Ontogenic expression of putative feeding peptides in the rat fetal brain and placenta
R Beloosesky1, D A Gayle, F Amidi
1Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA.
Insights
Fetal development influences appetite regulation. Key appetite peptides like AgRP, CART, and OB-Rb show dynamic changes in the fetal brain and placenta, suggesting in utero programming of feeding behaviors.
Area of Science:
- Neuroscience
- Developmental Biology
- Endocrinology
Background:
- The fetal programming paradigm highlights how the intrauterine environment impacts long-term health.
- Appetite regulation involves complex neural pathways that develop during gestation.
Purpose of the Study:
- To investigate the ontogenic expression of appetite-regulatory peptides in the fetal rat brain and placenta.
- To compare fetal feeding peptide expression with adult brain patterns.
Main Methods:
- Real-time RT-PCR was used to quantify mRNA levels of orexigenic (NPY, AgRP) and anorexigenic (CART, POMC) peptides and leptin receptor (OB-Rb).
- Fetal brain and placental tissues were collected at gestational days 14, 16, and 18.
- Adult rat brain regions (hypothalamus, cortex, cerebellum) were also analyzed.
Main Results:
- Agouti-related peptide (AgRP) mRNA levels significantly decreased in the fetal brain and placenta from day 14 to day 18.
- Leptin receptor (OB-Rb) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels increased during this period.
- Neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) expression remained stable.
Conclusions:
- Dynamic changes in appetite-regulating peptides during late gestation suggest critical developmental processes.
- The expression pattern in the fetal brain resembles that of the adult cerebral cortex.
- These findings support the concept of in utero programming of ingestive behavior and appetite regulation.
Abstract:
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 for mRNA 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.
