Female Reproductive Outcomes Research Articles

Short-term polystyrene nanoplastic exposure alters zebrafish male and female germline and reproductive outcomes, unveiling pollutant-impacted molecular pathways

Nanoplastics pollution is a rising environmental concern whose impacts on biodiversity and human health are far from being understood. This is particularly salient in aquatic ecosystems, where the majority of species depend on external fertilization for reproduction. Here we evaluated the effects of a short-term exposure to engineered polystyrene nanoplastics (NPs) in the zebrafish germline to further explore their impact on reproduction. To this end, zebrafish (Danio rerio) were exposed to 5 mg/L of 45 nm polystyrene (PS)-NPs via water for 96 h. We show that, in males, nanoplastics induced testicular histological alterations with abnormal sperm clustering and chromatin compaction, resulting in viable spermatozoa but with reduced motility. Moreover, in females we observed an alteration in oocyte stages frequencies during oogenesis, possibly reflecting alterations in oocyte growth. RNA-sequencing analysis in male testis links nanoplastic induced alterations in the expression of genes involved in chromatin structure, meiosis and DNA double-strand break formation and repair progression, and gametes recognition. Flow cytometry analysis revealed that the observed effects in males were directly due to nanoplastics penetrating the testicular barrier and being internalized within germline cells. Overall, our results demonstrate that acute exposure to NPs can compromise reproductive fitness, underscoring the environmental and health impacts of NPs pollution.

Autophagy and Female Fertility: Mechanisms, Clinical Implications, and Emerging Therapies.

Autophagy, an evolutionarily conserved cellular mechanism essential for maintaining internal stability, plays a crucial function in female reproductive ability. In this review, we discuss the complex interplay between autophagy and several facets of female reproductive health, encompassing pregnancy, ovarian functions, gynecologic malignancies, endometriosis, and infertility. Existing research emphasizes the crucial significance of autophagy in embryo implantation, specifically in the endometrium, highlighting its necessity in ensuring proper fetal development. Although some knowledge has been gained, there is still a lack of research on the specific molecular impacts of autophagy on the quality of oocytes, the growth of follicles, and general reproductive health. Autophagy plays a role in the maturation, quality, and development of oocytes. It is also involved in reproductive aging, contributing to reductions in reproductive function that occur with age. This review explores the physiological functions of autophagy in the female reproductive system, its participation in reproductive toxicity, and its important connections with the endometrium and embryo. In addition, this study investigates the possibility of emerging treatment approaches that aim to modify autophagy, using both natural substances and synthetic molecules, to improve female fertility and reproductive outcomes. Additionally, this review intends to inspire future exploration into the intricate role of autophagy in female reproductive health by reviewing recent studies and pinpointing areas where current knowledge is lacking. Subsequent investigations should prioritize the conversion of these discoveries into practical uses in the medical field, which could potentially result in groundbreaking therapies for infertility and other difficulties related to reproduction. Therefore, gaining a comprehensive understanding of the many effects of autophagy on female fertility would not only further the field of reproductive biology but also open new possibilities for diagnostic and treatment methods.

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.

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose–response meta-analysis

BackgroundTo inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. MethodsWe conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults’ preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers’ data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose–response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. ResultsWe identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces).General public studies.From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97–1.34, 95% prediction interval (PI): 0.83–1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96–1.36, 95% PI: 0.84–1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02–1.24, 95% PI: 0.99–1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth.Occupational studies.In occupational studies, based on dose–response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94–1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DiscussionMost of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes.Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis.

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

Abstract B100: Perfluoroalkyl substances (PFAS) induce platinum resistance in ovarian cancer through altering mitochondrial function

