Lin Fu1,2, Qing-Li Bo2, Yu Gan2, Yuan-Hua Chen2, Hui Zhao1, Fang-Biao Tao3, De-Xiang Xu2. 1. Second Affiliated Hospital, Anhui Medical University, Hefei, China. 2. Department of Toxicology, Anhui Medical University, Hefei, China. 3. Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, China.
Abstract
PROBLEM: 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) catalyzes active glucocorticoids into their inactive products, preventing the passage of glucocorticoids into the fetus from maternal circulation. Peroxisome proliferator-activated receptor (PPAR)γ is a member of the nuclear receptor superfamily that regulates the expression of placental 11β-HSD2. Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates inflammatory signaling. This study aimed to investigate the association among 11β-HSD2, PPAR-γ, and NF-κB 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 11β-HSD2 levels were measured using Western blotting. Placental PPAR-γ and NF-κB p65 were detected by immunohistochemistry. Placental inflammatory cytokines were evaluated by real-time RT-PCR. RESULTS: 11β-HSD2 levels were lower in SGA placentas than those in AGA placentas. Placental PPAR-γ-positive nuclei were less in SGA than those in AGA. By contrast, placental NF-κB p65-positive nuclei were more in SGA than those in AGA. The levels of CRP, TNF-α, IL-8, and IL-1β, several inflammatory cytokines, were higher in SGA placentas. Correlation analysis showed that neonatal weight was positively associated with PPAR-γ and 11β-HSD2 in SGA placentas. By contrast, neonatal weight was inversely correlated with NF-κB p65 in SGA placentas. 11β-HSD2 was positively correlated with PPAR-γ in SGA placentas. CONCLUSIONS: Inflammation-associated downregulation of placental PPAR-γ and 11β-HSD2 may be involved in SGA.
PROBLEM: 11β-Hydroxysteroid dehydrogenase 2 (11β-HSD2) catalyzes active glucocorticoids into their inactive products, preventing the passage of glucocorticoids into the fetus from maternal circulation. Peroxisome proliferator-activated receptor (PPAR)γ is a member of the nuclear receptor superfamily that regulates the expression of placental 11β-HSD2. Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates inflammatory signaling. This study aimed to investigate the association among 11β-HSD2, PPAR-γ, and NF-κB 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 11β-HSD2 levels were measured using Western blotting. Placental PPAR-γ and NF-κB p65 were detected by immunohistochemistry. Placental inflammatory cytokines were evaluated by real-time RT-PCR. RESULTS: 11β-HSD2 levels were lower in SGA placentas than those in AGA placentas. Placental PPAR-γ-positive nuclei were less in SGA than those in AGA. By contrast, placental NF-κB p65-positive nuclei were more in SGA than those in AGA. The levels of CRP, TNF-α, IL-8, and IL-1β, several inflammatory cytokines, were higher in SGA placentas. Correlation analysis showed that neonatal weight was positively associated with PPAR-γ and 11β-HSD2 in SGA placentas. By contrast, neonatal weight was inversely correlated with NF-κB p65 in SGA placentas. 11β-HSD2 was positively correlated with PPAR-γ in SGA placentas. CONCLUSIONS: Inflammation-associated downregulation of placental PPAR-γ and 11β-HSD2 may be involved in SGA.