Dataset Information

Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

ABSTRACT: Placental growth is most rapid during the first trimester (FT) of pregnancy, making it vulnerable to metabolic and endocrine influences. Obesity, with its inflammatory and oxidative stress, can cause cellular damage. We hypothesized that maternal obesity increases DNA damage in the FT placenta, affecting DNA damage response and trophoblast turnover. Examining placental tissue from lean and obese non-smoking women (4-12 gestational weeks), we observed higher overall DNA damage in obesity (COMET assay). Specifically, DNA double-strand breaks were found in villous cytotrophoblasts (vCTB; semi-quantitative γH2AX immunostaining), while oxidative DNA modifications (8-hydroxydeoxyguanosine; FPG-COMET assay) were absent. Increased DNA damage in obese FT placentas did not correlate with enhanced DNA damage sensing and repair. Indeed, obesity led to reduced expression of multiple DNA repair genes (mRNA array), which were further shown to be influenced by inflammation through in vitro experiments using tumor necrosis factor-α treatment on FT chorionic villous explants. Tissue changes included elevated vCTB apoptosis (TUNEL assay; caspase-cleaved cytokeratin 18), but unchanged senescence (p16) and reduced proliferation (Ki67) of vCTB, the main driver of FT placental growth. Overall, obesity is linked to heightened non-oxidative DNA damage in FT placentas, negatively affecting trophoblast growth and potentially leading to temporary reduction in early fetal growth.

SUBMITTER: Hoch D

PROVIDER: S-EPMC11347397 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

Hoch Denise D Majali-Martinez Alejandro A Bandres-Meriz Julia J Bachbauer Martina M Pöchlauer Caroline C Kaudela Theresa T Bankoglu Ezgi Eyluel EE Stopper Helga H Glasner Andreas A Hauguel-De Mouzon Sylvie S Gauster Martin M Tokic Silvija S Desoye Gernot G

Molecular human reproduction 20240801 8

Placental growth is most rapid during the first trimester (FT) of pregnancy, making it vulnerable to metabolic and endocrine influences. Obesity, with its inflammatory and oxidative stress, can cause cellular damage. We hypothesized that maternal obesity increases DNA damage in the FT placenta, affecting DNA damage response and trophoblast turnover. Examining placental tissue from lean and obese non-smoking women (4-12 gestational weeks), we observed higher overall DNA damage in obesity (COMET a ...[more]

PMID: 39092995

Similar Datasets

Project description:Oxidative stress plays a crucial role in preeclampsia (PE) pathogenesis. Evidence indicates altered microRNAs (miRNAs) expression in PE, however, the relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in PE is not fully elucidated. In the present study, we investigate the impact of increased oxidative stress on miRNA and mRNA expression profiles of genes known to be associated with PE in villous 3A first trimester trophoblast cells. Cells were exposed to H2O2 at 10 different concentrations (0-1 mM) for 0.5, 4, 24, and 48 h. Cytotoxicity was determined using the SRB assay and data was used to calculate the IC50 of H2O2. Total RNA was extracted after short-term exposure (4 h) to H2O2 for miRNA expression profiling. H2O2 exerted a concentration and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2 (5% of IC50) significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluatable miRNAs. Short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2 significantly alters miRNA profile. Oxidative stress plays a crucial role in preeclampsia (PE) pathogenesis. Evidence indicates altered microRNAs (miRNAs) expression in PE, however, the relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in PE is not fully elucidated. In the present study, we investigate the impact of increased oxidative stress on miRNA and mRNA expression profiles of genes known to be associated with PE in villous 3A first trimester trophoblast cells. Cells were exposed to H2O2 at 10 different concentrations (0-1 mM) for 0.5, 4, 24, and 48 h. Cytotoxicity was determined using the SRB assay and data was used to calculate the IC50 of H2O2. Total RNA was extracted after short-term exposure (4 h) to H2O2 for miRNA expression profiling. H2O2 exerted a concentration and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2 (5% of IC50) significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluatable miRNAs. Short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2 significantly alters miRNA profile. Cells were grown to 90% confluency in 75 cm2 flasks and exposed to 25 ÂµM H2O2 in complete medium for 4 h. Total RNA was isolated using the Qiagen miRNEasy Mini Kit and quality/quantity measured in the Molecular Genomics Core at UTMB. RNA was quantitated spectrophotometrically using a NanoDrop ND-1000 (NanoDrop Techniologies, DE). Quality of the purified RNA was assessed by visualization of 18S and 28S RNA bands using an Agilent BioAnalyzer 2100 (Agilent Technologies, CA). Resulting electroperograms were used in the calculation of the 28S/18S ratio and the RNA Integrity Number. Reverse transcription was carried out using either the miScript II RT kit or RT2 First Strand and subsequent SYBR green based real-time PCR on a BioRad Chromo4 Real-Time PCR Detector per manufacturerâs recommendation. The miRNA profile screening was performed using miScript Human miRNome PCR Array (MIHS-3216Z, Qiagen, Valencia, CA). Data was analyzed using the ÎÎCT method with the miScript miRNA PCR Array Data Analysis version 3.5 (SABiosciences, Valencia CA).

Dataset Information

Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

Publications

Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets