Xu Ke, Wang Yunyi, Gao Xiao, Wei Zhaolan, Han Qi, Wang Shuxin, Du Wanting, Wan Jian, Wan Cuihong, Chen Mingqing
School of Life Sciences, Central China Normal University, Wuhan, 430079, Hubei, China.
Environ Sci Ecotechnol. 2024 Aug 3;22:100471. doi: 10.1016/j.ese.2024.100471. eCollection 2024 Nov.
Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats' reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor β1 (TGF-β1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-β1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.
微塑料和邻苯二甲酸盐是普遍存在且新出现的污染物，对人类健康构成潜在影响。先前的研究表明，微塑料和邻苯二甲酸盐都会对人类和哺乳动物的生殖系统产生不利影响。然而，这些污染物对女性生殖系统的综合影响仍不清楚。在此，我们展示了暴露于聚苯乙烯微塑料（PS-MPs）和邻苯二甲酸二（2-乙基己基）酯（DEHP）对雌性斯普拉格-道利大鼠生殖系统的影响。我们发现，PS-MPs和DEHP共同暴露导致大鼠卵巢中囊性和闭锁卵泡显著增加、氧化应激、纤维化以及血清性激素稳态失调。蛋白质组学分析确定了差异表达的蛋白质，这些蛋白质主要富集在与脂肪酸代谢和紧密连接相关的信号通路中，受转化生长因子β1（TGF-β1）调控。我们进一步证实，DEHP和PS-MPs共同暴露会激活TGF-β1/Smad3信号通路，抑制该通路可减轻氧化应激、激素失调和卵巢纤维化。这些结果表明，微塑料和邻苯二甲酸盐的联合暴露会导致闭锁卵泡显著增加，并可能增加多囊卵巢综合征（PCOS）的风险。我们的研究为微塑料和DEHP暴露对雌性哺乳动物的生殖毒性作用提供了新见解，突出了环境污染物与PCOS发生之间的潜在联系。这些发现凸显了全面评估微塑料污染对女性生殖健康风险的必要性，并为评估此类风险提供了科学依据。