Abstract Platinum resistance is a major barrier to the effective treatment of advanced-stage ovarian cancer; however, factors leading to the development of resistance are not well understood. In fact, the role of environmental endocrine disrupting chemicals, such as perfluoroalkyl substances (PFAS), have seldom been explored. This is important because select PFAS have been linked to adverse reproductive outcomes in females including endometriosis, oocyte apoptosis, infertility, and increased even ovarian cancer risk at very high exposure levels. The relationship between PFAS and adverse female reproductive outcomes, as well as reports of other endocrine disruptors leading to therapy resistance, led, in the current study, to the evaluation of the effect of PFAS exposure on response to carboplatin in ovarian cancer cells. We recently showed that select PFAS, at human-relevant concentrations, induced carboplatin resistance in OVCAR-3 and Caov-3 cells; however, the mechanism underlying the onset of resistance remains largely unknown. Since platinum-resistant ovarian cancer is characterized, in part, by increased mitochondrial networks and enhanced bioenergetic capacities, the central hypothesis of this study is that PFAS induce alterations to mitochondrial biology. Mitochondrial endpoints of interest included redox ratio and superoxide production. To measure redox ratio, nicotinamide dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which are inherently fluorescent, were measured using a fluorescence plate reader. Since NADH and FAD are metabolites produced via oxidative phosphorylation and glycolysis, evaluating redox ratio can provide an understanding of which pathway is preferred in the presence of environmental stimuli like PFAS. In OVCAR-3 and Caov-3 cells, baseline NADH:FAD ratios were 3.3 and 3.5, respectively. After 48 hours of PFAS exposure, NADH:FAD ratios of OVCAR-3 and Caov-3 cells ranged from 8-10 or 6-10, respectively. This increase after PFAS exposure could suggest enhanced energy production capabilities that warrant further investigation. As an additional measure, superoxide production was measured using flow cytometry. OVCAR-3 and Caov-3 cells were exposed to PFAS for 6 days prior to isolating cell pellets and incubating them with MitoSOX (mitochondrial) and SYTOX Blue (nuclear) dyes. After 15–30-minute incubations, samples were run on the flow cytometer. Compared to controls, superoxide production in PFAS-exposed ovarian cancer cells increased by up to 200%. Often, cancer cells have elevated levels of reactive oxygen species due to enhanced energy production and signaling pathways, thus this finding further suggests that PFAS affect mitochondrial energy pathways. Altogether, these data show that PFAS exposure, which can induce carboplatin resistance in OVCAR-3 and Caov-3 cells, increases redox ratios and superoxide production in ovarian cancer cells. Therefore, targeting alterations in mitochondrial biology arising from PFAS exposure using precision medicine could be effective in overcoming platinum resistance in ovarian cancer. Citation Format: Brittany P. Rickard, Marta Overchuk, Vesna A. Chappell, Carl D. Bortner, Victoria L. Bae-Jump, Suzanne E. Fenton, Imran Rizvi. Perfluoroalkyl substances (PFAS) induce platinum resistance in ovarian cancer through altering mitochondrial function [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B100.

Recent progress in metabolomics for analyzing common infertility conditions that affect ovarian function.

Numerous efforts have been undertaken to identify biomarkers associated with embryo and oocyte quality to improve the success rate of invitro fertilization. Metabolomics has gained traction for its ability to detect dynamic biological changes in real time and provide comprehensive metabolite profiles. This review synthesizes the most recent findings on metabolomic analysis of follicular fluid (FF) in clinical conditions leading to infertility, with a focus on the dynamics of energy metabolism and oocyte quality, and discusses future research directions. A literature search was conducted without time constraints. The metabolites present in FF originate from five primary pathways: glycolysis, oxidative phosphorylation, lipid metabolism and β-oxidation, nucleic acid synthesis, and ketogenesis. Metabolomic profiling can broadly categorize infertile women into two groups: those with infertility due to aging and endometriosis, and those with infertility associated with polycystic ovarian syndrome and obesity. In the former group, glycolysis and lipid metabolism are upregulated to compensate for mitochondrial dysfunction, whereas the latter group exhibits the opposite trend. Assessing the levels of glucose, pyruvate, lactate, and plasmalogens in FF may be valuable for evaluating oocyte quality. Metabolomic analysis, particularly focusing on energy metabolism in FF, holds promise for predicting female reproductive outcomes.

