch mass, and relative clutch mass were greater in the Wuzhishan population than in the Shaoguan and Zhaoqing populations. Second, egg size was greatest in the Wuzhishan population and smallest in the Zhaoqing population. Third, clutch size was greatest in the Wuzhishan population and smallest in the Shaoguan population. Females did not trade-off egg size against number within each population × clutch combination. Our study validates the hypothesis tested, supports the conventional view that reproductive output is highly linked to maternal body size in lizards, and follows the classic prediction that females with different amounts of resources to invest in reproduction should give priority to adjusting the total number rather than size of their offspring.

A prevailing challenge when testing chemicals for their potential to cause female reproductive toxicity is the lack of appropriate toxicological test methods. We hypothesized that starting a 28-day in vivo toxicity study already at weaning, instead of in adulthood, would increase the sensitivity to detect endocrine disruptors due to the possibility of including assessment of pubertal onset. We compared the sensitivity of two rat studies using pubertal or adult exposure. We exposed the rats to two well-known human endocrine disruptors, the estrogen diethylstilbestrol (DES; 0.003, 0.012, 0.048 mg/kg bw/day) and the steroid synthesis inhibitor ketoconazole (KTZ; 3, 12, 48 mg/kg bw/day). Specifically, we addressed the impact on established endocrine-sensitive endpoints including day of vaginal opening (VO), estrous cyclicity, weights of reproductive organs and ovarian histology. After 28 days of exposure, starting either at weaning or at 9 weeks of age, DES exposure altered estrous cyclicity, reduced ovary weight as well as number of antral follicles and corpora lutea. By starting exposure at weaning, we could detect advanced day of VO in DES-exposed animals despite a lower body weight. Some endpoints were affected mainly with adult exposure, as DES increased liver weights in adulthood only. For KTZ, no effects were seen on time of VO, but adrenal and liver weights were increased in both exposure scenarios, and adult KTZ exposure also stimulated ovarian follicle growth. At first glance, this would indicate that a pubertal exposure scenario would be preferrable as timing of VO may serve as sensitive indicator of endocrine disruption by estrogenic mode of action. However, a higher sensitivity for other endocrine targets may be seen starting exposure in adulthood. Overall, starting a 28-day study at weaning with inclusion of VO assessment would mainly be recommended for substances showing estrogenic potential e.g., in vitro, whereas for other substances an adult exposure scenario may be recommended.

Environmental temperature rises are powerful stimuli that can alter both the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis (HPA). Heat stress has been shown to harm pregnancy outcomes such as causing spontaneous abortion, low birth weight, growth retardation and stillbirth. Supplementation of bee bread in pregnant rats under heat stress exposure has been shown to improve the pregnancy outcomes. However, whether supplementation of bee bread during heat stress exposure may also reduce the level of the stress hormone, corticosterone has yet been reported. Therefore, this study aims to determine the effect of bee bread on corticosterone level, progesterone level, oestradiol level and zonation of the adrenal cortex of pregnant rats under heat stress exposure. Pregnant rats were randomly categorised into four groups (n = 6): Control (C: standard feeding), Treatment 1 (T1: 0.5 g bee bread/kg body weight/day), Treatment 2 (T2: standard feeding with heat exposure), and Treatment 3 (T3: 0.5 g bee bread/kg body weight/day with heat exposure). Bee bread (0.5 g/kg body weight/day) was force-fed to pregnant rats through oral gavage beginning on day 0 of pregnancy and continuing until delivery. Heat stress was generated experimentally by putting both T2 and T3 rats in an egg incubator for 45 min daily at a temperature of 43°C till delivery. On a postnatal Day 21, dams were euthanised to assess serum corticosterone, progesterone, oestradiol levels and adrenal gland histology. Rats in the T2 group had a significantly (P < 0.05) increase in the zona fasciculata thickness (94.95 ± 1.55 µm) and higher corticosterone levels (49.57 ± 1.57 ng/mL) compared with control. However, supplementation of bee bread during heat stress was able to show an improvement in adrenal zona fasciculata thickness by decreasing to 79.89 ± 3.08 µm and corticosterone level reduced to 35.31 ± 1.73 ng/mL significantly (P < 0.05). Therefore, these findings may imply that bee bread is effective as a neutralizer in lowering the production of stress hormone. [ABSTRACT FROM AUTHOR]

Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women. [ABSTRACT FROM AUTHOR]

