Ontogenic expression of putative feeding peptides in the rat fetal brain and placenta

The well-demonstrated "fetal programming" paradigm is based on the observation that environmental changes can reset the developmental path and thus, gene expression during intrauterine development. As appetite-regulatory neural pathways develop in utero, we sought to determine the ontogenic expression of putative orexigenic and anorexigenic feeding-regulatory peptides in the fetal rat brain and placenta during the last third of gestation. Pregnant Sprague-Dawley rats(n=12) at D14, D16 and D18 were sacrificed and fetal whole brain and placenta removed and examined form RNA levels of orexigenic (neuropeptide Y(NPY), agouti-related peptide (AgRP)) and anorexigenic (cocaine and amphetamine regulated transcript ( CART), pro-opiomelanocortin ( POMC)) peptides and leptin receptor (OB-Rb) using real-time reverse transcription polymerase chain reactions (RT-PCR). For adult comparisons, the hypothalamus, cortex and cerebellum from male rats were also examined for feeding peptides. In the fetal brain and placenta, mRNA levels of AgRP decreased 10-fold from D14 to D16 and was undetectable at D18. Appetite inhibitory factors OB-Rb and CART mRNA levels increased from D14 to D18 in the brain and placenta. NPY and POMC expression remained unchanged from D14 to D18. The pattern of expression of feeding regulatory peptides in the fetal brain most closely resembled the expression profile of the adult cerebral cortex. The continued maturation of feeding regulatory mechanisms in late gestation indicates the potential for in utero programming of ingestive behavior.