Dysregulation of steroid metabolome in follicular fluid links phthalate exposure to diminished ovarian reserve of childbearing-age women

邻苯二甲酸盐 代谢组 内分泌学 内科学 生物 卵巢储备 卵泡期 生理学 医学 化学 怀孕 不育 遗传学 代谢物 有机化学
作者
Yongcheng Li,Nan Xiao,Min Liu,Yarui Liu,Ana He,Lei Wang,Haining Luo,Yiming Yao,Hongwen Sun
出处
期刊:Environmental Pollution [Elsevier BV]
卷期号:330: 121730-121730 被引量:15
标识
DOI:10.1016/j.envpol.2023.121730
摘要

The widespread use of phthalates (PAEs) has drawn increasing attention due to their endocrine disruption and reproductive toxicity, while the steroid metabolome is essential for follicular development. However, the mechanism by which PAE exposure affects ovarian reserve through the steroid metabolome remains unclear. This study recruited 264 childbearing-age women in Tianjin (China) from April 2019 to August 2020 in a cross-sectional design. Target metabolome analysis of 16 steroids was performed in follicular fluid (FF) to compare diminished ovarian reserve (DOR) against normal ovarian reserve (NOR) women and differential steroids were identified using binary logistic analyses. Further analysis of eleven PAE metabolites (mPAEs) in FF was conducted, and the retrieved oocyte number (RON) representing ovarian reserve was counted. Multiple linear regression and quantile-based g-computation (qgcomp) models were used to associate individual mPAEs and mPAE mixture with the DOR-related differential steroids in FF. Mediation analysis was used to discuss the mediating effect of DOR-related steroids on the association between mPAEs and RON. Androstenedione (A4), corticosterone (CORT), cortisol (COR) and cortisone were significantly down-regulated in FF from women with DOR. Nine mPAEs with detection frequencies greater than 60% and median concentrations of 0.02-4.86 ng/mL were incorporated into statistical models. Negative associations with COR and CORT were found for mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-2-ethylhexyl phthalate (mEHP). A positive association with cortisone was found for mEOHP, mEHP, monobutyl phthalate (mBP), and mono (2-isobutyl) phthalate (miBP). The qgcomp and mediation analyses revealed that mEP and mEOHP not only significantly contributed to the decline of COR and CORT in the mixed exposure but also indirectly reduced RON through the mediating effects of COR and CORT. In conclusion, PAE exposure may decrease ovarian reserve by downregulating COR and CORT.
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