Uterine Microbiota and Bisphenols: Novel Influencers in Reproductive Health

Abstract

Infertility affects 8-12% of couples worldwide, and 30-75% of preclinical pregnancy losses are due to a failure during the implantation process. Exposure to endocrine disruptors, like bisphenols, among others, has been associated with the increase in infertility observed in the past decades. An increase in infertility has correlated with exposure to endocrine disruptors like bisphenols. The uterus harbors its own microbiota, and changes in this microbiota have been linked to several gynecological conditions, including reproductive failure. There are no studies on the effects of bisphenols on the uterine-microbiota composition, but some inferences can be gleaned by looking at the gut. Bisphenols can alter the gut microbiota, and the molecular mechanism by which gut microbiota regulates intestinal permeability involves Toll-like receptors (TLRs) and tight junction (TJ) proteins. TJs participate in embryo implantation in the uterus, but bisphenol exposure disrupts the expression and localization of TJ proteins. The aim of this review is to summarize the current knowledge on the microbiota of the female reproductive tract (FRT), its association with different reproductive diseases-particularly reproductive failure-the effects of bisphenols on microbiota composition and reproductive health, and the molecular mechanisms regulating uterine-microbiota interactions crucial for embryo implantation. This review also highlights existing knowledge gaps and outlines research needs for future risk assessments regarding the effects of bisphenols on reproduction.

Keywords: Toll-like receptors; bisphenols; fertility; microbiota; tight junctions; uterus.

Figure 1

Chemical structure of bisphenols: BPA, bisphenol A; BPAF, bisphenol AF; BPB, bisphenol B; BPF, bisphenol F; BPP, bisphenol P; BPS, bisphenol S; and TBBPA, tetrabromobisphenol A.