SUPPRESSION OF FETAL GONADOTROPIN CONCENTRATIONS BY MATERNAL PASSIVE-IMMUNIZATION TO GNRH IN SHEEP

The hypothalamo-pituitary-gonadal axis matures during fetal life and m ay be susceptible to adverse effects. Model systems can be used to und erstand 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 secret ion. 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 I day and a suppression of the pulsatile secretion of fetal LH after 2 days. Fetal FSH concentrations declined gradually ove r the II 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 shor t term changes in GnRH release. The lack of a suppressive effect of th e 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 mat ernal 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 b arrier and suppressing fetal LH and FSH secretion in males, but only s uppressing LH secretion in the females. Although the lack of effect on FSH secretion in the females needs to be investigated further, the pr esent study provides evidence of a non-invasive procedure for blocking fetal gonadotrophin secretion which may be used to investigate hypoth alamo-pituitary-gonadal The hypothalamo-pituitary-gonadal axis matures during fetal life and may be susceptible to adverse effects. Model sy stems can be used to understand its physiological role. The aim of thi s study was to determine whether antibodies to GnRH, administered to t he mother, can cross the ovine fetal-placental barrier and suppress fe tal gonadotrophin secretion. Maternal passive immunization to GnRH in pregnant Greyface ewes (day 103 of gestation) resulted in GnRH antibod y titres of from 1:6000 to 1:9000 after I day and a suppression of the pulsatile secretion of fetal LH after 2 days. Fetal FSH concentration s declined gradually over the II 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 ef fect of oestradiol and, possibly, inhibin. There was no sexual dimorph ism in the effect of maternal GnRH immunoneutralization on fetal GnRH antibody titres or fetal LH secretion. These findings show that matern al passive immunization against GnRH results in GnRH antibodies crossi ng the fetal-placental barrier and suppressing fetal LH and FSH secret ion in males, but only suppressing LH secretion in the females. Althou gh the lack of effect on FSH secretion in the females needs to be inve stigated further, the present study provides evidence of a non-invasiv e procedure for blocking fetal gonadotrophin secretion which may be us ed to investigate hypothalamo-pituitary-gonadal function during early gestation in sheep.