Female Reproductive Disorders Research Articles

Ferroptosis: First evidence in premature duck ovary induced by polyvinyl chloride microplastics

Ferroptosis is frequently observed in fibrosis and diseases related to iron metabolism disorders in various mammalian organs. However, research regarding the damage mechanism of ferroptosis in the female reproductive system of avian species remains unclear. In this study, Muscovy female ducks were divided into three groups which were given purified water, 1 mg/L polyvinyl chloride microplastics (PVC-MPs) and 10 mg/L PVC-MPs for two months respectively, to investigate the ferroptosis induced by PVC-MPs caused ovarian tissue fibrosis that lead to premature ovarian failure. The results showed that the high accumulation of PVC-MPs in ovarian tissue affected the morphology and functional activity of ovarian granulosa cells (GCs) and subsequently caused the follicular development disorders and down-regulated the immunosignaling of ovarian steroidogenesis proteins 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), CYP11A1 cytochrome (P450-11A1) and CYP17A1 cytochrome (P450-17A1) suggested impaired ovarian function. In addition, PVC-MPs significantly up-regulated positive expression of collagen fibers, significantly increased lipid peroxidation and malondialdehyde (MDA) level, along with encouraged overload of iron contents in the ovarian tissue were the characteristics of ferroptosis. Further, immunohistochemistry results confirmed that immunosignaling of ferroptosis related proteins Acyl-CoA synthetase (ACSL4), Cyclooxygenase 2 (COX2) and ferritin heavy chain 1 (FTH1) were significantly increased, but solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase (GPX4) were decreased by PVC-MPs in the ovarian tissue. In conclusion, our study demonstrates that PVC-MPs induced ferroptosis in the ovarian GCs, leading to follicle development disorders and ovarian tissue fibrosis, and ultimately contributing to various female reproductive disorders through regulating the proteins expression of ferroptosis.

Betaine Attenuates The Expression of Vasoactive Mediators and Histological Alterations Associated with Ovarian Hyperstimulation Syndrome in Rats.

Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur after administration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule with anti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model of OHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictor proteins and ovarian histological changes in an experimental OHSS rat model. In this experimental study, 30 adult female rats (two months old) were randomly divided into six groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by 30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days), iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone (P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes. Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atretic follicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of the VEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantly attenuated all molecular and histological alterations observed in the OHSS animals. Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patients by reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings are similar to CAB and can be a new avenue for future research on BET.

Ovarian PERK/NRF2/CX43/StAR/progesterone pathway activation mediates female reproductive dysfunction induced by cold exposure

Ambient air temperature is a key factor affecting human health. Female reproductive disorders are representative health risk events under low temperature. However, the mechanism involving in cold-induced female reproductive disorders remains largely unknown. Female mice were intermittently exposed to cold conditions (4 °C) to address the health risk of low temperature on female reproductive system. Primary granulosa cells (GCs) were prepared and cultured under low temperature (35 °C) or exposed to β3-adrenoreceptor agonist, isoproterenol, to mimic the condition of cold exposure. Western-blot, RT-PCR, co-IP, ELISA, pharmacological inhibition or siRNA-mediated knockdown of target gene were performed to investigate the possible role of hormones, gap conjunction proteins, and ER stress sensor protein in regulating female reproductive disorders under cold exposure. Cold exposure induced estrous cycle disorder and follicular dysplasia in female mice, accompanying with abnormal upregulation of progesterone and its synthetic rate-limiting enzyme, StAR, in the ovarian granulosa cells. Under the same conditions, an increase in connexin 43 (CX43) expressions in the GCs was also observed, which contributed to elevated progesterone levels in the ovary. Moreover, ER stress sensor protein, PERK, was activated in the ovarian GCs after cold exposure, leading to the upregulation of downstream NRF2-dependent CX43 transcription and aberrant increase in progesterone synthesis. Most importantly, blocking PERK expression in vivo significantly inhibited NRF2/CX43/StAR/progesterone pathway activation in the ovary and efficiently rescued the prolongation of estrous cycle and the increase in follicular atresia of the female mice induced by cold stress. We have elucidated the mechanism of ovarian PERK/NRF2/CX43/StAR/progesterone pathway activation in mediating female reproductive disorder under cold exposure. Targeting PERK might be helpful for maintaining female reproductive health under cold conditions.

