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Maternal and fetal alkaline ceramidase 2 is required for placental vascular integrity in mice.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Nov; Vol. 34 (11), pp. 15252-15268. Date of Electronic Publication: 2020 Sep 22. - Publication Year :
- 2020
-
Abstract
- Sphingolipids have been implicated in mammalian placental development and function, but their regulation in the placenta remains unclear. Herein we report that alkaline ceramidase 2 (ACER2) plays a key role in sustaining the integrity of the placental vasculature by regulating the homeostasis of sphingolipids in mice. The mouse alkaline ceramidase 2 gene (Acer2) is highly expressed in the placenta between embryonic day (E) 9.5 and E12.5. Acer2 deficiency in both the mother and fetus decreases the placental levels of sphingolipids, including sphingoid bases (sphingosine and dihydrosphingosine) and sphingoid base-1-phosphates (sphingosine-1-phosphate and dihydrosphingosine-1-phosphate) and results in the in utero death of ≈50% of embryos at E12.5 whereas Acer2 deficiency in either the mother or fetus has no such effects. Acer2 deficiency causes hemorrhages from the maternal vasculature in the junctional and/or labyrinthine zones in E12.5 placentas. Moreover, hemorrhagic but not non-hemorrhagic Acer2-deficient placentas exhibit an expansion of parietal trophoblast giant cells with a concomitant decrease in the area of the fetal blood vessel network in the labyrinthine zone, suggesting that Acer2 deficiency results in embryonic lethality due to the atrophy of the fetal blood vessel network in the placenta. Taken together, these results suggest that ACER2 sustains the integrity of the placental vasculature by controlling the homeostasis of sphingolipids in mice.<br /> (© 2020 Federation of American Societies for Experimental Biology.)
- Subjects :
- Animals
Female
Hemorrhage etiology
Hemorrhage metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Placenta metabolism
Pregnancy
Sphingosine metabolism
Vascular Diseases etiology
Vascular Diseases metabolism
Alkaline Ceramidase physiology
Hemorrhage pathology
Lysophospholipids metabolism
Placenta pathology
Sphingolipids metabolism
Sphingosine analogs & derivatives
Vascular Diseases pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 34
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 32959379
- Full Text :
- https://doi.org/10.1096/fj.202001104R