Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension

The American Journal of Pathology
Aiko AokiShigeru Saito

Abstract

Hypertensive disorder of pregnancy (HDP) is a serious pregnancy complication that is life threatening to both the mother and fetus. Understanding HDP pathophysiology is important for developing medical treatments. This study demonstrates the involvement of autophagy deficiency in adverse maternal and fetal outcomes using trophoblast-specific autophagy related (Atg)7, an autophagy-related protein, knockout mice. Atg7 conditional knockout (cKO) placentas were significantly smaller than controls in the spongiotrophoblast layer but not the labyrinth layer, which significantly elevated blood pressure in dams. A marker of autophagy deficiency, sequestosome 1/p62, was accumulated in giant trophoblast cells and in the spongiotrophoblast layer, accompanying increased apoptosis. However, neither proteinuria in dams nor fetal growth restriction was observed. Regarding trophoblast function, the number of trophoblasts migrating into the maternal decidua was significantly reduced, and the wall/lumen ratio of the spiral arteries was significantly increased in cKO placentas, suggesting shallow trophoblast invasion and inadequate vascular remodeling. The relative expression of placental growth factor mRNA was significantly decreased in cKO plac...Continue Reading

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Citations

Jul 4, 2020·American Journal of Reproductive Immunology : AJRI·Jessica SchusterSurendra Sharma
May 13, 2020·International Journal of Molecular Sciences·Akitoshi NakashimaShigeru Saito
May 15, 2019·International Journal of Molecular Sciences·Akitoshi NakashimaShigeru Saito
Jun 27, 2019·International Journal of Molecular Sciences·Ana Cecilia Mestre CitrinovitzAriane Germeyer
Sep 18, 2020·The Journal of Obstetrics and Gynaecology Research·Akitoshi NakashimaShigeru Saito
Nov 25, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shiqin ZhuJinlong Ma
Sep 25, 2020·American Journal of Obstetrics and Gynecology·Anne Cathrine StaffMeryam Sugulle
Feb 15, 2021·Human Immunology·Akitoshi NakashimaShigeru Saito
Mar 7, 2021·International Journal of Molecular Sciences·Akitoshi NakashimaShigeru Saito
Sep 22, 2018·The American Journal of Pathology·Surendra Sharma
Jun 3, 2021·International Journal of Molecular Sciences·Diqi YangYi Ding

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