Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

Abstract

Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females.

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

“…Similarly, one study found that low dose BPA exposure did not affect the LH surge in adult sheep (95). Overall, the majority of the current studies suggest that BPA exposure affects the function of the anterior pituitary.…”

“…Specifically, researchers reported findings such as BPA-induced multinucleated and hemorrhagic tissue (84), multi-oocyte follicles (90), altered follicle type distribution or numbers (41, 83, 89–95), reduced ovarian weight (41, 62), and ovarian cysts (49) compared to controls. Molecular analysis revealed that high dose BPA exposure decreased the expression of Figla and oocyte-specific histone H1 variant ( H1f00 ), and increased the levels of anti-Müllerian hormone ( Amh ) genes (92).…”

Neonatal exposure to xenoestrogens impairs the ovarian response to gonadotropin treatment in lambs

“…Most studies on the effects of environmental pollutants on ovarian development and function have relied on in vitro systems or rodent models (Rodríguez et al 2010, Peretz et al 2011 and thus need to be validated in other animal models (Veiga-Lopez et al 2014). To conduct this experiment, we used sheep, a precocial species in which the reproductive developmental trajectory follows a timeline similar to that of humans (Padmanabhan et al 2007.…”

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

“…Sheep models, in particular, have been extensively used to assess pregnancy outcomes and developmental origin of diseases stemming from inappropriate exposure to native steroids and environmental steroid mimics (Padmanabhan, Sarma, Savabieasfahani, Steckler, & Veiga-Lopez, 2010). Specifically, prenatal exposure to 5 mg/kg/day BPA from gestation day GD30 to GD90 (term: 147 days), resulting in maternal BPA concentrations twofold higher than the highest values observed in pregnant US women (Padmanabhan et al, 2008;Savabieasfahani, Kannan, Astapova, Evans, & Padmanabhan, 2006), deliver low birth weight female offspring exhibiting reproductive cycle and metabolic dysfunction, including insulin resistance, adipocyte hypertrophy, and elevated proinflammatory markers in adipose tissue (Abi Salloum, Steckler, Herkimer, Lee, & Padmanabhan, 2013;Savabieasfahani et al, 2006;Veiga-Lopez, Beckett, Abi Salloum, Ye, & Padmanabhan, 2014).…”