Association among Placental 11β‐hsd2, PPAR‐γ, and NF‐κB P65 in Small‐for‐gestational‐age Infants: A Nested Case‐control Study

Problem: 11 beta-Hydroxysteroid dehydrogenase 2 (11 beta-HSD2) catalyzes active glucocorticoids into their inactive products, preventing the passage of glucocorticoids into the fetus from maternal circulation. Peroxisome proliferator-activated receptor (PPAR)gamma is a member of the nuclear receptor superfamily that regulates the expression of placental 11 beta-HSD2. Nuclear factor-kappa B (NF-kappa B) is a transcription factor that regulates inflammatory signaling. This study aimed to investigate the association among 11 beta-HSD2, PPAR-gamma, and NF-kappa B p65 in small-for-gestational-age (SGA) infants. Method of study: Forty-six SGA and 46 appropriate-for-gestational-age (AGA) infants were enrolled in this study. Both newborns and placentas were weighed. Placental 11 beta-HSD2 levels were measured using Western blotting. Placental PPAR-gamma and NF-kappa B p65 were detected by immunohistochemistry. Placental inflammatory cytokines were evaluated by real-time RT-PCR. Results: 11 beta-HSD2 levels were lower in SGA placentas than those in AGA placentas. Placental PPAR-gamma-positive nuclei were less in SGA than those in AGA. By contrast, placental NF-kappa B p65-positive nuclei were more in SGA than those in AGA. The levels of CRP, TNF-alpha, IL-8, and IL-1 beta, several inflammatory cytokines, were higher in SGA placentas. Correlation analysis showed that neonatal weight was positively associated with PPAR-gamma and 11 beta-HSD2 in SGA placentas. By contrast, neonatal weight was inversely correlated with NF-kappa B p65 in SGA placentas. 11 beta-HSD2 was positively correlated with PPAR-gamma in SGA placentas. Conclusions: Inflammation-associated downregulation of placental PPAR-gamma and 11 beta-HSD2 may be involved in SGA.