Published In
Biology of Reproduction
Document Type
Pre-Print
Publication Date
1-18-2021
Subjects
Genes -- Research, Microorganisms -- Genetic aspects
Abstract
Abnormally increased angiotensin II activity related to maternal angiotensinogen (AGT) genetic variants, or aberrant receptor activation, is associated with small-for-gestational-age (SGA) babies and abnormal uterine spiral artery remodeling in humans. Our group studies a murine AGT gene titration transgenic (TG; 3-copies of the AGT gene) model, which has a 20% increase in AGT expression mimicking a common human AGT genetic variant (A[-6]G) associated with intrauterine growth restriction (IUGR) and spiral artery pathology. We hypothesized that aberrant maternal AGT expression impacts pregnancy-induced uterine spiral artery angiogenesis in this mouse model leading to IUGR. We controlled for fetal sex and fetal genotype (e.g., only 2-copy wild-type [WT] progeny from WT and TG dams were included). Uteroplacental samples from WT and TG dams from early (days 6.5 and 8.5), mid (d12.5), and late (d16.5) gestation were studied to assess uterine natural killer cell (uNK) phenotypes, decidual metrial triangle angiogenic factors, placental growth and capillary density, placental transcriptomics, and placental nutrient transport. Spiral artery architecture was evaluated at day 16.5 by contrast-perfused three-dimensional micro-computed tomography (3D microCT). Our results suggest that uteroplacental angiogenesis is significantly reduced in TG dams at day 16.5. Males from TG dams are associated with significantly reduced uteroplacental angiogenesis from early to late gestation compared with their female littermates and WT controls. Angiogenesis was not different between fetal sexes from WT dams. We conclude that male fetal sex compounds the pathologic impact of maternal genotype in this mouse model of growth restriction.
Rights
Copyright © 2021 BioOne
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DOI
10.1093/biolre/ioab006
Persistent Identifier
https://archives.pdx.edu/ds/psu/35206
Citation Details
Hebert, Jessica F.; Millar, Jess A.; Raghavan, Rahul; Romney, Amie L.; Podrabsky, Jason; Rennie, Monique Y.; Felker, Allison; O'Tierney-Ginn, Perrie; Morita, Mayu; DuPriest, Elizabeth A.; and Morgan, Terry K., "Male Fetal Sex Affects Uteroplacental Angiogenesis in Growth Restriction Mouse Model" (2021). Biology Faculty Publications and Presentations. 337.
https://archives.pdx.edu/ds/psu/35206
Description
This is the author’s version of a work. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biology of Reproduction, Volume 104, Issue 4, April 2021, Pages 924–934.