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. 2020 May;83(5):e13231.
doi: 10.1111/aji.13231. Epub 2020 Apr 12.

Association among placental 11β-HSD2, PPAR-γ, and NF-κB p65 in small-for-gestational-age infants: A nested case-control study

Lin Fu  1   2 , Qing-Li Bo  2 , Yu Gan  2 , Yuan-Hua Chen  2 , Hui Zhao  1 , Fang-Biao Tao  3 , De-Xiang Xu  2
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Association among placental 11β-HSD2, PPAR-γ, and NF-κB p65 in small-for-gestational-age infants: A nested case-control study

Lin Fu et al. Am J Reprod Immunol. 2020 May.

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.

Keywords: 11β-HSD2; AGA; NF-κB p65; PPAR-γ; SGA; placenta.

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