Predicting nutrition and environmental factors associated with female reproductive disorders using a knowledge graph and random forests

ObjectiveFemale reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (for example, endometriosis, ovarian cyst, and uterine fibroids). Materials and MethodsWe harmonized survey data from the Personalized Environment and Genes Study (PEGS) on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and applying a random forest for edge prediction to identify variables potentially associated with FRDs. We also conducted logistic regression analysis for comparison. ResultsAcross 9765 PEGS respondents, the KG analysis resulted in 8535 significant or suggestive predicted links between FRDs and chemicals, phenotypes, and diseases. Amongst these links, 32 were exact matches when compared with the logistic regression results, including comorbidities, medications, foods, and occupational exposures. DiscussionMechanistic underpinnings of predicted links documented in the literature may support some of our findings. Our KG methods are useful for predicting possible associations in large, survey-based datasets with added information on directionality and magnitude of effect from logistic regression. These results should not be construed as causal but can support hypothesis generation. ConclusionThis investigation enabled the generation of hypotheses on a variety of potential links between FRDs and exposures. Future investigations should prospectively evaluate the variables hypothesized to impact FRDs.

Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

Abstract 4650: RalBP1, a novel approach for ovarian cancer therapy

Abstract Ovarian cancer (OC) is the most devastating gynecologic cancer. The ever-climbing incidence rate of OC makes it the most lethal female reproductive disorder. Triggering apoptosis is one of the potential strategies to overcome chemoresistance. Recent evidence suggests that the failure of drug-induced apoptosis may be an underlying cause of drug-resistance. Molecular mechanisms of failed apoptosis in chemoresistant OC cells include p53 mutations, abnormal expression of the Bcl2 family proteins, and upregulation of other inhibitors of apoptosis that block caspases and stabilize the mitochondrial permeability pore. RalBP1 (Ral-binding protein) is a required stress-defense protein for OC, and its specific depletion or inhibition will cause apoptosis in cancer cells expressing RalBP1. RalBP1 is a multifunctional 76 kDa protein encoded as a splice variant in the human RALBP1 gene (18p11.22). RalBP1 is an ATP dependent efflux transporter for glutathione (GSH) conjugates (GS-E) of products of oxidative stress, like 4HNE and GSH-conjugates of chemotherapy drugs. Our recent studies indicate that upon depletion/inhibition of RalBP1, malignant cells are significantly more sensitive to apoptosis than non-malignant cells, suggesting that the stress-protective, anti-apoptotic activity of RalBP1 is necessary for malignant cells. This differential sensitivity to RalBP1 translates into tumor regression, a lack of toxicity, and the prolonged survival of mice bearing subcutaneous OC cells in which RalBP1 is inhibited by anti-RalBP1 IgG or depleted using RalBP1 antisense oligonucleotides. These studies demonstrate that inhibition or depletion of RalBP1 exerts anti-neoplastic effects in OC and indicate that this GS-E and xenobiotic transporter occupies an important position in the hierarchy of stress defense mechanisms necessary for cancer cell survival. Overall, the present research focuses on hypothesis-driven studies to define novel relationships between RalBP1 and signaling pathways, and to determine the suitability of RalBP1 as an anticancer target for OC. Citation Format: Sharad S. Singhal, Sravani Ramisetty, Atish Mohanty, Prakash Kulkarni, David Horne, Sanjay Awasthi, Ravi Salgia. RalBP1, a novel approach for ovarian cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4650.

