Irene Martín-EstalInma Castilla-CortázarFabiola Castorena-TorresChapter

First Online: 23 June 2021

Part of the Reviews of Physiology, Biochemistry and Pharmacology book series (REVIEWS, volume 180)Abstract

Alcohol is one of the most consumed drugs in the world, even during pregnancy. Its use is a risk factor for developing adverse outcomes, e.g. fetal death, miscarriage, fetal growth restriction, and premature birth, also resulting in fetal alcohol spectrum disorders. Ethanol metabolism induces an oxidative environment that promotes the oxidation of lipids and proteins, triggers DNA damage, and advocates mitochondrial dysfunction, all of them leading to apoptosis and cellular injury. Several organs are altered due to this harmful behavior, the brain being one of the most affected. Throughout pregnancy, the human placenta is one of the most important organs for women’s health and fetal development, as it secretes numerous hormones necessary for a suitable intrauterine environment. However, our understanding of the human placenta is very limited and even more restricted is the knowledge of the impact of toxic substances in its development and fetal growth. So, could ethanol consumption during this period have wounding effects in the placenta, compromising proper fetal organ development? Several studies have demonstrated that alcohol impairs various signaling cascades within G protein-coupled receptors and tyrosine kinase receptors, mainly through its action on insulin and insulin-like growth factor 1 (IGF-1) signaling pathway. This last cascade is involved in cell proliferation, migration, and differentiation and in placentation. This review tries to examine the current knowledge and gaps in our existing understanding of the ethanol effects in insulin/IGFs signaling pathway, which can explain the mechanism to elucidate the adverse actions of ethanol in the maternal–fetal interface of mammals.

KeywordsAlcohol consumption Fetal growth restriction IGF-1 Oxidative stress Placenta 

AbbreviationsAAH

Aspartyl-asparaginyl β-hydroxylase

ADH

Alcohol dehydrogenase

ALDH

Aldehyde dehydrogenase

ALS

Acid-labile subunit

ARBD

Alcohol-related birth defects

CCM3

Cerebral cavernous malformation protein 3

CNS

Central nervous system

CTCF

CCCTC site binding factor

CYP450

Cytochrome P450 system

CYP2E1

Cytochrome P450 2E1

Dnmt

DNA methyltransferase

ERKs

Extracellular signal-regulated kinases

ETC

Electron transport chain

EtOH

Ethanol

FAS

Fetal alcohol syndrome

FASD

Fetal alcohol spectrum disorders

FGR

Fetal growth restriction

GH

Growth hormone

GHRH

Growth hormone-releasing hormone

GPCRs

G protein-coupled receptors

H2O2

Hydrogen peroxide

ICR

Imprinting control region

IGF-1

Insulin-like growth factor 1

IGF-2

Insulin-like growth factor 2

IGF1R

IGF-1 receptor

IGF2R

IGF-2 receptor

IGFBPs

IGF-1 binding proteins

INSR

Insulin receptor

IRSs

Insulin receptor substrates

JAK

Janus kinases

JNKs

c-Jun N-terminal kinases

MAPKs

Mitogen-activated protein kinases

ND-PAE

Neurobehavioral disorder associated with prenatal alcohol

NO

Nitric oxide

PAS

Placental associated syndromes

PDGF

Platelet-derived growth factor

PI3K

Phosphatidylinositol-3-kinase

PKA

Protein kinase A

PKB

Protein kinase B

PKC

Protein kinase C

PTEN

Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

PTP-1b

Protein-tyrosine phosphatase 1b

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

RTKs

Tyrosine kinase receptors

STATs

Signal transducer and activator of transcription proteins

TGFβ

Transforming growth factor β

VEGFR1

Vascular endothelial growth factor receptor 1

VEGFR2

Vascular endothelial growth factor receptor 2

Inma Castilla-Cortázar and Fabiola Castorena-Torres contributed equally to this work.

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NotesAcknowledgements

The authors would like to express their gratitude to MD. Rodolfo Benavides, MD. Andrea Leal, and MD. Marcela Galindo for their invaluable help.

Conflict of Interest

The authors declare that they have no conflict of interest.

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