Reproductive toxicology最新文献

Background: In recent years, phthalate plasticizers have been increasingly linked to various male reproductive health issues. However, their relationship with erectile dysfunction (ED) remains insufficiently studied. This study aims to elucidate the molecular mechanisms by which phthalate plasticizers contribute to ED.

Methods: Using a network toxicology approach, we predicted potential molecular targets of three common phthalates-DEHP, DIBP, and DMP-associated with ED through multiple online databases. Next, we integrated transcriptomic datasets from three established ED rat models (diabetic, neurogenic, and hypertensive) to identify more robust and representative candidate genes. Subsequently, LASSO and SVM-RFE machine learning algorithms were employed to screen for key phthalate related ED genes. Molecular docking was then conducted to validate the binding affinity between phthalates and these candidate targets.

Results: Network toxicology analysis identified 101 genes potentially linking phthalates to ED. Enrichment analyses revealed that these genes are primarily involved in endothelial dysfunction, oxidative stress, and cell growth regulation. From the integrated ED transcriptomic dataset, 1002 differentially expressed genes were identified, among which 12 overlapped with the phthalate-ED associated genes. These overlapping genes were closely related to neurodegenerative diseases and metabolic disorders. LASSO and SVM-RFE models further narrowed the list to four key genes: CDKN1B, IDH1, CASR, and PRNP.

Conclusion: The four key genes-CDKN1B, IDH1, CASR, and PRNP-appear to play critical roles in phthalate-induced ED. These genes are potentially involved in mechanisms such as oxidative stress dysregulation, neural injury, and endocrine disorders. Our findings provide important theoretical insights into the pathogenesis and prevention of environmentally induced ED.

Background: Brominated flame retardants (BFRs) are endocrine-disrupting contaminants; however, the impact of BFR mixtures on sex steroid hormone levels in adults remains unclear.

Methods: This study included 2513 male and female adults from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Weighted linear regression was employed to examine the associations between individual BFR exposures and total testosterone(TT), estradiol(E2), sex hormone binding globulin (SHBG), free androgen index (FAI), and TT/E2. The generalized additive model (GAM) was used to explore the nonlinear associations between BFRs and sex steroid hormones. Additionally, weighted quantile sum (WQS) regression and Quantile G-computation (QGC) were applied to evaluate the overall effects of BFRs mixtures on these five sex hormone biomarkers and to identify key contributing chemicals. We also explored potential effect modifications by age, BMI and educational level.

Result: The weighted linear regression results indicated that, after adjusting for covariates, PBDE209 was significantly negatively associated with SHBG in males (β = -8.495, 95 % CI: -15.915, -1.073), while PBB153 and PBDE85 were negatively associated with female TT/E2 (β = -0.718, 95 % CI: -1.362, -0.075) and E2 (β = -2.910, 95 % CI: -5.126, -0.693), respectively. The Generalized Additive Model (GAM) revealed nonlinear associations between certain BFRs and TT, E2, FAI, and TT/E2 in both males and females. WQS regression analysis showed a significant negative association between the WQS index and male SHBG (β = -1.919, 95 % CI: -3.706, -0.133), which was consistent with the results from the weighted linear regression. However, no significant associations were observed between mixed BFR exposure and female sex hormone levels. Further confirmation of the WQS regression findings was provided by QGC analysis. Notably, PBDE209 was identified as the primary BFR influencing SHBG levels.

Conclusion: Exposure to mixed BFRs significantly affects SHBG levels in adult males, while no significant impact on sex steroid hormone levels was observed in adult females. Further studies are required to evaluate the potential long-term health consequences.

The pervasive environmental contamination by microplastics (MPs) has emerged as a significant threat to human health, with mounting evidence linking exposure to gynecological tumors. This comprehensive review synthesizes current scientific evidence by examining the established risks of chemical additives, exploring the carcinogenic mechanisms of the particles themselves, and highlighting the recent direct detection of MPs in human gynecological tissues. Evidence for this association is multi-faceted: plastic additives such as phthalates and bisphenol A (BPA) are epidemiologically linked to increased cancer risk, while the MP particles themselves are shown to induce pro-carcinogenic responses including oxidative stress, chronic inflammation, and epigenetic changes. Critically, recent studies now confirm the physical presence of MPs within human gynecological tumor tissues, often at higher concentrations than in adjacent normal tissue, strengthening the clinical relevance of these findings. The convergence of chemical, mechanistic, and clinical evidence establishes a compelling case for MP exposure as an emerging risk factor for gynecological malignancies. The findings underscore an urgent need for further research, standardized detection methodologies, and public health strategies to mitigate this environmental threat.