Levels of Phthalate Acid Esters in Carbonated Soft Drinks Bottled in Polyethylene Terephthalate (PET) Bottles Kept under Various Storage Conditions in Mwanza City, Tanzania

Background: Carbonated soft drinks (CSD), packaged in PET (polyethylene terephthalate) bottles, are among the most widely consumed non-alcoholic beverage globally. People of all ages enjoy CSDs for their flavour, mouthfeel, crispness, freshness, and capacity to both quench thirst and provide mental refreshment. Terephthalic acid, ethylene glycol, and other additives such as phthalates are the materials used to make these PET bottles. Several studies have demonstrated that phthalates may migrate into packaged goods and, when consumed, can cause several ill-health conditions to humans. Type II diabetes, obesity, asthma, male and female reproductive disorders, tumours (including breast cancer), pituitary, hypothalamic, and peripheral hormone disorders, behavioral issues, and neurodevelopmental disorders are among the health issues reported to be associated with phthalates. Objective: This study aimed to ascertain the presence and concentration of phthalates in PET bottled carbonated soft drinks produced in Mwanza City, and to examine the effects of various storage conditions on the migration of these contaminants into the product. Methods: Liquid-liquid extraction, clean-up techniques, and chromatographic analysis were used as the methods of determination to identify and quantify the specific phthalates compounds. Results: The findings demonstrated that after being stored outdoors for four to six months, the migration, especially for dibutyl phthalate (DBP) and di [2-ethylhexyl] phthalate (DEHP), became more apparent. After two, four, and six months of indoor storage, there was no appreciable change in the mean concentrations of DMP (dimethyl phthalate), DEP (diethyl phthalate), DBP (dibutyl phthalate), and DEHP for either brand in this study. Compared to indoor storage, the DBP and DEHP migration increased by up to 24-fold when the two brands were kept outdoors for four and six months. Thus, the safety and quality of carbonated soft drinks were seriously compromised by the phthalate compounds from the PET bottles that these companies were using. Conclusion: The study's conclusions show that PET packaging, which is influenced by the bottle manufacturing process and raw material formulations for packages of the studied CSDs, are responsible for the migration of phthalates into the products. The storage conditions and time are established to be the primary causes of phthalates migration in bottled carbonated soft drinks. Though the migration figures in this study are lower than those of the other studies from different locations that were compared, it is important to remember that these compounds may interfere with hormones even in small quantities.

Epidemiologic and genetic associations of female reproductive disorders with depression or dysthymia: a Mendelian randomization study

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer. We analyzed a substantial sample size, ranging from 111,831 to 210,870 individuals, and employed robust statistical methods, including inverse variance weighted, MR-Egger, weighted median, and MR-PRESSO, to estimate causal effects. Sensitivity analyses, such as Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots, were also conducted to ensure the validity of our results. Furthermore, risk factor analyses were performed to investigate potential mediators associated with these observed relationships. Our results demonstrated that genetic predisposition to depression or dysthymia was associated with an increased risk of developing PCOS (OR = 1.43, 95% CI 1.28–1.59; P = 6.66 × 10–11), ovarian cysts (OR = 1.36, 95% CI 1.20–1.55; P = 1.57 × 10–6), AUB (OR = 1.41, 95% CI 1.20–1.66; P = 3.01 × 10–5), and endometriosis (OR = 1.43, 95% CI 1.27–1.70; P = 2.21 × 10–7) after Bonferroni correction, but no evidence for reverse causality. Our study did not find any evidence supporting a causal or reverse causal relationship between depression/dysthymia and other types of female reproductive disorders. In summary, our study provides evidence for a causal relationship between genetically predicted depression and specific types of female reproductive disorders. Our findings emphasize the importance of depression management in the prevention and treatment of female reproductive disorders, notably including PCOS, ovarian cysts, AUB, and endometriosis.

The role of the annexin A protein family at the maternal-fetal interface.

Successful pregnancy requires the tolerance of the maternal immune system for the semi-allogeneic embryo, as well as a synchrony between the receptive endometrium and the competent embryo. The annexin family belongs to calcium-regulated phospholipid-binding protein, which functions as a membrane skeleton to stabilize the lipid bilayer and participate in various biological processes in humans. There is an abundance of the annexin family at the maternal-fetal interface, and it exerts a crucial role in embryo implantation and the subsequent development of the placenta. Altered expression of the annexin family and dysfunction of annexin proteins or polymorphisms of the ANXA gene are involved in a range of pregnancy complications. In this review, we summarize the current knowledge of the annexin A protein family at the maternal-fetal interface and its association with female reproductive disorders, suggesting the use of ANXA as the potential therapeutic target in the clinical diagnosis and treatment of pregnancy complications.

