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

RIVERA OE; VARAYOUD J; RODRÍGUEZ HORACIO ADOLFO; SANTAMARÍA, CG; BOSQUIAZZO VL; BELMONTE N; MUÑOZ DE TORO MM; LUQUE EH

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2015 vol. 149 p. 645 - 655

1470-1626

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 Follicle Stimulating Hormone (oFSH) administered from postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50 Pg/kg.day, BPA0.5: 0.5  Pg/kg.day) from PND1 to PND14. We determined: a) follicular growth, b) circulating levels of E2, c) steroid  receptors (ERA, ERB, AR) and atresia, d)  mRNA expression levels of the ovarian bonemorphogenetic protein (BMPs) system (BMP6,  BMP15,  BMP receptor type 1B,  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  >? 2 mm together with a lower  number of atretic follicles and no increase in E2  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