Passive transfer of a monoclonal antibody against progesterone produces a high incidence of maternal rejection in mice after recovery from antibody-induced infertility. To investigate the mechanisms involved in this reduction of maternal care, we have examined whether the effect is 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) was given on day 2, pregnancy proceeded normally but 44·8% pups delivered at term were rejected compared with 12·7% in the control group. When 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 maternal care to the young, the rejection rate being comparable between antibody-treated and control groups (5·3% vs 4·6%).
To determine if the presence of antibody interfered with lactation or suckling, a bolus injection of 10 μCi [3H]H2O was given to mice treated at day 17 with antibody or saline. The levels of radioactivity present in both mothers and pups and the first 5-day pup growth curves showed identical patterns, indicating that milk availability and the suckling process were not affected. Crossfostering studies revealed that antibody-treated mothers rejected 25·5% of fostered pups compared with 8·5% found in the control females when antibody was administered on day 17 of pregnancy and the entire litters were crossfostered between the two groups immediately after delivery. Detailed analyses using a retrieval test further demonstrated that the reduction in maternal care was most pronounced during the first 3 days after delivery.
These results demonstrate that antibody-treated mothers show a higher frequency of pup rejection which is (i) not restricted to their own litter; (ii) not due to lack of milk; and (iii) not a result of defects in the pups. They are consistent with the hypothesis that anti-progesterone antibody interferes with the priming mechanism(s) necessary for the onset of maternal behaviour during the 3-day period prior to delivery, leading to impaired maternal care after parturition.
Journal of Endocrinology (1995) 145, 363–369
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