Neonatal exposure to xenoestrogens impaired the ovarian response to a gonadotrophin treatment in lamb

OSCAR E. RIVERA, JORGELINA VARAYOUD, HORACIO A. RODRÍGUEZ, CLARISA G. SANTAMARÍA, VERÓNICA L. BOSQUIAZZO, MARIO OSTI, NORBERTO M. BELMONTE, MÓNICA MUÑOZ-DE-TORO AND ENRIQUE H. LUQUE

REPRODUCTION

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2015

1470-1626

Bisphenol A (BPA) and Diethystilbestrol (DES) are xenoestrogens which have been associated with altered effects on reproduction. We hypothesized that neonatal xenoestrogen exposure affects the ovarian functionality in lambs. We evaluate the ovarian response to exogenous ovine Follicle Stimulating Hormone (oFSH) administered between postnatal day 30 (PND30) to PND32 in female lambs previously exposed to low doses of DES or BPA (BPA50: 50ug/kg.day, BPA0.5: 0.5 ug/kg.day) from PND1 to PND14. We determine: a) follicular growth, b) circulating levels of E2, c) steroid receptors (ERα, ERβ, AR) and atresia, d) mRNA expression levels of ovarian bone morphogenetic proteins (BMPs) system (BMP-6, BMP-15, BMP receptor type 1B, GDF-9) and FSH receptor (FSH-R). 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. The increase of E2 serum levels in response to oFSH treatment was not detected in xenoestrogens-treated lambs. In addition, the AR-induction by oFSH was disrupted in granulosa and theca cells of lambs exposed to DES or BPA. An increase of GDF-9 mRNA expression levels was observed in oFSH-primed lambs previously treated with DES or BPA50. In contrast, in BPA0.5-postnatally exposed lambs we detected a decrease of BMP-R-1B. The modifications of AR, GDF-9 and BMP-R-1B may be associated with the altered ovarian function due to neonatal xenoestrogen exposure in response to an exogenous gonadotrophic stimulus. These alterations may be the pathophysiologic basis of subfertility syndrome in adulthood