INDUCTION OF APOPTOSIS BY A GONADOTROPIN-RELEASING-HORMONE AGONIST DURING EARLY-PREGNANCY IN THE RAT

We have demonstrated that continuous administration of a GnRH-agonist (GnRH-Ag) in the rat during early pregnancy suppressed plasma progeste rone levels within 8 h after the commencement of treatment. The purpos e of the present study is to evaluate the hypothesis that in vivo GnRH -Ag treatment induces apoptotic cell death during early pregnancy. Rat s were treated individually on day 8 of pregnancy with 5 mu g/day of G nRH-Ag via an osmotic minipump. Sham-controlled rats received no treat ment. Rats were killed at 4, 8 or 24 h after the treatment. At autopsy , blood samples were obtained and ovaries were removed. The corpora lu tea (CL) from one ovary were removed for DNA laddering and RNA studies . As early as 8 h after the commencement of treatment, GnRH-Ag suppres sed serum progesterone levels as expected, and increased the degree of DNA degradation in the CL that was time-dependent. At 24 h after the treatment, GnRH-Ag increased the Bax, a cell death gene, expression in the CL. Collectively, these data suggest that GnRH-Ag treatment induc es apoptosis during early pregnancy in the rat.