Page 135 - GPD-3-2

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Association between dietary soy prevention

of fetal alcohol spectrum disorder and
normalization of placental insulin and

insulin-like growth factor signaling networks and
downstream effector molecule expression

1,3
Fusun Gundogan 1,2 , Ming Tong , and Suzanne M. de la Monte 1,2,3,4 *
1 Department of Pathology and Laboratory Medicine, The Warren Alpert Medical School of Brown
University, Providence, Rhode Island, United States of America
2 Department of Pathology and Laboratory Medicine, Women and Infants Hospital of Rhode Island,
Providence, Rhode Island, United States of America
3 Liver Research Center, Department of Medicine, Rhode Island Hospital, Providence, Rhode Island,
United States of America
4 Departments of Pathology and Laboratory Medicine, Neurology, and Neurosurgery, Rhode Island
Hospital, Providence, Rhode Island, United States of America

Abstract

Chronic prenatal alcohol exposure causes fetal alcohol spectrum disorder (FASD),
often associated with impaired placentation and intrauterine growth restriction.
*Corresponding author:
Suzanne M. de la Monte Ethanol’s inhibition of insulin and insulin-like growth factor Type 1 (IGF-1) signaling
(Suzanne_DeLaMonte_MD@ compromises trophoblastic cell motility and maternal vascular transformation at the
Brown.edu) implantation site. Previous studies have demonstrated that dietary soy effectively
Citation: Gundogan F, Tong M, normalizes placentation and fetal growth in an experimental model of FASD. The
de la Monte SM. Association studies were extended to better understand the mechanisms underlying soy’s
between dietary soy prevention
of fetal alcohol spectrum disorder beneficial effects. Pregnant Long Evans rats were pair-fed with isocaloric liquid
and normalization of placental diets containing either 0% or 36% caloric ethanol from gestation day (GD) 6. The
insulin and insulin-like growth factor protein source in the diets consisted of either casein (standard and control) or soy
signaling networks and downstream
effector molecule expression. Gene isolate. On GD19, placentas were harvested to measure mRNA levels corresponding
Protein Dis. 2024;3(2):3113. to major components of the insulin/IGF-1 pathway, as well as aspartyl-asparaginyl-
doi: 10.36922/gpd.3113 β-hydroxylase (ASPH), Notch, and HES, which play critical roles in placentation.
Received: March 7, 2024 Chronic gestational ethanol exposure in rats fed diets containing casein significantly
Accepted: April 7, 2024 reduced the expression of insulin, insulin receptor, Igf1, IGF-1 receptor (Igf1r), insulin
Published Online: June 13, 2024 receptor substrate Type 1 (Irs1), Irs2, Asph, and Hes1. In addition, ethanol significantly
Copyright: © 2024 Author(s). decreased ASPH protein expression. Dietary soy mitigated most of these effects and
This is an Open Access article further enhanced signaling by upregulating Igf2, Igf2r, Irs1, Irs2, Irs4, Notch, and Hes1
distributed under the terms of the
Creative Commons Attribution in rats chronically exposed to ethanol relative to corresponding control samples. The
License, permitting distribution, protective effects of dietary soy in FASD act at the mRNA level and positively impact
and reproduction in any medium, pathways imperative for normal placentation and fetal development. Gestational
provided the original work is
properly cited. dietary soy may provide an effective means of preventing FASD in vulnerable
populations.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Aspartyl-asparaginyl-β-hydroxylase; Notch; mRNA; Polymerase chain reaction
affiliations.

Volume 3 Issue 2 (2024) 1 doi: 10.36922/gpd.3113