Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol 2007 May;292(5):R1943-55
Date
02/03/2007Pubmed ID
17272666DOI
10.1152/ajpregu.00558.2006Scopus ID
2-s2.0-34248184460 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes toward renal insufficiency early in life and increased risk of adult-onset hypertension. In this study, we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI downregulates the key enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11beta-HSD2, and GR mRNA and protein levels, but upregulated expression of MR at birth. At day 21 of life, 11beta-HSD2, GR, and also MR mRNA and protein levels were downregulated. UPI did not affect blood pressures (BP) at day 21 of life but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult-onset hypertension.
Author List
Baserga M, Hale MA, Wang ZM, Yu X, Callaway CW, McKnight RA, Lane RHMESH terms used to index this publication - Major topics in bold
11-beta-Hydroxysteroid Dehydrogenase Type 2Aging
Animals
Cyclooxygenase 2
Down-Regulation
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Hypertension
Kidney
Placental Circulation
Placental Insufficiency
Pregnancy
RNA, Messenger
Rats
Receptors, Glucocorticoid
Receptors, Mineralocorticoid
Sex Characteristics
