Page 136 - GPD-3-2

Gene & Protein in Disease Placenta, FASD, and soy

1. Introduction along these lines have yielded promising results, suggesting
the potential of soy-based interventions to mitigate
Fetal alcohol spectrum disorder (FASD) is a significant neurodevelopmental deficits associated with FASD. 21-23 In
public health concern, driven by socioeconomic, mental a comprehensive model of FASD, dietary soy was found
health, and cultural disparities that contribute to heavy to effectively mitigate alcohol-mediated impairments in
alcohol consumption during pregnancy. In addition to placentation and neurodevelopmental features. However,
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characteristic craniofacial abnormalities, FASD features further mechanistic research is warranted to elucidate the
birth and neurodevelopmental defects, intrauterine growth underlying mechanisms and inform future clinical and
restrictions (IUGR), postnatal growth limitations, and population-based applications. The present study builds
increased fetal mortality rates. Placentation, encompassing on our earlier efforts by examining the effects of alcohol
placental maturation, growth, and implantation, is and dietary soy on the mRNA expression of upstream
integral for optimizing the fetal environment, ensuring insulin/IGF signaling pathway molecules, including Asph,
ample nutrient delivery and waste product removal. The Notch1, and Hes1. This investigation aims to assess the
occurrence and severity of FASD are partially rooted degree to which dietary soy mediates its protective effects
in placental dysfunction, mediated by impairments in on placentation at the mRNA level by modulating gene
placentation. Previous studies have established a link expression.
between FASD-mediated impairments in placentation
and reduced signaling through insulin and insulin-like 2. Materials and methods
growth factor (IGF) pathways. These pathways regulate
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the expression and function of aspartyl-asparaginyl- 2.1. Materials
β-hydroxylase (ASPH), which plays critical roles in Qiazol reagent, EZ1 RNA universal tissue kit, QuantiTect
regulating cell motility and invasion necessary for effective SYBR Green polymerase chain reaction (PCR) master mix,
placentation. Heavy alcohol consumption during and the BIO Robot Z1 were procured from Qiagen Sciences
2-5
pregnancy compromises ASPH’s functions, leading to Inc (USA). The AMV first strand cDNA synthesis kit was
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disruptions in critical cellular processes. Mechanistically, obtained from Roche Diagnostics Corporation (USA).
ASPH catalytically hydroxylates and activates Notch, Enzyme-linked immunosorbent assay (ELISA) plates and
7,8
which, in turn, upregulates transcription of hairy and the ELISA plate washer were sourced from Thermo Scientific
7,9
enhancer of split-1 (HES1). Notch is pivotal in regulating Nunc (USA). Horseradish peroxidase (HRP)-conjugated
a broad array of cellular functions during development, secondary antibodies and the soluble fluorophore (Amplex
including growth, motility, and maturation. The Red) were supplied by Invitrogen (USA).
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inhibitory effects of ethanol have been well-documented. 9
2.2. In utero ethanol exposure model
Potential preventive and treatment measures for FASD
should take into consideration the intricate interactions The Lifespan Institutional Animal Care and Use
among maternal factors, placental reactions, and the Committee (IACUC) of Rhode Island Hospital approved
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diverse fetal responses. Addressing problems arising the experimental use and treatment of Long Evans rats for
from insulin/IGF resistance due to impaired signal this research. On gestation day (GD) 6, following timed
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transduction presents a promising avenue. Earlier research mating as previously described, we initiated feeding
has demonstrated the efficacy of peroxisome-proliferator- with isocaloric liquid diets (BioServ, USA). Control diets
activated receptor (PPAR) agonists in preventing or contained 0% ethanol. The experimental diets comprised
reducing the disease-related effects of dysregulated 36% caloric ethanol or 8.2% vol/vol. The protein sources
insulin/IGF signaling in experimental models of consisted of either 100% casein, which was considered a
chronic alcohol exposure, obesity, or nitrosamine control due to its standard inclusion in rodent diets, or
administration. 12-17 PPAR agonists act by bypassing 100% organic soy protein isolate, which was considered
poorly responsive cell surface receptors and stimulating an experimental. Consequently, four study groups were
gene expression at the level of transcription within designated as follows: (i) CC for control-casein, wherein
the nucleus. 18,19 However, practical and health-related the rats were fed ethanol-free diets with casein as the
uncertainties regarding the administration of PPAR agonist protein source; (ii) CS, corresponding to ethanol-free diets
medications to pregnant women warrant exploration with soy as the protein source; (iii) EC, in which the rats
into alternative approaches. Investigating whether the were fed ethanol-containing diets with casein as the protein
insulin-sensitizing effects of natural products, such as soy source; and (iv) ES, corresponding to ethanol-containing
or bioactive isoflavones (daidzein and genistein), could diets with soy as the sole protein source. Eight placentas
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counteract the adverse effects of developmental alcohol were randomly selected from each group for analysis. GD6
exposures is of particular interest. Recent experiments was selected as the start time for ethanol feeding because

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