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

Abstract

Bisphenol A (BPA) and diethylstilbestrol (DES) are xenoestrogens, which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. Thus, we evaluated the ovarian response to exogenous ovine FSH (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 mg/kg per day, BPA0.5: 0.5 mg/kg per day) from PND1 to PND14. We determined: i) follicular growth, ii) circulating levels of 17b-estradiol (E 2 ), iii) steroid receptors (estrogen receptor alpha, estrogen receptor beta, and androgen receptor (AR)) and atresia, and iv) mRNA expression levels of the ovarian bone morphogenetic protein (BMPs) system (BMP6, BMP15, BMPR1B, and GDF9) and FSH receptor (FSHR). Lambs neonatally exposed to DES or BPA showed an impaired ovarian response to oFSH with a lower number of follicles R2 mm in diameter together with a lower number of atretic follicles and no increase in E 2 serum levels in response to oFSH treatment. In addition, AR induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase in GDF9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, a decrease in BMPR1B was observed in BPA0.5-postnatally exposed lambs. The modifications in AR, GDF9, and BMPR1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotropin stimulus. These alterations may be the pathophysiological basis of subfertility syndrome in adulthood.Reproduction (2015) 149 645-655

Androgen receptor and miRNA-126* axis controls follicle-stimulating hormone receptor expression in porcine ovarian granulosa cells

“…Similarly, Chen et al (2015) recently demonstrated that AR-dependent DHT inhibits FSHRdependent FSH-induced GC proliferation in rats, consistent with previous studies (Pradeep et al 2002, Kayampilly & Menon 2012. However, FSH also reduces AR expression in GCs of rats (Lu et al 2009) and sheep (Rivera et al 2015). Conversely, AR and FSHR mRNA levels are positively correlated in GCs, and low and medium doses of AR-dependent testosterone increase FSHR expression in primates (Weil et al 1999, CatteauJonard et al 2008.…”

Polymorphisms of the Ovine BMPR-IB, BMP-15 and FSHR and Their Associations with Litter Size in Two Chinese Indigenous Sheep Breeds

“…Numerous reports have shown that the FSHR gene plays a key role in animal reproduction [25,26,27]. Chu et al found two mutation (g.681T>C and g.629C>T) in the 5' flanking region of the FSHR gene in Hu sheep and three novel mutations (g.200G>A, g.197G>A and g.98T>C) in Small Tail Han Sheep [12].…”

Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle

“…The impact of such modifications on the overall estrous cycle was not determined in this study. Several other studies in sheep indicate that BPA developmental exposure (either in utero or neonatally) can alter the follicle dynamic (Rivera et al, 2011;Veiga-Lopez et al, 2014) or the ovarian response to FSH (follicular growth, FSH-induced estradiol secretion) in prepubertal animals (Rivera et al, 2015).…”