Food, nutrition, and fertility: from soil to fork

Food and nutrition-related factors, including foods and nutrients consumed, dietary patterns, use of dietary supplements, adiposity, and exposure to food-related environmental contaminants, have the potential to impact semen quality and male and female fertility; obstetric, fetal, and birth outcomes; and the health of future generations, but gaps in evidence remain. On 9 November 2022, Tufts University’s Friedman School of Nutrition Science and Policy and the school's Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships between food, nutrition, and fertility. Topics addressed included male fertility, female fertility and gestation, and intergenerational effects. This meeting report summarizes the presentations and deliberations from the meeting.Regarding male fertility, a positive association exists with a healthy dietary pattern, with high-quality evidence for semen quality and lower quality evidence for clinical outcomes. Folic acid and zinc supplementation have been found to not impact male fertility. In females, body weight status and other nutrition-related factors are linked to nearly half of all ovulation disorders, a leading cause of female infertility. Females with obesity have worse fertility treatment, pregnancy-related, and birth outcomes. Environmental contaminants found in food, water, or its packaging, including lead, perfluorinated alkyl substances, phthalates, and phenols, adversely impact female reproductive outcomes. Epigenetic research has found that maternal and paternal dietary-related factors can impact outcomes for future generations.Priority evidence gaps identified by meeting participants relate to the effects of nutrition and dietary patterns on fertility, gaps in communication regarding fertility optimization through changes in nutritional and environmental exposures, and interventions impacting germ cell mechanisms through dietary effects. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and fertility.

Prevalence of obesity and its impact on female reproductive health outcomes in Al-Baha Region: A retrospective assessment

Prevalence of obesity and its impact on female reproductive health outcomes in Al-Baha Region: A retrospective assessment

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.

P-698 Genetics and reproductive health outcomes: An Asian perspective

Abstract Study question Does genetics play a role in the reproductive outcomes in women undergoing assisted reproductive technology (ART)? Summary answer We describe a trend towards poorer reproductive outcomes associated with Asian women and ART. Subsequently, we posit a potential biological mechanism. What is known already In the last four decades, advances in assisted reproductive technology (ART) have afforded the possibility of conceiving a child to individuals who encounter fertility complications. However, a closer examination of the clinical outcomes of ART shows a stark contrast in Asian women compared to Caucasians, with the majority of studies reporting lower reproductive success among Asian women. In this study, a systematic review was performed to elucidate the genes associated with ART clinical outcomes, with a focus on Asian ethnicities. Concomitantly, we highlight the need for personalized medicine to bridge the gaps in female reproductive health. Study design, size, duration We performed a Pubmed and Embase database search, from inception to December 2022, to identify all studies which investigated the differential reproductive outcomes in Asian women compared to their Caucasian counterparts, genetic mutations contributing to fertility in Asian women and personalized medicine. Following the PRISMA workflow, the preliminary search yielded a total of 2,145 papers to be reviewed. Participants/materials, setting, methods Following the inclusion/exclusion criteria screening, 128 studies were analyzed (ART outcomes in Asians, n=75; Genetics on women’s reproductive health, n=38; Personalized medicine in Asians, n=15). As each research paper identified one or more genes/SNPs involved in female fertility and reproductive health, we took a step further and performed a pathway analysis of gene-sets using STRING in Cytoscape v3.4.0. Network analysis and biological process associations were performed using GSEA and MSigDB. Significant gene-sets were annotated if FDR<0.05. Main results and the role of chance We observed that age at menarche(AAM) was found to be correlated with the timing of the first pregnancy, with Hawaiians having the lowest age(22.2yrs) and Japanese women having the highest age(25.0yrs). LIN28 mutations were highly associated with AAM and prevalent in both Chinese and American populations. FMR1 was most associated with ovarian reserve, with BMP15, ESR1, INHA, PRIM, TMEM150B to a lesser extent. Finally, FSHR polymorphisms were found to affect IVF outcomes most significantly. Network analysis highlighted a close association between 5 genes; FMR1, FSHR, ESR1, BMP15 and INHA, through biological functions of ovarian follicle development, menstrual cycle and hyperpituitarism. Network analysis revealed 4 major biological pathways (ovarian follicle development, oocyte maturation, ovulation, steroidogenesis), as well as key proteins which are involved in female fertility and reproductive health outcomes. PI3K/Akt are critical regulators of ovarian function through primordial follicle maturation and granulosa cell proliferation. MAPK signaling is involved with gonadotrophin-releasing hormone which controls FSH and LH secretion while Gq/11 signaling is activated through LH receptor. Therefore, PI3K/Akt, MAPK and Gq/11 protein signaling pathway appear to be key components to a broad range of reproductive outcomes and represent potential pathways to target in future studies investigating ovarian, follicular and steroidogenesis dysfunction. Limitations, reasons for caution A large majority of the papers reviewed relied on the self-reporting of ethnicities, which can vary considerably in accordance to how an individual defines his or her own ethnicity. Hence, we could not exclude the possibility of reporting bias in the studies. Wider implications of the findings Leveraging these findings,we propose the development of a biomarker panel which would enhance patient stratification,moving towards personalized medicine to address every woman’s unique reproductive potential.With several countries reporting low fertility rates due to shifts in socio-economic and life priorities, this has strong implications for those who wish to delay childbearing. Trial registration number Not applicable

