Objective  To investigate the effects of prenatal dexamethasone exposure (PDE) on mitochondrial functional homeostasis of placental cells and placental development.

Methods  The PDE rat model was established. The different dose intervention groups were given subcutaneous injections of dexamethasone at 0.2, 0.4 and 0.8 mg/kg/d on days 9~21 of pregnancy, while a control group was established with saline injection. Pregnant rats were executed on the 22nd day of gestation and placental tissues were collected. The mRNA expression of placental cell proliferation and apoptosis indexes and mitochondrial dynamics indexes were detected by qRT-PCR. Transmission electron microscopy was used to observe the ultrastructural changes of placental tissue cells. Relevant kits were used to detect ATP content and reactive oxygen species (ROS) content. qRT-PCR and Western blotting were used to detect autophagy-related gene mRNA and protein expression.

Results  Compared with the control group, the mRNA expression of proliferation gene Ki67 was decreased and the mRNA expression of apoptosis gene Bax was increased in the placenta of rat in the high-dose group. The morphology of mitochondria was abnormal with structure destruction and autophagosome increased. The fluorescence staining intensity of ROS increased. Compared with female offspring, ATP content decreased more significantly in the placenta tissue of male offspring, and the mRNA and protein levels of autophagy related genes LC3II/LC3I and Beclin 1 were significantly increased, while the mRNA and protein expressions of P62 were decreased.

Conclusion  PDE can lead to increased placental mitochondrial division and imbalance of mitochondrial homeostasis (reduction of ATP content, accumulation of ROS, structural disruption, and occurrence of autophagy), which is more pronounced especially in males, and may be the mechanisms of reduced placental cell proliferation and increased apoptosis.

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