Although maternal nurturing behavior is extremely important for the preservation of a species, our knowledge of the biological underpinnings of these behaviors is insufficient. Here we show that the degree of a mother's nurturing behavior is regulated by factors present during her own fetal development. We found that Cin85-deficient () mother mice had reduced pituitary hormone prolactin (PRL) secretion as a result of excessive dopamine signaling in the brain. Their offspring matured normally and produced their own pups; however, nurturing behaviors such as pup retrieval and nursing were strongly inhibited. Surprisingly, when WT embryos were transplanted into the fallopian tubes of mice, they also exhibited inhibited nurturing behavior as adults. Conversely, when embryos were transplanted into the fallopian tubes of WT mice, the resultant pups exhibited normal nurturing behaviors as adults. When PRL was administered to mice during late pregnancy, a higher proportion of the resultant pups exhibited nurturing behaviors as adults. This correlates with our findings that neural circuitry associated with nurturing behaviors was less active in pups born to mothers, but PRL administration to mothers restored neural activity to normal levels. These results suggest that the prenatal period is extremely important in determining the expression of nurturing behaviors in the subsequent generation, and that maternal PRL is one of the critical factors for expression. In conclusion, perinatally secreted maternal PRL affects the expression of nurturing behaviors not only in a mother, but also in her pups when they have reached adulthood.

Elucidating the mechanisms underlying nurturing and neglect behaviors is meaningful but challenging. Recently, we found that CIN85-deficient mice had reduced pituitary hormone prolactin secretion during late pregnancy, and their pups later showed an inhibited nurturing behavior. To examine whether this phenomenon could be reproduced in normal mice and not just CIN85-deficient mice, we investigated the nurturing behavior of offspring born to mothers whose blood prolactin levels had been reduced by bromocriptine administration during late pregnancy. First, to determine when bromocriptine treatment should be started, we investigated the detailed changes in blood prolactin levels in late pregnancy in mice, resulting in the identification of the prepartum prolactin surge. Furthermore, prolactin receptors in the fetal hypothalamus were expressed to the same extent as in the adult hypothalamus. Treatment with bromocriptine decreased the plasma concentrations of prolactin to the basal range throughout late pregnancy. However, against expectations, the proportion of the resultant pups exhibiting nurturing behaviors as adults was as high as that in the mice without bromocriptine treatment. In conclusion, the elimination of prolactin secretion during late pregnancy alone does not induce neglect-like behavior in offspring, suggesting that CIN85-deficient mice appear to involve another factor due to CIN85 deficiency besides prolactin deficiency.