Editors' ChoiceNeuroscience

Teaching the Fetal Hypothalamus

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Science Translational Medicine  28 Sep 2011:
Vol. 3, Issue 102, pp. 102ec158
DOI: 10.1126/scitranslmed.3003237

We all know that mothers pass knowledge along to their daughters, and they in turn to their daughters, and so on through the generations. What we did not know is that when it comes to teaching the hypothalamus how to behave during pregnancy, the placenta is key. Now, Broad and Keverne demonstrate synchronized gene expression between the placenta and hypothalamus during a key stage of development for both organs.

During embryonic days (E) 11 to 14 in the mouse, the hypothalamus undergoes most of its maturation while at the same time the placenta is generating vasculature and hormone-producing giant cells. Broad and Keverne found that the proportion of genes with synchronized expression between the embryonic hypothalamus and the maternal placenta increases significantly from 9% of all gene changes on E11–12 to 44% on E12–13. Thus, E12–13 is a key developmental time point at which the hypothalamus and placenta become genetically “in tune” with one another. This synchronization process was interrupted by 24 hours of maternal food deprivation, resulting in inactivation of paternally-expressed gene 3 (Peg3), which plays a role in the generation of oxytocin neurons that are important for parturition and maternal care. This interrupted gene synchronization was from changes in the placenta; hypothalamic gene expression was spared, and in fact, hypothalamic Peg3 expression increased. The food deprivation–induced alterations in placental gene expression affected proteolysis and lipolysis, pathways activated in response to starvation to provide calories to the fetus. Thus, the fetal brain was shielded from maternal caloric stress, in part by the placenta.

Broad and Keverne hypothesize that the spike of synchronized gene expression between the fetal hypothalamus and the placenta help to program the developing hypothalamus for optimal function in adulthood in response to signals from the next generation’s placenta. Variations in the expression of placenta-hypothalamus coordinated genes may lead to consequences for mother (such as poor milk letdown) and baby (such as failure to suckle). Understanding the genetic tuning between the placenta and the hypothalamus may yield insights into how innate maternal responses are transmitted across generations and into the mechanism of dysfunctional reproduction-related processes.

K. D. Broad, E. B. Keverne, Placental protection of the fetal brain during short-term food deprivation. Proc. Natl. Acad. Sci. U.S.A. 108, 15237–15241 (2011). [Abstract]

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