hrvatski jezikClear Cookie - decide language by browser settings

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; Hranilovic, 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

PDF - Published Version - article
Available under License Creative Commons Attribution.

Download (2MB) | Preview


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
INTERDISCIPLINARY AREAS OF KNOWLEDGE > Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area
Divisions: Division of Molecular Biology
Project titleProject leaderProject codeProject type
Utjecaj majčinog metaboličkog stanja na serotoninski sustav posteljice i neonatusa: od metilacije DNA do funkcije proteinaŠtefulj, JasminkaIP-2018-01-6547HRZZ
Depositing User: Sofija Konjević
Date Deposited: 11 Mar 2022 10:46
DOI: 10.3390/biomedicines10020467

Actions (login required)

View Item View Item


Downloads per month over past year

Increase Font
Decrease Font
Dyslexic Font