Bisphenol A exposure inhibits germ cell nest breakdown by reducing apoptosis in cultured neonatal mouse ovaries

Abstract

Bisphenol A is a known endocrine disrupting chemical and reproductive toxicant. Previous studies indicate that in utero BPA exposure increases the percentage of germ cells in nests and decreases the percentage of primordial follicles. However, the mechanism by which BPA affects germ cell nest breakdown is unknown. Thus, we hypothesized that BPA inhibits germ cell nest breakdown by interfering with oxidative stress and apoptosis pathways. To test our hypothesis, ovaries from newborn mice were collected and cultured with vehicle (dimethyl sulfoxide, DMSO) or different doses of BPA (0.1, 1, 5, and 10 μg/mL). Ovaries then were subjected to histological evaluation of germ cell nests and primordial follicles or to measurements of factors that regulate oxidative stress and apoptosis. Our results indicate that in vitro BPA exposure significantly inhibits germ cell nest breakdown by altering the expression of key ovarian apoptotic genes, but not by interfering with the oxidative stress pathway.

Evidence for bisphenol A-induced female infertility: a review (2007–2016)

“…In mice, in vitro studies of isolated neonatal ovaries indicate that high dose BPA exposure inhibited germ cell nest breakdown and accelerated primordial follicle recruitment compared to controls (99, 100), similar to some of the observations in in vivo studies. Specifically, BPA exposure decreased levels antigen KI-67 ( Ki67 ), tumor necrosis factor receptor superfamily member 6 ( Fas ), and caspases ( Casp3 and 8 ) (99, 100).…”

“…Specifically, BPA exposure decreased levels antigen KI-67 ( Ki67 ), tumor necrosis factor receptor superfamily member 6 ( Fas ), and caspases ( Casp3 and 8 ) (99, 100). Further, BPA increased levels of Bcl2 and factors related to the phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/Akt) signaling pathway (99, 100).…”

“…Specifically, BPA exposure decreased levels antigen KI-67 ( Ki67 ), tumor necrosis factor receptor superfamily member 6 ( Fas ), and caspases ( Casp3 and 8 ) (99, 100). Further, BPA increased levels of Bcl2 and factors related to the phosphatidylinositol 3-kinase/thymoma viral proto-oncogene (PI3K/Akt) signaling pathway (99, 100). In sheep fetal ovaries, low dose BPA exposure resulted in an age-dependent increase in expression of steroidogenic genes, mammalian target of rapamycin ( mTor ), peroxisome proliferator-activated receptor ( Pparα ), and Igf1r compared to controls (101).…”

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

“…[70]). Zhou et al [71] revealed that bisphenol A exposure significantly inhibited germ cell nests breakdown by altering the expression of key ovarian apoptotic genes in cultured neonatal mouse ovaries. Interestingly, exposure of neonates to estrogenic compounds like bisphenol A significantly increases the number of multiple oocyte follicles (MOFs) in adult mice ovaries.…”

An old culprit but a new story: bisphenol A and “NextGen” bisphenols

“…Importantly, the subtle meiotic changes induced during this fetal stage of oogenesis increase the frequency of chromosomally abnormal eggs and embryos in the adult (31). Exposure at a slightly later stage of development (late gestation in the rhesus monkey and immediately after birth in the mouse) disrupts the formation of ovarian follicles, leading to the generation of multioocyte follicles and unenclosed oocytes (32, 34, 35), altering viable follicle populations in the adult. Given these experimental data, the expectation for adult women exposed in utero would be, as follows: [1] an increase in pregnancy failure and birth defects, if exposure coincides with the onset of meiosis in the fetal ovary, and [2] a decreased ovarian reserve and potential shortening of the reproductive lifespan, if exposure occurs at the time of follicle formation.…”