In modern society, the progression of ovarian aging in women has accelerated, and the incidence of infertility has increased markedly with a distinct younger-onset trend. Exploring the etiology and pathogenesis of infertility has become a core research focus for clinicians. Plastic products bring tremendous convenience to modern life, while the health risks caused by plastic pollution have aroused global concern. As typical endocrine-disrupting chemicals, microplastics (MPs) can enter the human body through dietary intake, respiration, and skin contact, and accumulate in multiple organs. Accumulated MPs impair the physiological function of the female reproductive system and are closely associated with multiple gynecological disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian insufficiency. After internalization, MPs trigger a series of pathological events such as epigenetic alterations, hormonal metabolism disturbance, inflammatory response, immune dysregulation, oxidative stress, and cellular damage, ultimately resulting in female reproductive impairment. The exposure routes and pathogenic mechanisms underlying MPs-induced reproductive toxicity have emerged as critical scientific issues that urgently require addressing. From an innovative perspective, this review elaborates on the mechanisms underlying the occurrence and progression of female infertility-related diseases mediated by MPs. It aims to provide novel insights for the clinical diagnosis and treatment of female infertility, offer theoretical references for pre-pregnancy counseling and reproductive health management, and supply scientific evidence for the precise prevention and control of MP pollution.

The developing female reproductive tract is highly sensitive to external hormonal stimulation, which can result in infertility and gynecologic diseases. To determine the underlying mechanisms, we used a mouse model to test the direct, cell type-specific effects of neonatal exposure to the estrogenic chemical, diethylstilbestrol (DES), on the developing uterus. We found that control uterine epithelium is in a partial epithelial-mesenchymal transition state that is lost following DES exposure. This is accompanied by evidence of premature differentiation including altered apical-basal cell polarity and absence of the Lgr5+ epithelial stem cell population required for uterine gland formation. Cell-cell communication between epithelial and mesenchymal cells is restructured, and Wnt signaling is aberrantly activated in the epithelium. The DES-exposed uterine mesenchyme has early signs of fibrosis through increased deposition of extracellular matrix (ECM) collagen. Mechanistically, DES exposure causes cell type-specific changes in chromatin accessibility and gene expression, most prominently in epithelial cells. These changes can be explained in part by cell-specific alterations in chromatin looping at enhancer regions in concert with alterations in ERα binding. These findings suggest that reprogramming cell type-specific differentiation trajectories and ECM characteristics underlie the long-term phenotypic effects of developmental exposure to DES and possibly other estrogenic endocrine disrupting chemicals. These changes lead to functional impairment of adult tissues and increased cancer risk.

This study aimed to assess anxiety levels and marital relationships among women undergoing infertility treatment. A descriptive observational design was conducted involving 300 infertile women over nine months at Zagazig University Hospital. Data were collected using a Structured Interview Questionnaire, the Female Sexual Function Index (FSFI), and the Taylor Anxiety Scale. Reliability analysis showed high internal consistency (Cronbach's alpha: 0.923 for FSFI; 0.845 for Taylor Scale). Results indicated that 32.6% of participants sought services after one year of marriage, 30.5% visited more than five centers, and 47.5% used IVF. Nearly half of the subjects experienced varying degrees of anxiety (moderate to very severe), which significantly impacted sexual arousal, orgasm, and satisfaction. In conclusion, anxiety and psychosexual dysfunction are highly prevalent among women during fertility treatments, underscoring the critical need to integrate psychological counseling and standardized screening protocols within routine reproductive healthcare.

Triphenyl phosphate (TPHP), an organophosphorus flame retardant, has emerged as a significant environmental concern due to its persistence and potential health hazards. However, its role in female reproductive toxicity remains poorly understood, necessitating systematic evaluation of its molecular mechanisms. This study integrated network toxicology, transcriptomics, machine learning, adverse outcome pathway (AOP) framework, molecular docking, and in vitro experiments to systematically investigate TPHP-induced reproductive toxicity. Network analysis identified 24 TPHP-infertility shared targets and seven hub genes (AR, CYP19A1, ESR1, ESR2, IGF1, INS, STAR) linked to steroidogenesis and estrogen signalling. Transcriptomic analysis of TPHP-treated KGN cells (GSE241995) revealed downregulated oocyte maturation pathways. Machine learning prioritized ESR1 as the core gene, supported by exploratory external evaluation (AUC = 0.94) in an endometrial dataset (GSE272778). Based on ESR1 prioritization, suppression of estrogen receptor activity was defined as the molecular initiating event (MIE), linking TPHP exposure to downstream STAR suppression, reduced mitochondrial cholesterol transport, impaired progesterone synthesis, and disrupted oocyte maturation. Molecular docking supported the plausibility of TPHP-induced ER activity perturbation. In vitro experiments showed that TPHP significantly suppressed STAR protein expression and progesterone secretion at non-cytotoxic concentrations, whereas total ESR1 protein abundance was not significantly reduced. ESR1 knockdown reduced STAR expression and progesterone production, and TPHP caused no further suppression, supporting an ESR1-related, STAR-dependent mechanism. These findings provide a machine learning-assisted AOP framework and identify ESR1-related steroidogenic disruption as a plausible mechanism of TPHP-induced female reproductive toxicity.

ObjectiveEndometriosis is a systemic chronic disease with serious effects on various aspects of female health and wellbeing that has been associated with a significant increase in free circulating DNA (CfDNA) and gene methylation profile changes. Endometriosis is considered a worldwide health problem, affecting approximately 10-12% of women of reproductive age. It is defined as an estrogen-dependent syndrome associated with severe pain and a distinct epigenetic signature. The purpose of this study was to evaluate the effect of deoxyribonuclease (DNase) I therapy on these anomalies.MethodsThis study is a proof-of-concept investigation presenting preliminary data from sixteen patients with endometriosis who were evaluated during infertility consultations. CfDNA extraction, quantification and methylation status tests were performed using commercial kits. DNase I was administered subcutaneously every 2 days for one month, and the pre-treatment and post-treatment CfDNA levels and methylation status, along with the degree of patient discomfort, were compared.ResultsDNase I therapy was associated with a decrease in the overall CfDNA level. Targeted methylation profiles showed exploratory changes in several genes, presented descriptively because no paired inferential reanalysis was performed. Moreover, most patients (15/16) reported a reduction in pain, an improvement in their ability to assume professional activity and fewer sexual function difficulties.ConclusionsThis proof-of-concept study suggests that DNase I therapy may be associated with decreased CfDNA levels and changes in methylation profiles. Patient-reported improvements in pain and quality of life were observed, but they cannot be causally attributed to treatment in the absence of a placebo-controlled design. Further research into the potential use of DNase-based medicine for endometriosis patients involving more participants is warranted.