The Potential of Tissue Engineering in Treatment of Female Reproductive System Disorders: A Review

The Potential of Tissue Engineering in Treatment of Female Reproductive System Disorders: A Review

Ayurvedic Management of Unexplained Secondary Infertility – a Case Study

Introduction: Secondary infertility indicates previous pregnancy but failure to conceive subsequently. Incidences of secondary infertility are increasing day by day. Many factors like age, hectic schedule, stress, diet, unhealthy lifestyle are responsible for it. Psychological stress disturbs overall health of women by inducing generation of reactive oxygen species and thereby oxidative stress. This oxidative stress may hamper the health of ovaries, oocyte quality and causes female reproductive health disorders. Aim: To study the effect of Ayurvedic treatment in management of unexplained secondary infertility. Objective: To assess the effect of Ayurvedic management of unexplained secondary infertility. Methodology: Single case study of unexplained secondary infertility. Case description: A 37 years old female patient came in ITRA OPD of Streeroga and Prasutitantra, trying to conceive since 1.5 years. She had a history of 2 MTPs and 1 female child of 10 year. Her last MTP was done in 2020. After that she was actively trying to conceive around last 1.5 years but couldn’t conceive again inspite of regular unprotected coitus. Treatment: She was treated with Ayurvedic oral medications along with Panchakarma. Result: After four months of treatment she conceived and followed Garbhini Paricharya. Conclusion: Ayurvedic management can act as an anti-stress and antioxidant agent thereby improving the reproductive health of women and increasing their chances of conception.

Potential Causal Association between Plasma Metabolites, Immunophenotypes, and Female Reproductive Disorders: A Two-Sample Mendelian Randomization Analysis.

While extensive research highlighted the involvement of metabolism and immune cells in female reproductive diseases, causality remains unestablished. Instrumental variables for 486 circulating metabolites (N = 7824) and 731 immunophenotypes (N = 3757) were derived from a genome-wide association study (GWAS) meta-analysis. FinnGen contributed data on 14 female reproductive disorders. A bidirectional two-sample Mendelian randomization study was performed to determine the relationships between exposures and outcomes. The robustness of results, potential heterogeneity, and horizontal pleiotropy were examined through sensitivity analysis. High levels of mannose were found to be causally associated with increased risks of gestational diabetes (GDM) (OR [95% CI], 6.02 [2.85-12.73], p = 2.55 × 10-6). A genetically predicted elevation in the relative count of circulating CD28-CD25++CD8+ T cells was causally related to increased female infertility risk (OR [95% CI], 1.26 [1.14-1.40], p = 1.07 × 10-5), whereas a high absolute count of NKT cells reduced the risk of ectopic pregnancy (OR [95% CI], 0.87 [0.82-0.93], p = 5.94 × 10-6). These results remained consistent in sensitivity analyses. Our study supports mannose as a promising GDM biomarker and intervention target by integrating metabolomics and genomics.

Structural basis of the subcortical maternal complex and its implications in reproductive disorders.

The subcortical maternal complex (SCMC) plays a crucial role in early embryonic development. Malfunction of SCMC leads to reproductive diseases in women. However, the molecular function and assembly basis for SCMC remain elusive. Here we reconstituted mouse SCMC and solved the structure at atomic resolution using single-particle cryo-electron microscopy. The core complex of SCMC was formed by MATER, TLE6 and FLOPED, and MATER embraced TLE6 and FLOPED via its NACHT and LRR domains. Two core complexes further dimerize through interactions between two LRR domains of MATERs in vitro. FILIA integrates into SCMC by interacting with the carboxyl-terminal region of FLOPED. Zygotes from mice with Floped C-terminus truncation showed delayed development and resembled the phenotype of zygotes from Filia knockout mice. More importantly, the assembly of mouse SCMC was affected by corresponding clinical variants associated with female reproductive diseases and corresponded with a prediction based on the mouse SCMC structure. Our study paves the way for further investigations on SCMC functions during mammalian preimplantation embryonic development and reveals underlying causes of female reproductive diseases related to SCMC mutations, providing a new strategy for the diagnosis of female reproductive disorders.

