ANTIPROGESTERONE ANTIBODY ADMINISTRATION AND THE IMPAIRMENT OF POSTPARTUM MATERNAL-CARE IN MICE

Passive transfer of a monoclonal antibody against progesterone produce s a high incidence of maternal rejection in mice after recovery from a ntibody-induced infertility. To investigate the mechanism involved in this reduction of maternal care, we have examined whether the effect i s due to long-term exposure to antibody. Antibody was administered i.p . either on day 2 or day 17 of pregnancy. When a low dose (1.0 nmol) w as given on day 2, pregnancy proceeded normally but 44.8% pups deliver ed at term were rejected compared with 12.7% in the control group. Whe n a higher dose (4.5 nmol) of antibody was given on day 17, pregnancy continued normally to term and the rejection rate was 48.8% (control: 11.1%). When the same amount of antibody was injected after delivery ( day 1 of lactation), no detrimental effect was found on subsequent mat ernal care to the young, the rejection rate being comparable between a ntibody-treated and control groups (5.3% vs 4.6%). To determine if the presence of antibody interfered with lactation or suckling, a bolus i njection of 10 mu Ci ([)3H]H2O was given to mice treated at day 17 wit h antibody or saline. The levels of radioactivity present in both moth ers and pups and the first 5-day pup growth curves showed identical pa tterns, indicating that milk availability and the suckling process wer e not affected. Crossfostering studies revealed that antibody-treated mothers rejected 25.5% of fostered pups compared with 8.5% found in th e control females when antibody was administered on day 17 of pregnanc y and the entire Litters were crossfostered between the two soups imme diately after delivery. Detailed analyses using a retrieval test furth er demonstrated that the reduction in maternal care was most pronounce d during the first 3 days after delivery. These results demonstrate th at antibody-treated mothers show a higher frequency of pup rejection w hich is (i) not restricted to their own litter; (ii) not due to lack o f milk; and (iii) not a result of defects in the pups. They are consis tent with the hypothesis that anti-progesterone antibody interferes wi th the priming mechanism(s) necessary for the onset of maternal behavi our during the 3-day period prior to delivery, leading to impaired mat ernal care after parturition.