Bisphenol A Alternatives in Follicular Fluid: Novel Risk Factors for Ovarian Reserve Dysfunction

Area of Science:

• Endocrinology and Reproductive Biology
• Environmental Health Sciences
• Analytical Chemistry

Background:

• Bisphenol A (BPA), an endocrine-disrupting chemical, is found in follicular fluid and linked to ovarian reserve dysfunction.
• Limited data exist on the presence and impact of BPA structural analogues within human ovarian follicles.

Purpose of the Study:

• To characterize exposure profiles of BPA and its alternatives in human follicular fluid (FF).
• To assess the association between bisphenol compounds (BPs) and ovarian reserve dysfunction in women with PCOS, DOR, and controls.

Main Methods:

• Collected FF samples from 104 women (15 PCOS, 34 DOR, 55 controls).
• Quantified BPA and 34 alternatives using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
• Analyzed associations using Spearman's correlation and ordinal logistic regression.

Main Results:

• Identified 24 bisphenol compounds (BPs) in FF; Bisphenol S (BPS) was most prevalent and abundant, exceeding BPA levels.
• Detected 11 BPA and 11 BPS alternatives in FF for the first time.
• Total bisphenol concentration (Σ35BPs) showed a decreasing gradient: PCOS > DOR > control; 14 BPs differed significantly between groups.
• BPA, BPAF, PHBB, DDS, and BPF were associated with abnormal ovarian reserve markers.

Conclusions:

• Confirms widespread presence of BPA alternatives in the ovarian environment.
• Suggests potential role of these alternatives in ovarian dysfunction.
• Highlights need for further mechanistic research and longitudinal studies.