Physiological and pathological functions of sphingolipids in pregnancy

Yuliya Fakhr; David N Brindley; Denise G Hemmings

doi:10.1016/j.cellsig.2021.110041

Physiological and pathological functions of sphingolipids in pregnancy

Cell Signal. 2021 Sep:85:110041. doi: 10.1016/j.cellsig.2021.110041. Epub 2021 May 13.

Authors

Yuliya Fakhr¹, David N Brindley², Denise G Hemmings³

Affiliations

¹ Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada.
² Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada; Signal Transduction Research Group, Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2S2, Canada; Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada.
³ Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB T6G 2S2, Canada; Women and Children's Health Research Institute, University of Alberta, Edmonton, AB T6G 1C9, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada; Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB T6G 2S2, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2S2, Canada. Electronic address: denise.hemmings@ualberta.ca.

PMID: 33991614
DOI: 10.1016/j.cellsig.2021.110041

Abstract

Signaling by the bioactive sphingolipid, sphingosine 1-phosphate (S1P), and its precursors are emerging areas in pregnancy research. S1P and ceramide levels increase towards end of gestation, suggesting a physiological role in parturition. However, high levels of circulating S1P and ceramide are correlated with pregnancy disorders such as preeclampsia, gestational diabetes mellitus and intrauterine growth restriction. Expression of placental and decidual enzymes that metabolize S1P and S1P receptors are also dysregulated during pregnancy complications. In this review, we provide an in-depth examination of the signaling mechanism of S1P and ceramide in various reproductive tissues during gestation. These factors determine implantation and early pregnancy success by modulating corpus luteum function from progesterone production to luteolysis through to apoptosis. We also highlight the role of S1P through receptor signaling in inducing decidualization and angiogenesis in the decidua, as well as regulating extravillous trophoblast migration to anchor the placenta into the uterine wall. Recent advances on the role of the S1P:ceramide rheostat in controlling the fate of villous trophoblasts and the role of S1P as a negative regulator of trophoblast syncytialization to a multinucleated placental barrier are discussed. This review also explores the role of S1P in anti-inflammatory and pro-inflammatory signaling, its role as a vasoconstrictor, and the effects of S1P metabolizing enzymes and receptors in pregnancy.

Keywords: Ceramide; Corpus luteum; Decidua; Placenta; Sphingosine 1–phosphate; Trophoblast.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Ceramides
Female
Humans
Lysophospholipids / metabolism
Placenta* / metabolism
Pregnancy
Sphingolipids*
Sphingosine / metabolism
Sphingosine-1-Phosphate Receptors
Trophoblasts / metabolism

Substances

Ceramides
Lysophospholipids
Sphingolipids
Sphingosine-1-Phosphate Receptors
Sphingosine

Abstract

Publication types

MeSH terms

Substances

Grants and funding