Expression level of long noncoding RNA H19 of normotensive placentas in late pregnancy relates to the fetal growth restriction

• Published in: The journal of obstetrics and gynaecology research 2020-07, Vol.46 (7), p.1025-1034
• Main Authors: Tsunoda, Youhei, Kudo, Mitsuhiro, Wada, Ryuichi, Ishino, Kousuke, Kure, Shoko, Sakatani, Takashi, Takeshita, Toshiyuki, Naito, Zenya
• Format: Article
• Language: English
• Subjects: Decorin; Endothelial cells; fetal growth restriction; Fetuses; Fibrosis; Gestational age; H19; H19 gene; Health risk assessment; Hybridization; in situ hybridization; Infants; Insulin-like growth factor II; Localization; long noncoding RNA; Morbidity; Neonates; Paraffin; Placenta; placental pathology; Polymerase chain reaction; Pregnancy; Reverse transcription; Ribonucleic acid; RNA; Small-for-gestational age; Stroma
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/jog.14260

Aim Infants with fetal growth restriction (FGR) are at an increased risk of perinatal morbidity and mortality. The long noncoding RNA H19 gene is expressed abundantly in placental villi and recent studies suggest that it regulates FGR. However, the role of H19 in the FGR placenta remains unclear. This study aimed to clarify the relationship between H19 expression and FGR using normotensive placentas after 34 weeks of gestation. Methods Formalin‐fixed paraffin‐embedded tissues from human placentas collected from pregnancies resulting in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns were used. The histopathological features of placenta tissues, such as villous stromal fibrosis, the numbers of terminal villi, villous vessels and cytotrophoblasts were analyzed using hematoxylin and eosin, Masson's trichrome staining and immunostaining. The localization and expression of H19 in the placentas were demonstrated by in situ hybridization and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR), respectively. Moreover, the expression levels of H19‐regulated molecules such as IGF2 and decorin (DCN) were measured by RT‐qPCR. Results Histopathological features of the placental villous were not different between placentas associated with SGA and AGA. H19 localized to the villous stroma, endothelial cells and cytotrophoblasts. Moreover, the expression level of H19 in SGA placentas was significantly lower than that in AGA placentas. The expression levels of IGF2 and DCN in SGA placentas tended to be lower than those in AGA placentas similarly to H19. Conclusion This study highlights the potential importance of regulatory events mediated by H19 in SGA placentas without histopathological abnormalities in late pregnancy.