Utility of homoeopathic medicine sepia in female reproductive disorders with it’s reportorial approach

Utility of homoeopathic medicine sepia in female reproductive disorders with it’s reportorial approach

Aberrant CD8+T cells drive reproductive dysfunction in female mice with elevated IFN-γ levels.

Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive. Here, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation. Our findings reveal that heightened IFN-γ levels triggered the infiltration of CD8+T cells in the pituitary gland and female reproductive tract (FRT), resulting in prolactin deficiency and subsequent infertility. Furthermore, we demonstrate that chronic IFN-γ elevation increases effector memory CD8+T cells in the murine ovary and uterus. These insights broaden our understanding of the role of elevated IFN-γ in female reproductive dysfunction and suggest CD8+T cells as potential immunotherapeutic targets in female reproductive disorders associated with chronic systemic IFN-γ elevation.

Invisible Hand behind Female Reproductive Disorders: Bisphenols, Recent Evidence and Future Perspectives.

Reproductive disorders are considered a global health problem influenced by physiological, genetic, environmental, and lifestyle factors. The increased exposure to bisphenols, a chemical used in large quantities for the production of polycarbonate plastics, has raised concerns regarding health risks in humans, particularly their endocrine-disrupting effects on female reproductive health. To provide a basis for future research on environmental interference and reproductive health, we reviewed relevant studies on the exposure patterns and levels of bisphenols in environmental matrices and humans (including susceptible populations such as pregnant women and children). In addition, we focused on in vivo, in vitro, and epidemiological studies evaluating the effects of bisphenols on the female reproductive system (the uterus, ovaries, fallopian tubes, and vagina). The results indicate that bisphenols cause structural and functional damage to the female reproductive system by interfering with hormones; activating receptors; inducing oxidative stress, DNA damage, and carcinogenesis; and triggering epigenetic changes, with the damaging effects being intergenerational. Epidemiological studies support the association between bisphenols and diseases such as cancer of the female reproductive system, reproductive dysfunction, and miscarriage, which may negatively affect the establishment and maintenance of pregnancy. Altogether, this review provides a reference for assessing the adverse effects of bisphenols on female reproductive health.

A metabolomics approach for the evaluation of Ficus benghalensis female in vivo reproductive effects relative to its metabolite fingerprint as determined via UPLC-MS and GC-MS

Ethnopharmacological relevanceFicus benghalensis, commonly known as Banyan Fig, is the national tree of India and its aerial roots are used traditionally to treat female reproductive disorders. However, despite this traditional use, no pharmacological evidence could be traced supporting this use. Additionally, no comprehensive metabolite profiling was reported for F. benghalensis aerial roots. Aim of the studyThis study attempts to justify biochemically the traditional use of F. benghalensis aerial roots in treatment of female reproductive disorders and in relation to its secondary metabolite profile. Materials and methodsTotal ethanol extract (TEE) and subfractions [petroleum ether (PEF), chloroform (CHF), ethyl acetate (EAF) and n-butanol (BUF] were prepared from air-dried powdered aerial roots of F. benghalensis. Detailed in-vivo investigation of the hormonal activity and action mechanism of the total ethanol extract and subfractions was carried out through evaluation of estrogenic and gonadotropic activities. The estrogenic activity was evaluated on ovariectomized immature female rats through estimating uterine weight, vaginal cornification and serum estradiol level along with histological examination of uteri. The gonadotropic activity was measured by assay of follicle stimulating hormone (FSH) and luteinizing hormone (LH) like activities. Total follicular and corpora lutea counts in immature female rats were used to determine FSH and LH like activities, respectively in addition to histological picture of the genitalia. Comprehensive non-targeted metabolite profiling was carried out for the TEE and subfractions using UPLC-HRMS in negative and positive ionization modes. UPLC-MS fingerprint was subjected to principal component analysis (PCA) and partial least squares analyses to correlate the bioactivities to specific chemical constituents in F. benghalensis different subfractions. GC-MS was further used for non-polar silylated fractions. ResultsResults revealed that only the non-polar PEF and CHF displayed moderate estrogenic and FSH-like activities but with no LH-like activity. Metabolites profiling via (UPLC-HRMS) and multivariate PCA analysis enabled identification and comparison of various chemical classes in F. benghalensis extract and fractions. The active non-polar fractions revealed nearly similar metabolites profile being composed of isoflavonoids, triterpenes, sterols, fatty acids and cyclic peptides. In contrast, polar fractions were more abundant in apocarotenoids, fatty acyl amides, hydroxybenzoates and hydroxycinnamates in addition to two lignans. PLS analysis revealed strong correlation between hydroxylated fatty acids and pyranoisoflavones with estrogenic and FSH-like activities. GC-MS analysis was further employed for non-polar fractions profiling revealing for their enrichment in fatty acids/esters, terpenes, organic acids and phenolics. ConclusionThis is the first study to rationalize the use of F. benghalensis aerial root traditionally in treatment of gynecological disorders, revealing that the petroleum ether and chloroform non-polar subfractions of F. benghalensis showed estrogenic and FSH-like activity with absence of LH-like activity. This biological activity could possibly be attributed to its metabolites profile of isoflavonoids, fatty acids, triterpenes, sterols and cyclic peptides identified via UPLC-MS and GC-MS techniques. Consequently, F. benghalensis aerial roots should be used with caution in traditional treatment of female infertility or other reproductive disorders.

