From
early pregnancy levels of prolactin increase dramatically, which leads to an
increase in maternal gestational neurogenesis in the subventricular zone of the
lateral ventricle (SVZ). As SVZ neurogenesis generates new olfactory neurons,
which may contribute to perception of offspring, we hypothesized that the
prolactin-induced increase in neurogenesis might be important for normal
maternal behaviors. When prolactin secretion was suppressed early in pregnancy
in mice, to prevent the normal increase in maternal neurogenesis, maternal
anxiety was significantly increased postpartum, and maternal behavior markedly
impaired. Injections of the mitotic inhibitor, methylazoxymethanol1,
to specifically suppress maternal neurogenesis without affecting prolactin
secretion, also caused postpartum anxiety and impaired maternal behavior. These
data demonstrated that the prolactin-induced increase in maternal SVZ
neurogenesis during pregnancy is required for normal expression of postpartum
maternal behaviors. In this model of postpartum anxiety we observed that
daughters of anxious mothers had delayed onset of puberty. Correct levels of
reproductive neurons are essential for normal reproductive physiology. Hence,
we hypothesized that decreased levels of prolactin in the mother during early
pregnancy alters neuronal development in offspring. Female fetuses of low
prolactin (anxious) mothers had an increase in DNA methylation on day 9, but
not day 7 of gestation, compared to control fetuses, demonstrating a change in
the pattern of gene expression. Levels of neuronal apoptosis were increased on
postnatal day 4 in both first and third generation daughters of anxious
mothers, and this was associated with reduced kisspeptin expression in the
hypothalamus of immature and adult female offspring. These results indicate
that low levels of prolactin during early pregnancy not only significantly
affect maternal behaviors, but also have a sustained and persistent effect on
the reproductive physiology of female offspring.
- 1. Acknowledgement: This project was performed, in part using a compound provided by the National Cancer Institute's Chemical Carcinogen Reference Standards Repository operated under contract by Midwest Research Institute, NO. N02-CB-66600.
- This work was supported by a: New Zealand Lottery Commission Health Research Grant, Anderson and Telford Trust Grant, University of Otago Health Sciences Postdoctoral Fellowship, Marsden Fast Start Grant.