UTEROPLACENTAL INSUFFICIENCY AFFECTS RENAL EXPRESSION OF ESTROGEN RECEPTORS IN INTRAUTERINE GROWTH-RESTRICTED RATS.

Abstract

Background Uteroplacental insufficiency results in intrauterine growth restriction (IUGR). IUGR newborns are at an increased risk for later development of morbidities, including hypertension, at an incidence that varies between genders. Although we have previously demonstrated differences in gender-specific gene expression in the IUGR rat kidney, it is unknown whether IUGR affects kidney expression of either the androgen or estrogen receptors. Objective We hypothesized that IUGR would alter renal mRNA levels of the androgen receptor (AR), estrogen receptor 1 (ER1), and estrogen receptor 2 (ER2) in a gender-specific manner in day 0 (d0) and day 21 (d21) IUGR rat pups. Methods Bilateral uterine artery ligation was performed on day 19 pregnant Sprague-Dawley rats to render them IUGR, and pups were then harvested on day 21 (term). Levels of AR, ER1, and ER2 mRNA were quantified using real-time RT-PCR from whole kidneys on days 0 and 21. Results mRNA levels expressed as % of control ⊆ SEM. IUGR significantly increased renal ER1 mRNA levels in d21 males to 177 ⊆ 16.* In contrast, ER2 mRNA levels were significantly decreased to 57 ⊆ 6** in day 21 female kidneys. Identical changes in the ER1 and ER2 mRNA levels were seen in day 0 males and females but did not achieve statistical significance. *p Conclusions IUGR increases ER1 receptor expression in IUGR male rats while decreasing ER2 receptor expression in IUGR female rats. Interestingly, the differences in gene expression widens from day 0 to day 21 in the IUGR rat kidney. We speculate that such differences contribute to the gender-specific characteristics of the IUGR rat kidney.