Trauma and female reproductive health across the lifecourse: motivating a research agenda for the future of women's health.

The aetiology behind many female reproductive disorders is poorly studied and incompletely understood despite the prevalence of such conditions and substantial burden they impose on women's lives. In light of evidence demonstrating a higher incidence of trauma exposure in women with many such disorders, we present a set of interlinked working hypotheses proposing relationships between traumatic events and reproductive and mental health that can define a research agenda to better understand reproductive outcomes from a trauma-informed perspective across the lifecourse. Additionally, we note the potential for racism to act as a traumatic experience, highlight the importance of considering the interaction between mental and reproductive health concerns, and propose several neuroendocrinological mechanisms by which traumatic experiences might increase the risk of adverse health outcomes in these domains. Finally, we emphasize the need for future primary research investigating the proposed pathways between traumatic experiences and adverse female reproductive outcomes.

Advances in Research on the Relationship between Vaginal Microbiota and Adverse Pregnancy Outcomes and Gynecological Diseases.

The human microbiota inhabiting different parts of the body has been shown to have a significant impact on human health, with the gut microbiota being the most extensively studied in relation to disease. However, the vaginal microbiota is also an essential commensal microbiota in the female body that plays a crucial role in female health. Despite receiving less attention than gut microbiota, its importance in regulating reproductive immunity and its complex dynamic properties have been increasingly recognized in recent years. Advances in research on the relationship between vaginal microbiota and pregnancy outcomes & gynecological diseases in women have shed light on the importance of maintaining a healthy vaginal microbiota. In this review, we aim to compile recent developments in the study of the vaginal microbial ecosystem and its role in female health and reproductive outcomes. We provide a comprehensive account of the normal vaginal microbiota, the association between the vaginal microbiota and pregnancy outcomes, and the impact of the vaginal microbiota on gynecological diseases in women. By reviewing recent research, we hope to contribute to the advancement of academic medicine's understanding of the vaginal microbiota's importance in female health. We also aim to raise awareness among healthcare professionals and the general public of the significance of maintaining a healthy vaginal microbiota for better reproductive health and the prevention of gynecological diseases.

Exposure to Di-(2-Ethylhexyl) phthalate drives ovarian dysfunction by inducing granulosa cell pyroptosis via the SLC39A5/NF-κB/NLRP3 axis

Endocrine-disrupting chemicals (EDCs) have been reported to affect populations by disrupting the human endocrine system. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC that is present in various consumer products. Exposure to DEHP could contribute to reproductive system dysfunction, with subsequent adverse female reproductive outcomes. Granulosa cells (GCs) play essential roles in ovarian function and fertility. To further reveal the underlying mechanism by which DEHP impairs female fertility and affects the normal function of GCs, in vivo and in vitro experiments were performed. Transcript sequencing was used to identify genes that were differentially expressed in GCs after DEHP treatment. SLC39A5 was shown to be overexpressed in the DEHP group compared to the normal control group. DEHP treatment and overexpression of SLC39A5 activated NF-κB-related factors, followed by an increase in the transcript expression level of NLRP3. NLRP3 inflammasomes play crucial roles in pyroptosis by acting as sensors. Pyroptosis is a type of inflammation-related cell death associated with various diseases, including ovarian cancer and polycystic ovary syndrome. Activation of NF-κB contributed to the upregulation of pyroptosis in GCs, while pyroptosis factors were downregulated after the inhibition of NF-κB with JSH-23. The same phenomenon was also observed in a mouse model in which DEHP-treated mice had higher expression levels of NF-κB and pyroptosis markers in GCs. Moreover, this phenomenon could be partially reversed by the NF-κB inhibitor JSH-23. DEHP treatment also disrupted the normal expression of ovarian function-related genes and inhibited the proliferation of GCs. Reproductive system impairment was observed in mice exposed to DEHP. DEHP-treated mice had a lower body weight, smaller reproductive organs, fewer healthy follicles, and diminished ovarian reserve. Thus, DEHP contributes to ovarian dysfunction by inducing pyroptosis via the SLC39A5/NF-κB/NLRP3 axis in GCs.

