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Prenatal alcohol exposure contributes to negative pregnancy outcomes by altering fetal vascular dynamics and the placental transcriptome
Author(s) -
Pinson Marisa R.,
Tseng Alexander M.,
Adams Amy,
Lehman Tenley E.,
Chung Karen,
Gutierrez Jessica,
Larin Kirill V.,
Chambers Christina,
Miranda Rajesh C.
Publication year - 2022
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14846
Subject(s) - fetus , placenta , umbilical cord , pregnancy , intrauterine growth restriction , transcriptome , biology , gestation , in utero , fetal circulation , endocrinology , placental circulation , andrology , medicine , physiology , gene expression , anatomy , gene , genetics , biochemistry
Background Prenatal alcohol exposure (PAE) has been shown to alter fetal blood flow in utero and is also associated with placental insufficiency and intrauterine growth restriction (IUGR), suggesting an underlying connection between perturbed circulation and pregnancy outcomes. Methods Timed‐pregnant C57/BL6NHsd mice, bred in‐house, were exposed by gavage on gestational day 10 (GD10) to ethanol (3 g/kg) or purified water, as a control. Pulse‐wave Doppler ultrasound measurements for umbilical arteries and ascending aorta were obtained post‐gavage (GD12, GD14, GD18) on 2 fetuses/litter. RNA from the non‐decidual (labyrinthine and junctional zone) portion of placentas was isolated and processed for RNA‐seq and subsequent bioinformatic analyses, and the association between transcriptomic changes and fetal phenotypes assessed. Results Exposure to ethanol in pregnant mice on GD10 attenuates umbilical cord blood flow transiently during gestation, and is associated with indices of IUGR, specifically decreased fetal weight and morphometric indices of cranial growth. Moreover, RNA‐seq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of Tet3 , which is associated with spontaneous abortion. Weighted gene co‐expression network analysis (WGCNA) identified erythrocyte differentiation and homeostasis as important pathways associated with improved umbilical cord blood flow as gestation progresses. WGCNA also identified sensory perception of chemical stimulus/odorant and receptor activity as important pathways associated with cranial growth. Conclusion Our data suggest that PAE perturbs the expression of placental genes relevant for placental hematopoiesis and environmental sensing, resulting in transient impairment of umbilical cord blood flow and, subsequently, IUGR.