Background: Prenatal exposure to phthalates is reported to influence fetal growth and may lead to lasting adverse effects on infants and their future development; yet, the results remain inconclusive.

Objective: This study utilized a birth cohort of 73 pregnant women-newborn pairs, including biological fathers (73 triads), to investigate the relationship between parental phthalate exposure during pregnancy and birth outcomes in newborns.

Methods: Demographic, behavioral, and clinical information, along with urine samples from both parents, were collected prior to delivery. Sixteen phthalate metabolites were quantified in urine samples.

Results: Significant correlations were observed between six phthalate metabolites (MEP, MiBP, MnBP, MBzP, MEHP, and 5cx-MEPP) in maternal urine and paternal levels. Maternal MBzP was positively associated with boys' birth weight, whereas maternal 2cx-MMHP was negatively associated with girls' birth weight. The ponderal index of boys was negatively related to maternal MBzP and MMP, but positively associated with ∑MEHP-3 and ∑MEHP-5 after adjusting for confounding variables. Among paternal phthalates, MBzP showed a negative association with boys' ponderal index, whereas MEP showed a positive association. Maternal MEOHP, ∑MEHP-3, and ∑MEHP-5 were positively associated with boys' placenta weight, while MEOHP, MEHHP, 5cx-MEPP, ∑MEHP-3, and ∑MEHP-5 were negatively associated with girls' placenta weight.

Conclusions: Our findings suggest that parental exposure to phthalates at birth may adversely affect fetal growth and placental development in neonates. However, further studies with larger sample sizes and datasets are necessary.

3-Nitropropionic acid (3-NP), a mycotoxin present in various plants and fungi, poses significant reproductive health risks to animals and humans through food chains contamination. This study aimed to explore the protective effects and mechanisms of silibinin, a bioactive flavonoid derived from the herbal plant Silybum marianum, against 3-NP-induced reproductive toxicity. Our findings demonstrated that silibinin treatment significantly alleviated 3-NP-induced ovarian follicular atresia and preserved ovarian histoarchitecture. Furthermore, it attenuated oxidative stress induced by 3-NP. Molecular analyses through qPCR and Western blot revealed that silibinin upregulated Bax and Caspase-3 expressions while downregulating Bcl-2 expression in the ovaries compared to the 3-NP group. Immunohistochemistry analysis of CASPASE-3 demonstrated that silibinin significantly inhibited 3-NP-induced apoptosis, predominantly in granulosa cells. Additionally, Western blot analyses showed that silibinin suppressed 3-NP-induced activation of JNK and ERK phosphorylation, downregulated KEAP1 expression, and upregulated NRF2 nuclear translocation in the ovary. Overall, our results indicate that silibinin effectively alleviated 3-NP-induced ovarian oxidative damage by modulating the JNK/ERK signaling pathways and activating the KEAP1/NRF2 signaling pathway. These findings suggest that silibinin may have potential therapeutic application for mitigating 3-NP-induced reproductive toxicity in animal husbandry and the veterinary industry.

Phthalate metabolites Mono- (2-ethylhexyl) phthalate(MEHP) and Phthalic Acid Monobenzyl Ester (MBZP) are widely present in the environment, can interfere with the endocrine system and accumulate in human tissues, and are closely related to the occurrence and development of endometriosis. In this study, by integrating multiple databases such as ChEMBL and STITCH, 503 human target genes of the two metabolites were screened out. After intersection with 1735 genes related to endometriosis, a core gene set of 50 was obtained. GO and KEGG enrichment analyses revealed that these genes were mainly involved in pathways such as arachidonic acid metabolism, IL-17 signaling pathway, cell burial, and complement-coagulation cascade reaction, and were involved in the processes of survival, migration, and fibrotic remodeling of ectopic endometrial cells driven by oxidative stress. Through the construction of PPI networks and the validation of machine learning models, ACE, MMP2, PPARG and SERPINE1 were identified as key hub proteins.The diagnostic ability AUC of each single gene reaches 0.80.Molecular docking experiments confirmed that MEHP and MBZP have high affinity (ΔG - 8.5 to - 6.3 kcal/mol) for the above-mentioned proteins, providing atomic-level evidence for their molecular regulatory mechanisms. This study systematically elucidated the multi-level mechanisms of endometriosis caused by phthalate exposure and proposed a precise diagnostic strategy based on core genes, providing new ideas for the prevention and targeted treatment of diseases related to environmental pollutants.