Characterizing the follicular fluid metabolome: quantifying the correlation across follicles and differences with the serum metabolome

To compare the variability in metabolomes between the serum and follicular fluid, as well as across 3 dominant follicles. Prospective cohort study. An academic fertility clinic in the northeastern United States, 2005-2015. One hundred thirty-five women undergoing invitro fertilization treatment who provided a serum sample during ovarian stimulation and up to 3 follicular fluid samples during oocyte retrieval. None. Samples were analyzed using liquid chromatography with high-resolution mass spectrometry and 2 chromatography columns (C18 hydrophobic negative and hydrophilic interaction chromatography [HILIC] positive). We calculated overall, feature-specific, and subject-specific correlation coefficients to describe how strongly the intensity of overlapping metabolic features were associated between the serum and follicular fluid and between the 1st-2nd, 1st-3rd, and 2nd-3rd follicles. Feature-specific correlations were adjusted for age, body mass index, infertility diagnosis, ovarian stimulation protocol, and year. From the C18-negative column and the high-resolution mass spectrometry, 7,830 serum features and 10,790 follicular fluid features were detected in ≥20% of samples. After screening retention times and checking for 1:1 matching, 1,928 features overlapped between the 2 metabolomes. From the HILIC-positive column and the high-resolution mass spectrometry, after applying the same exclusion criteria, there were 9,074 serum features, 5,542 follicular fluid features, and 1,149 features that overlapped. When comparing the feature intensity of overlapping metabolites in the serum and the follicular fluid, the overall (C18, 0.45; HILIC, 0.63), median feature-specific (C18, 0.35; HILIC, 0.37), and median subject-specific (C18, 0.42; HILIC, 0.59) correlations were low to moderate. In contrast, among the overlapping features across all 3 follicles, the overall (C18, all 0.99; HILIC, all 0.99), median feature-specific (C18, 0.74-0.81; HILIC, 0.79-0.85), and median subject-specific (C18, 0.88-0.89; HILIC, 0.90-0.91) correlations between follicular fluid metabolomics features within a woman were high. We observed minimal overlap and weak-to-moderate correlation between metabolomic features in the serum and follicular fluid but a large overlap and strong correlation between metabolomic features across follicles within a woman. The follicular fluid appears to represent a novel matrix, distinct from serum, which may be a rich source of biologic predictors of female fertility and reproductive outcomes.

Effect of Parental Age and Mating Status on Reproductive Performance of Orius laevigatus (Hemiptera: Anthocoridae).

Simple SummaryThe successful function of biological control agents (BCAs) in a crop heavily depends on their reproductive potential, and it all begins at the mating. Reproductive potential is crucial for both the mass-rearing and field performance of natural enemies. The present study aimed to evaluate how many consecutive females of Orius laevigatus a male can mate and the effect on female’s reproductive performance. In addition, we wanted to see the effect of the age of the male and female at mating. In the multiple mating experiment, the males of O. laevigatus showed a high capacity to fertilize females successively, not reducing the fecundity until the sixth mated female. Therefore, the proportion of males in mass rearing could be reduced. In the delayed mating experiment, copulation duration and fecundity increased with the age of the male but decreased with the age of the female. In contrast, fertility (percentage of egg hatching) followed a pattern contrary to fecundity, increasing with female age but decreasing with male age, although it did not counterbalance the advantage granted by higher fecundity. In conclusion, reproductive capacity is increased with very young females and with males a few days old.The reproductive potential of biological control agents (BCAs) is crucial for efficient mass-rearing and field performance, and it all begins with mating. Fecundity can be strongly influenced by intrinsic conditions, such as female age and, often neglected, male age and mating status. However, little is known about the impact of parental status at mating on female reproductive outcomes in BCAs. Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) is widely used to control thrips in protected crops. We evaluated how many consecutive females a male could successfully mate and the effect on a female’s reproductive output. In addition, we studied the effects of male and female age on mating. In the multiple mating experiment, the males showed a high capacity to fertilize females successively, not reducing fecundity until the sixth mated female. In the delayed mating experiment, copulation duration and fecundity increased with male age but decreased with female age. In contrast, fertility followed an opposite pattern, increasing with female age but decreasing with male age. However, fecundity gains outweighed fertility declines in both sexes. Therefore, reproductive capacity is increased when mating newly emerged females with males a few days old. The implications of our results for mass rearing and field performance are discussed.

Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review.

Female infertility is a major public health concern and a global challenge. It is a disorder of the reproductive system, defined as the inability to achieve a clinical pregnancy. Nutrition and other environmental factors are found to impact reproductive health in women as well as the outcome of assisted reproductive technologies (ART). Dietary factors, such as polyunsaturated fatty acids (PUFA), fiber as well as the intake of Mediterranean diet appear to exert beneficial effects on female reproductive outcomes. The exact mechanisms associating diet to female fertility are yet to be identified, although genomic, epigenomic, and microbial pathways may be implicated. This review aims to summarize the current knowledge on the impact of dietary components on female reproduction and ART outcomes, and to discuss the relevant interplay of diet with genome, epigenome and microbial composition.

Effects of Phthalate Mixtures on Ovarian Folliculogenesis and Steroidogenesis.

The female reproductive system is dependent upon the health of the ovaries. The ovaries are responsible for regulating reproduction and endocrine function. Throughout a female’s reproductive lifespan, the ovaries undergo continual structural changes that are crucial for the maturation of ovarian follicles and the production of sex steroid hormones. Phthalates are known to target the ovaries at critical time points and to disrupt normal reproductive function. The US population is constantly exposed to measurable levels of phthalates. Phthalates can also pass placental barriers and affect the developing offspring. Phthalates are frequently prevalent as mixtures; however, most previous studies have focused on the effects of single phthalates on the ovary and female reproduction. Thus, the effects of exposure to phthalate mixtures on ovarian function and the female reproductive system remain unclear. Following a brief introduction to the ovary and its major roles, this review covers what is currently known about the effects of phthalate mixtures on the ovary, focusing primarily on their effects on folliculogenesis and steroidogenesis. Furthermore, this review focuses on the effects of phthalate mixtures on female reproductive outcomes. Finally, this review emphasizes the need for future research on the effects of environmentally relevant phthalate mixtures on the ovary and female reproduction.

Oxidative stress and female reproductive disorder

Oxidative stress arises from an imbalance between the body's pro-oxidants and antioxidants. Recently, oxidative stress has been proven a contributing factor to many female reproductive disorders including infertility, preeclampsia, endometriosis and polycystic ovarian syndrome. Herein, we review the mechanistic role of oxidative stress in inducing the most common female reproductive disorders. The current review has also highlighted the protective role of vitamin C, necessary for certain female reproductive hormone secretion by the antral follicle and corpus luteum and also essential for collagen production in ovarian tissue remodeling after ovulation, in alleviating oxidative stress and thus improving female reproductive outcomes.

Endometrial microbiota composition is associated with reproductive outcome in infertile patients

BackgroundPrevious evidence indicates associations between the female reproductive tract microbiome composition and reproductive outcome in infertile patients undergoing assisted reproduction. We aimed to determine whether the endometrial microbiota composition is associated with reproductive outcomes of live birth, biochemical pregnancy, clinical miscarriage or no pregnancy.MethodsHere, we present a multicentre prospective observational study using 16S rRNA gene sequencing to analyse endometrial fluid and biopsy samples before embryo transfer in a cohort of 342 infertile patients asymptomatic for infection undergoing assisted reproductive treatments.ResultsA dysbiotic endometrial microbiota profile composed of Atopobium, Bifidobacterium, Chryseobacterium, Gardnerella, Haemophilus, Klebsiella, Neisseria, Staphylococcus and Streptococcus was associated with unsuccessful outcomes. In contrast, Lactobacillus was consistently enriched in patients with live birth outcomes.ConclusionsOur findings indicate that endometrial microbiota composition before embryo transfer is a useful biomarker to predict reproductive outcome, offering an opportunity to further improve diagnosis and treatment strategies.4s24pSLHML6tsFwrrAE7giVideo .