Nutrient sensor signaling pathways and cellular stress in fetal growth restriction

Bethany Hart, Elizabeth Morgan, Emilyn U. Alejandro

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

Fetal growth restriction is one of the most common obstetrical complications resulting in significant perinatal morbidity and mortality. The most frequent etiology of human singleton fetal growth restriction is placental insufficiency, which occurs secondary to reduced utero-placental perfusion, abnormal placentation, impaired trophoblast invasion and spiral artery remodeling, resulting in altered nutrient and oxygen transport. Two nutrient-sensing proteins involved in placental development and glucose and amino acid transport are mechanistic target of rapamycin (mTOR) and O-linked N-acetylglucosamine transferase (OGT), which are both regulated by availability of oxygen. Impairment in either of these pathways is associated with fetal growth restriction and accompanied by cellular stress in the forms of hypoxia, oxidative and endoplasmic reticulum (ER) stress, metabolic dysfunction and nutrient starvation in the placenta. Recent evidence has emerged regarding the potential impact of nutrient sensors on fetal stress response, which occurs in a sexual dysmorphic manner, indicating a potential element of genetic gender susceptibility to fetal growth restriction. In this mini review, we focus on the known role of mTOR and OGT in placental development, nutrient regulation and response to cellular stress in human fetal growth restriction with supporting evidence from rodent models.

Original languageEnglish (US)
Pages (from-to)R155-R165
JournalJournal of molecular endocrinology
Volume62
Issue number2
DOIs
StatePublished - Feb 2019

Bibliographical note

Funding Information:
This work was supported by the NIH NIDDK (K01DK103823, R03DK114465, R01DK115720, R21DK112144) to E U A.

Keywords

  • Cellular stress
  • Fetal growth restriction
  • MTOR
  • Nutrient sensors
  • Nutrient transport
  • O-GlcNAc transferase (OGT)
  • Placenta
  • Sexual dymorphism

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