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Alterations in sperm-inherited noncoding RNAs associate with late-term fetal growth restriction induced by preconception paternal alcohol use.

ABSTRACT: Using a mouse model, our group recently described an association between chronic paternal alcohol use prior to conception and deficits in offspring growth. Here, we sought to determine the impact of alcohol exposure on male reproductive physiology and the association of sperm-inherited noncoding RNAs with the transmission of the observed growth defects. Alcohol exposure did not appreciably alter male reproductive physiology or fertility. However, chronic alcohol use reproducibly induced late-term fetal growth restriction in the offspring, which correlated with a shift in the proportional ratio of transfer RNA-derived small RNAs to Piwi-interacting RNAs, as well as altered enrichment of microRNAs miR21, miR30, and miR142 in alcohol-exposed sperm. Although our dataset share similarities to prior works examining the impact of paternal stress on offspring phenotype, we were unable to identify any changes in plasma corticosterone, indicating alcohol may alter sperm-inherited noncoding RNAs through distinct mechanisms.

SUBMITTER: Bedi Y

PROVIDER: S-EPMC6783280 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Alterations in sperm-inherited noncoding RNAs associate with late-term fetal growth restriction induced by preconception paternal alcohol use.

Bedi Yudhishtar Y Chang Richard C RC Gibbs Rachel R Clement Tracy M TM Golding Michael C MC

Reproductive toxicology (Elmsford, N.Y.) 20190430

Using a mouse model, our group recently described an association between chronic paternal alcohol use prior to conception and deficits in offspring growth. Here, we sought to determine the impact of alcohol exposure on male reproductive physiology and the association of sperm-inherited noncoding RNAs with the transmission of the observed growth defects. Alcohol exposure did not appreciably alter male reproductive physiology or fertility. However, chronic alcohol use reproducibly induced late-ter ...[more]

PMID: 31051257

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Project description:ObjectiveTranscriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs. Approach and Results: Our investigation of over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study-associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation.ConclusionsThese findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.

Project description:Fetal growth restriction (FGR) occurs when the fetus does not reach its genetically programmed intrauterine potential for growth and affects ~5‑10% of pregnancies. This condition is one of the leading causes of perinatal mortality and morbidity associated with obstetric and neonatal complications. Placental dysfunction in FGR causes an impairment in the transfer of nutrients and oxygen from the mother to the developing fetus. Maternal adaptations to placental insufficiency may also play a role in the pathophysiology of FGR. The present study aimed to compare the proteome of the placentas of 18 women with the physiological course of pregnancy and eutrophic fetus [estimated fetal weight (EFW) >10th percentile; control group] and 18 women with late FGR (EFW <10th percentile) diagnosed after 32 weeks of pregnancy, according to the Delphi consensus (study group). The U. Mann‑Whitney test was used to compare two independent groups. The R. Spearman correlation coefficient significance test was used to assess the existence of a relationship between the analyzed measurable parameters. P<0.05 was considered to indicate a statistically significant difference. The tests showed the presence of 356 different proteins which were responsible for the regulation of gene transcription control, inhibiting the activity of proteolytic enzymes, regulation of trophoblast proliferation and angiogenesis and inflammatory response. In the FGR placental proteome, other detected proteins were mostly involved in response to oxidative stress, cellular oxidation and detoxication, apoptosis, hemostatic and catabolic processes, energy transduction protein interactions, cell proliferation, differentiation and intracellular signaling. The present study used chromatographic mass‑spectrometry to compare the placental proteome profiles in pregnancies complicated by late‑onset FGR and normal pregnancy. Comparative analysis of proteomes from normal and FGR placentas showed significant differences. Further research is needed to clarify maternal and fetal adaptations to FGR.

Dataset Information

Alterations in sperm-inherited noncoding RNAs associate with late-term fetal growth restriction induced by preconception paternal alcohol use.

Publications

Alterations in sperm-inherited noncoding RNAs associate with late-term fetal growth restriction induced by preconception paternal alcohol use.

Similar Datasets

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