| Description |
Intrauterine growth restriction (IUGR) refers to the failure of a fetus to reach its genetic growth potential in utero. Each year in the United States, 5-12% of premature babies are born IUGR, which increases their risk for postnatal morbidities. One such postnatal morbidity is brochopulmonary dysplasia (BPD), in which males are more severely affected than females. Histologically, BPD is characterized by impaired alveolar development. One pathway contributing to alveolar formation is estrogen signaling. The predominate estrogen in the lung, estradiol, binds to estrogen receptors (ERs) in the cytosol, dimerizes, and translocates to the nucleus. In the nucleus, ERs bind to estrogen response elements on target genes and affect transcription, resulting in appropriate gene expression and lung development. Androgen signaling works in a similar way through the ligand testosterone and an androgen receptor (AR). Testosterone within the lung can be used to produce estradiol locally by the converting enzyme aromatase. Normal alveolar formation requires an appropriate estrogen to testosterone ratio. We hypothesize that IUGR alters lung sex steroids, estradiol to testosterone ratios, and ER/AR expression in a sex-specific manner in newborn rat lung. Uteroplacental insufficiency was induced in pregnant rats by uterine artery ligation on day 19 of gestation, producing IUGR pups. We examined 4 groups for this study: IUGR female, IUGR male, control female, and control male. Each group consisted of n=6 rat pups derived from different litters. ELISA was used to measure protein concentrations of serum and lung estradiol and testosterone, while Western blotting was used to determine ER?, ER?, and AR protein abundance relative to GAPDH. The serum and lung estrogen to testosterone ratios as well as ER? protein abundance is depressed in male but not female newborn IUGR rat pups when compared to sex-matched controls. ER? and AR expression are increased in IUGR males when compared to sex-matched controls. We conclude that IUGR alters lung sex steroids, estradiol to testosterone ratios, and ER/AR expression in a sex-specific manner in newborn rat lung. We speculate that depressed estrogen signaling in male IUGR lung may contribute to worse outcomes. |
