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Am J Physiol Regul Integr Comp Physiol (July 6, 2006). doi:10.1152/ajpregu.00077.2006
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Submitted on January 27, 2006
Accepted on June 29, 2006

Long Term Hypoxia Increases Leptin Receptors and Plasma Leptin Concentrations in the Late Gestation Ovine Fetus

Charles A. Ducsay1, Kim Hyatt2, Malgorzata Mlynarczyk1, Kanchan M. Kaushal1, and Dean A. Myers2*

1 Center for Perinatal Biology, Dept. of Physiology and Pediatrics, Loma Linda University, Loma Linda, California, United States
2 Dept. of Obstetrics and Gynecology, University of Oklahoma Helath Sciences Center, Oklahoma City, Oklahoma, United States

* To whom correspondence should be addressed. E-mail: dean-myers{at}ouhsc.edu.

This study was designed to test the hypothesis that long term hypoxia (LTH) increases fetal plasma leptin and fetal adipose or placental leptin expression and alters hypothalamic and adrenocortical leptin receptor (OB-R) expression. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 to ~130 of gestation. Reduced PO2 was maintained in the laboratory by nitrogen infusion through a maternal tracheal catheter. On day 132 normoxic control and LTH fetuses underwent surgical implantation of vascular catheters (n=6/group). Five days post-surgery, maternal and fetal arterial blood samples were collected for leptin, insulin and glucose analysis. Placenta, fetal periadrenal fat, hypothalami and adrenal glands were collected from additional control (n=7) and LTH (n=8) fetuses for analysis of leptin mRNA by quantitative, real time, PCR (qRT-PCR). There was a significant (p<0.03) elevation in fetal plasma leptin in the LTH fetuses (3.5 +/- 0.7 ng/ml) vs. control (1.1 +/- 0.1 ng/ml). There were no differences in glucose or insulin concentrations between the groups. Periadrenal adipose leptin mRNA was significantly higher in the LTH group compared to control, as was placental leptin expression. Leptin mRNA in adipose was approximately 70 times higher vs. placenta. LTH significantly reduced expression of OB-Ra in the hypothalamus while resulting in a significant increase in adrenal OB-Rb expression. Our data suggest that leptin is a hypoxia-inducible gene in the ovine fetus and OB-R expression is altered by LTH. These changes may be responsible in part, for our previously observed alterations in fetal HPA function following LTH.




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