Use of a Mouse Model of Experimentally Induced Endometriosis to Evaluate and Compare the Effects of Bisphenol A and Bisphenol AF Exposure

Abstract

Background: Endometriosis is a gynecological disease affecting 1 in 10 women of reproductive age. Endometriosis incidence has risen; however, whether this rise is due to disease awareness or environmental contamination is not known. Objective: The objective of this study was to determine if bisphenol A (BPA) or bisphenol AF (BPAF) potentiate the development of endometriosis and if hormonal status alters how toxicant exposure affects disease. Methods: A mouse model of endometriosis, where minced uterine tissue is injected into the peritoneal cavity of a host mouse, was used to examine the effects of BPA and BPAF on endometriosis lesion development in ovariectomized and hormonally intact mice. BPA and BPAF were delivered through diet to include no-observed-adverse-effect-level (NOAEL) and the low-observed-adverse-effect-level (LOAEL) exposure levels. After six weeks (at necropsy), lesions, ovaries, and blood were collected to examine characteristics, gene expression, and hormonal regulation. Results: BPA and BPAF treatments affected endometriosis in a manner specific to dose and hormonal status of the host mouse. Estrogen and endometriosis-mediated differences in lesion target gene expression also depended on hormonal status. In intact mice, ovarian steroidogenic pathways were disrupted, progesterone levels were lowered, and atretic oocyte numbers were higher with toxicant exposure. BPAF, more so than BPA, resulted in more endometriosis lesion growth, but both toxicants disrupted normal ovarian signaling. Conclusion: These findings further our understanding of the effects and hormonal impacts of BPA and BPAF on endometriosis perturbation in ovariectomized and hormonally intact mice. BPAF appeared to be similar if not more estrogenic than BPA and may be affecting an environmental contribution of the increased incidence of endometriosis. https://doi.org/10.1289/EHP3802

The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

“…Minced uterine tissue was injected into the peritoneal cavity of host mice. In this study, BPA treatment disrupted ovarian steroidogenic pathways resulting in lower progesterone levels and higher atretic oocyte numbers [60]. BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm.…”

“…BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm. Both compounds mimicked estrogen, with BPAF having a stronger effect than estrogen [60]. Taken together, these data suggest that BPA and related compounds can affect mechanisms important in the pathophysiology of endometriosis.…”

“…In an animal study [60], BPA and bisphenol AF (BPAF) affected endometriosis lesion development in ovariectomized and hormonally intact mice specific to dose and hormonal status of the host mouse. Minced uterine tissue was injected into the peritoneal cavity of host mice.…”

Association of Urinary Levels of Bisphenols A, F, and S with Endometriosis Risk: Preliminary Results of the EndEA Study

“…Specifically, BPA exposure has been associated with polycystic ovary syndrome [30], ovarian insufficiency [31], and infertility [32]. In regard to endometriosis, an in vivo study reported changes in endometrial lesions after exposure to BPA or its analogues [33], although a recent meta-analysis revealed only limited and contradictory epidemiological evidence on the association between BPA exposure and endometriosis risk [34]. By contrast, there has been no published research on the association between exposure to BPS or BPF and endometriosis.…”

DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis

“…Among those, we choose to focus our study on emerging bisphenols: Bisphenol A Diglycidyl Ether (BADGE) and Bisphenol AF (BPAF) because very little data exists on their effects on mammalian germ cells. However, recent studies have shown that, as BPA, BPAF induces the release of ROS in adult oocytes, delaying in vitro maturation (Ding et al, 2017;Jones et al, 2018).…”