Submitted on January 3, 2008
Accepted on February 17, 2008
Long Term Hypoxia Modulates Expression of Key Genes Regulating Adipose Function in the Late Gestation Ovine Fetus
Dean A. Myers1*, Krista Hanson1, Malgorzata Mlynarczyk2, Kanchan M. Kaushal3, and Charles A. Ducsay4
1 Dept of Obstetrics and Gynecology,, University of Oklahoma HSC, Oklahoma City, Oklahoma, United States
2 Center for Perinatal Biology, Loma Linda University, Loma Linda , California, United States
3 United States; Center for Perinatal Biology, Loma Linda University, United States
4 Center for Perinatal Biology, Loma Linda University, United States
* To whom correspondence should be addressed. E-mail: dean-myers{at}ouhsc.edu.
A major function of abdominal adipose in the newborn is non-shivering thermogenesis. Uncoupling protein (UCP) 1 and UCP2 play major roles in thermogenesis. The present study tested the hypothesis that LTH modulates expression of UCP1 and 2, and key genes regulating expression of these genes in the late gestation ovine fetus. Ewes were maintained at high altitude (3,820 m) from 30-138 days gestation (dG); perirenal adipose was collected from LTH and age-matched, normoxic control fetuses at 139-141 dG. Quantitative real-time PCR was used to analyze mRNA for UCP1, UCP2, 11 
hydroxysteroid dehydrogenase type 1 (HSD11B1) and 2 (HSD11B2), glucocorticoid receptor (GR), 3 adrenergic receptor (3AR), deiodinase type 1 (DIO1) and DIO2, peroxisome proliferator activated receptor (PPAR) 
and 
and PPAR co-activator 1 (PGC1). Concentrations of mRNA for UCP1, HSD11B1, PPAR, PGC1, DIO1 and DIO2 were significantly higher in perirenal adipose of LTH compared to control fetuses, while mRNA for HSD11B2, GR, or PPAR in perirenal adipose did not differ between control and LTH fetuses. The increased expression of UCP1 is likely an adaptive response to LTH assuring adequate thermogenesis in the event of birth under oxygen-limiting conditions. Since both glucocorticoids and thyroid hormone regulate UCP1 expression, the increase in HSD11B1, DIO1 and DIO2 implicate increased adipose capacity for local synthesis of these hormones. PPAR and its co-activator may provide an underlying mechanism via which LTH alters development of the fetal adipocyte. These findings have important implications regarding fetal/neonatal adipose tissue function in response to LTH.
