The biological effects of bisphenol AF in reproduction and development: What do we know so far?

Due to the established endocrine-disrupting effects of Bisphenol A (BPA), alternative bisphenols entered the market. Bisphenol AF (BPAF) is now commonly used in the industrial manufacturing of polycarbonate plastics and epoxy resins. However, BPAF's effects on reproduction and development have not been thoroughly reviewed. We investigated the relationship between BPAF exposure and reproduction and early development. We performed a literature review of studies on BPAF and reproductive physiology. Using keywords, we searched PubMed, Medline, Cochrane Library Database, Embase, and ClinicalTrials.gov for English language literature available until December 2024; we additionally identified and included studies from bibliographies. We included 125 articles, spanning in vitro and in vivo model organism and human studies. BPAF is a selective estrogen receptor modulator and an androgen receptor antagonist and is more potent than BPA. It is detected in urine, blood products, saliva, amniotic fluid, and breast milk. In vitro and in vivo studies demonstrate a spectrum of BPAF-induced endocrine and reproductive changes in both sexes. There is strong evidence of alterations in the hypothalamic-pituitary-gonadal axis and of altered steroidogenesis pathways. Multiple studies using zebrafish, Xenopus, chickens, and rodents, show BPAF's effects on embryogenesis, morphology, and sexual differentiation. Decreased serum testosterone and impaired spermatogenesis and oocyte viability have been demonstrated. The current literature shows clear disruptive effects of BPAF on reproductive health and embryonic development. Though further investigation is warranted, there is ample converging evidence to support limiting the use of BPAF and other similar bisphenols.