Anti-fertility effect of passive immunization against progesterone is influenced by genotype

The anti-fertility effect of a monoclonal progesterone antibody injected i.p. 32 h after mating is influenced by genotype since a single dose of 5.7 nmol immunoglobulin G successfully blocked the establishment of pregnancy in BALB/c but not in F1 hybrid mice (CBA male X BALB/c female). Progesterone concentrations in circulation were significantly higher at days 3 and 4 after mating in F1 females compared with those of the BALB/c stock. Moreover, the pattern of mitotic activity in the endometrium after passive immunization differed between the two genotypes. In treated BALB/c mice there was no increase in mitotic activity in stromal cells at days 3, 4 and 5 after mating (in contrast to BALB/c control females in which the number of stromal mitoses increased sharply). In F1 females there was a transient effect of antibody at day 3 (no increase in stromal mitoses but enhanced mitotic activity in the glandular epithelium compared with F1 control females), and subsequently a normal increase in mitotic divisions in stromal cells. The hypothesis is proposed that passive immunization against progesterone at 32 h after mating will only block the establishment of pregnancy in genotypes in which there is a gradual, rather than a steep rise in circulating progesterone concentrations during the preimplantation period. In F1 mice, high concentrations of circulating progesterone at days 3 and 4 of pregnancy apparently over-ride the effect of antibody and facilitate the normal development of stromal mitotic activity associated with the onset of implantation.