This study evaluated the reproductive toxicity and reversibility of gossypol exposure in female Institute of Cancer Research (ICR) mice using the Targeted Risk Assessment of Environmental Chemicals (TRAEC) framework. Mice treated with gossypol (20 mg/kg/day, 30 days) showed reduced body weight (35.90 ± 3.19 g vs. 30.26 ± 0.91 g, p < 0.001), depletion of primordial follicles (46.2 ± 4.8 vs. 27.5 ± 3.6, p < 0.01), and impaired oocyte maturation, with polar body extrusion decreasing from 65.9% to 22.6% at 60 μM (p < 0.0001). In the human granulosa-like tumor cell line (KGN), apoptosis increased to 91.1% at 20 μg/mL compared with 11.46% in controls (p < 0.0001). Proteomic profiling identified 151 differentially expressed proteins, enriched in steroidogenesis, immune regulation, and mitochondrial metabolism. After one-month withdrawal, partial morphological recovery was observed, but endocrine function remained impaired. The TRAEC risk score of 4.68 classified gossypol as a moderate reproductive toxicant. These findings indicate that gossypol damages ovarian reserve and oocyte competence, with only partial reversibility, highlighting the need for caution in its clinical use.

Background: Bisphenols (BPs) are present in medical instruments, plastic containers, and personal care products (PCPs). Bisphenol A has been replaced by its alternatives, bisphenol S, F, AF, and B. Due to the awareness of their toxicity, mixed exposure to these alternatives at the regional level has been given less attention; there is a need to study this area of research. This meta-analysis examined the exposure of urinary bisphenol A and its metabolites to blood Hypothalamic–Pituitary–Thyroid axis hormones (HPT axis hormones) in pregnant women and adult males and females. We searched Embase, PubMed, Web of Science, Cochrane Library, and CINAHL until 8 January 2025, yielding 4588 articles using the PECO framework. Quality assessment was done using AHRQ: Agency for Healthcare Research and Quality for cross-sectional and NOS: Newcastle Ottawa Scale for cohort studies, with combined exposure evaluated using random and fixed-effect models. The I² test assessed heterogeneity. We included eighteen studies for the final analysis. Fixed-effect model estimates revealed that BPA is negatively associated with thyroid-stimulating hormone (TSH) in female and male adults (β = −0.02; 95% CI = −0.04 to −0.01); (β = −0.08; 95% CI = −0.14 to −0.02). In Females, BPA was positively associated with free thyroxine, FT4 (β = 0.001, 95% CI, 0.001 to 0.001). In the male group, BPA was negatively associated with FT4 (β = −0.001, 95% CI, −0.001 to −0.001). As per pregnant women, there was no association found between exposure to bisphenols and total Thyroxine (TT4), FT4, and TSH in both trimesters (β = 0.010, 95% CI = −0.030 to 0.050); (β = 0.001, 95% CI = −0.010 to 0.010); (β = −0.001, 95% CI = −0.010 to 0.001), respectively, for early pregnancy. Bisphenols can significantly influence HPT axis hormones in adult males, females, and pregnant women. Gender-based studies were observed, concluding that adult females are more affected by bisphenol exposures than adult males. The subgroup analysis based on the regions did not reveal any associations.