Trophoblast-Specific Conditional Atg7 Knockout Mice Develop Gestational Hypertension.

This study demonstrates the involvement of autophagy deficiency in adverse maternal and fetal outcomes utilizing trophoblast-specific Atg7, an autophagy-related protein, knockout mice. Atg7 conditional knockout (cKO) placentas were significantly smaller than controls in the spongiotrophoblast layer but not labyrinth layer, which significantly elevated blood pressure in dams. A marker of autophagy deficiency, SQSTM1/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 to 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 placentas compared with the control, likely causing poor placentation; however, other factors were unchanged in cKO placentas. This is the first report of autophagy deficiency leading to impaired placentation complicated by maternal HDP due to trophoblast dysfunction, and suggests that placental autophagy is required for normal placentation. PMID: 30165042 [PubMed - as supplied by publisher]
Source: Am J Pathol - Category: Pathology Authors: Tags: Am J Pathol Source Type: research