Suppression of fetal gonadotrophin concentrations by maternal passive immunization to GnRH in sheep.

Abstract

The hypothalamo-pituitary-gonadal axis matures during fetal life and may be susceptible to adverse effects. Model systems can be used to understand its physiological role. The aim of this study was to determine whether antibodies to GnRH, administered to the mother, can cross the ovine fetal-placental barrier and suppress fetal gonadotrophin secretion. Maternal passive immunization to GnRH in pregnant Greyface ewes (day 103 of gestation) resulted in GnRH antibody titres of from 1:6000 to 1:9000 after 1 day and a suppression of the pulsatile secretion of fetal LH after 2 days. Fetal FSH concentrations declined gradually over the 11 days of the experiment and were only significantly different from control animals immunized against BSA in male fetuses. The slower decrease in fetal FSH concentrations than in LH concentrations shows that the secretion of FSH, unlike that of LH, is not dependent on short term changes in GnRH release. The lack of a suppressive effect of the maternal GnRH immunoneutralization on female fetal FSH secretion may be due to removal of the negative feedback effect of oestradiol and, possibly, inhibin. There was no sexual dimorphism in the effect of maternal GnRH immunoneutralization on fetal GnRH antibody titres or fetal LH secretion. These findings show that maternal passive immunization against GnRH results in GnRH antibodies crossing the fetal-placental barrier and suppressing fetal LH and FSH secretion in males, but only suppressing LH secretion in the females. Although the lack of effect on FSH secretion in the females needs to be investigated further, the present study provides evidence of a non-invasive procedure for blocking fetal gonadotrophin secretion which may be used to investigate hypothalamo-pituitary-gonadal function during early gestation in sheep.