Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

Horvatiček, Marina; Perić, Maja; Bečeheli, Ivona; Klasić, Marija; Žutić, Maja; Kesić, Maja; Desoye, Gernot; Nakić Radoš, Sandra; Ivanišević, Marina; Hranilović, Dubravka; Štefulj, Jasminka (2022) Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta. Biomedicines, 10 (2). ISSN 2227-9059

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Abstract

The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.

Item Type:	Article
Uncontrolled Keywords:	development ; epigenetics ; gestational diabetes mellitus ; obesity ; pregnancy ; polymorphism ; 5-HT ; 5-HT2A
Subjects:	NATURAL SCIENCES > Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Utjecaj majčinog metaboličkog stanja na serotoninski sustav posteljice i neonatusa: od metilacije DNA do funkcije proteina Štefulj, Jasminka IP-2018-01-6547 HRZZ
Depositing User:	Maja Kesić
Date Deposited:	03 Apr 2023 12:04
URI:	http://fulir.irb.hr/id/eprint/7793
DOI:	10.3390/biomedicines10020467

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