Differential effects of the endocrine-disrupting compounds Bisphenol-A and Octylphenol on gonadotropin secretion, in prepubertal ewe lambs☆

Abstract This study examined the effects of long-term exposure to the endocrine-disrupting compounds (EDCs) Bisphenol-A (BPA) and Octylphenol (OP) on gonadotrophin secretion in pre-pubertal female sheep. Four-week-old, female lambs were randomly allocated to four groups ( n =6), and twice each week treated with i.m. injections of either corn oil (vehicle controls), diethylstilbestrol (DES; 0.175 mg/kg), BPA (3.5 mg/kg) or OP (3.5 mg/kg). After 5 weeks of treatment, animals were ovariectomized (ovx) and ovary weights recorded. Two weeks later, blood samples were collected from lambs every 15 min for 6 h, for LH pulse analysis. Animals were then euthanased and adrenal and kidney weight recorded. An age-related increase in tonic LH secretion was noted in Control, BPA- and OP-treated lambs, but was absent in DES-treated lambs. Following ovx, LH secretion increased in all except DES-treated lambs; FSH concentrations increased in all groups. BPA and DES significantly suppressed LH pulse frequency (C: 6.7±0.3 pulses/6 h, DES: 1.5±0.8 pulses/6 h, BPA: 2.3±0.8 pulses/6 h) and amplitude (C: 7.1±1.0 ng/ml, DES: 1.9±0.6 ng/ml, BPA: 1.6±0.4 ng/ml). OP had no effect on LH secretion (Frequency: 5.8±0.5 pulses/6 h, amplitude: 8.0±2.0 ng/ml). Ovary weight was similar among all groups. Results show that chronic in vivo exposure of prepubertal female lambs to BPA, at levels lower than those reported previously, can have significant effects on LH secretion that are comparable to those seen following exposure to the known xenoestrogen, DES. Exposure to an equal dose of the EDC OP, over the equivalent period of time was without effect on gonadotropin secretion in the prepubertal ewe lamb. These results indicate that exposure of prepubertal female lambs to the EDC BPA can induce significant effects on gonadotropin secretion, the potential long-term effects of exposure and the effects of these changes on reproductive performance and efficacy, therefore, merit further study.