Impact of Nutrition on Female Reproductive Disorders

The female reproductive system is a delicate and complex system in the body that can be affected by many disorders [...]

Recurrent human 16p11.2 microdeletions in type I Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients in Chinese Han population.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a severe congenital malformation of the female genital tract, is a highly heterogeneous disease which has no clear etiology. Previous studies have suggested that copy number variations (CNVs) and single-gene mutations might contribute to the development of MRKH syndrome. In particular, deletions in 16p11.2, which are suggested to be involved in several congenital diseases, have been reported in Chinese type II MRKH patients and European MRKH patients. However, few CNVs including 16p11.2 microdeletions were identified in Chinese type I MRKH cases although it accounted for the majority of MRKH patients in China. Thus, we conducted a retrospective study to identify whether CNVs at human chromosome 16p11.2 are risk factors of type I MRKH syndrome in the Chinese Han population. We recruited 143 patients diagnosed with type I MRKH between 2012 and 2014. Five hundred unrelated Chinese without congenital malformation were enrolled in control group, consisting of 197 from the 1000 Genomes Project and 303 from Fudan University. Quantitative PCR, array comparative genomic hybridization, and sanger sequencing were conducted to screen and verify candidate variant. Our study identified recurrent 16p11.2 microdeletions of approximately 600 kb in two out of the 143 type I MRKH syndrome patients using high-density array-based comparative genomic hybridization (aCGH), while no 16p11.2 deletion was found in the control group. We did not find any mutations in TBX6 gene in our samples. The results of the study identify 16p11.2 deletion in Chinese MRKH I patients for the first time, as well as support the contention that 16p11.2 microdeletions are associated with MRKH syndrome in both types across populations. It is suggested that 16p11.2 microdeletions should be included in molecular diagnosis and genetic counseling of female reproductive tract disorders.

Predicting chemicals' toxicity pathway of female reproductive disorders using AOP7 and deep neural networks.

Experimental evidence shows that certain chemicals, particularly endocrine disrupting chemicals, may negatively affect the female reproductive system, thereby lowering women's fertility. However, humans are constantly exposed to a number of different chemicals with limited or no experimental data regarding their effect and the mechanism of action in the female reproductive system. To predict chemical hazards to the female reproductive system, we used a previously defined adverse outcome pathway (AOP) that links activation of the peroxisome proliferator-activated receptor γ to the reproductive toxicity in adult females (AOP7) and the Convolutional Deep Neural Network models that produce meaningful predictions when trained on a significant amount of data. The models trained using CompTox assays with intended molecular and biological targets corresponding to AOP7 achieved high performance (over 90% validation accuracy). The integration of AOP7 and Deep Neural Network identified chemicals that could negatively affect female reproduction through the mechanism described in AOP7. We provide a solution to quickly analyze the data and produce machine learning models to identify potentially active chemicals in the female reproductive system. Although we focused on the female reproductive system, this approach could be valid for a number of other chemicals and AOPs if the right data exist.