We analyzed the effects of pyriproxyfen (PPF) on oxidative stress and ovarian morphology in zebrafish. PPF (10−9 M) exposure increased reactive oxygen species generation in ovaries, in association with a decrease in glutathione content. The activities of glutathione S‐transferase, superoxide dismutase, and catalase were increased, while γ‐glutamyltransferase activity was not altered by pesticide treatment. The histology of ovarian tissue showed an increase in the number of previtellogenic oocytes I, and a decrease in the rate of vitellogenic oocyte (VIT) count, suggesting inhibition of follicular maturation. An increase in the thickness of the vitelline envelope was observed in VIT, as was a tendency toward an increase in atresia in the ovary of the PPF‐treated group. These findings indicate that the deleterious effect of PPF on ovarian maturation is mediated by a redox imbalance and oxidative damage. So, PPF acts as an endocrine disruptor chemical and may compromise fish reproduction by reducing female fertility. Pyriproxyfen (PPF), an endocrine disruptor chemical, exhibits a xenoestrogen‐like effect and compromise fish reproduction by reducing female fertility. The tissue damage induced by PPF during ovarian maturation is mediated by ROS formation, GSH depletion, and activated antioxidant enzymatic systems, probably in response to the oxidative insult. The pesticide‐induced oxidative stress might affect ovarian maturation, compromising fish reproduction and fertility. [ABSTRACT FROM AUTHOR]

Animal toxicological studies often fail to mimic the complexity of the human exposome, associating low doses, combined molecules and long-term exposure. Since the reproductive potential of a woman begins in the fetal ovary, the literature regarding the disruption of its reproductive health by environmental toxicants remains limited. Studies draw attention to follicle development, a major determinant for the quality of the oocyte, and the preimplantation embryo, as both of them are targets for epigenetic reprogramming. The "Folliculogenesis and Embryo Development EXPOsure to a mixture of toxicants: evaluation in the rabbit model" (FEDEXPO) project emerged from consideration of these limitations and aims to evaluate in the rabbit model the impacts of an exposure to a mixture of known and suspected endocrine disrupting chemicals (EDCs) during two specific windows, including folliculogenesis and preimplantation embryo development. The mixture combines eight environmental toxicants, namely perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), 2,2′4,4′-tetrabromodiphenyl ether (BDE-47), di(2-ethylhexyl) phthalate (DEHP) and bisphenol S (BPS), at relevant exposure levels for reproductive-aged women based on biomonitoring data. The project will be organized in order to assess the consequences of this exposure on the ovarian function of the directly exposed F0 females and monitor the development and health of the F1 offspring from the preimplantation stage. Emphasis will be made on the reproductive health of the offspring. Lastly, this multigenerational study will also tackle potential mechanisms for the inheritance of health disruption via the oocyte or the preimplantation embryo. [ABSTRACT FROM AUTHOR]

In bacteria, polymers of inorganic phosphates, particularly linear polyphosphate, are used as alternative phosphate donors for adenosine triphosphate production. A six-chain form of sodium metaphosphate, sodium hexametaphosphate (SHMP), is believed to have no physiological functions in mammalian cells. In this study, we explored the possible effects of SHMP on mammalian cells, using mouse oocytes, which are useful for observing various spatiotemporal intracellular changes. Fertilization-competent oocytes were isolated from the oviducts of superovulated mice and cultured in an SHMP-containing medium. In the absence of co-incubation with sperm, SHMP-treated oocytes frequently formed pronuclei and developed into two-cell embryos owing to the increase in calcium concentration in the cytoplasm. We discovered an intriguing role for SHMP as an initiator of calcium rise in mouse oocytes, presumably in a wide variety of mammalian cells. [ABSTRACT FROM AUTHOR]

Endocrine disruptors (EDs) are considered to have an impact on the function of reproductive axis at different levels as well on reproductive organs in both sexes. Complexity of female reproductive system influenced with various stressors including EDs lead to morphological and functional alterations. This is resulting in modulation of neuroendocrine regulation with consequent developmental irregularities and derangements, causative infertility, endometriosis as well as premature ovarian insufficiency or polycystic ovary syndrome. A number of experimental clues was obtained on female animal models using various EDs such as synthetic estrogens and phytoestrogens, neurotransmitters, pesticides or various chemicals. These substances lead towards consequent derangement of the neuroendocrine control of reproduction from early phases of reproductive development towards different phases of adult reproductive period. This text will address some novel insights into the effects of EDs on neuroendocrine regulation of gonadal axis, effects on ovaries as well on endometrium during implantation period. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority. Methods: Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian–Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results: We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32–1.52) for anxiety, 1.65 (95% CI: 1.44–1.89) for depression, 1.48 (95% CI: PR: 1.06–2.05) for eating disorders, and 1.20 (95% CI: 0.96–1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD. Conclusions: Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. Funding: The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence