Maternal selenium deficiency suppresses proliferation, induces autophagy dysfunction and apoptosis in the placenta of mice

Abstract

Selenium deficiency is thought to be associated with the occurrence of gestational complications. However, the underlying mechanism of selenium deficiency impairs placental function remains unclear. In this study, female mice were separately supplemented with a Se-deficient (0.02 mg/kg Se) or control diet (0.2 mg/kg Se) for 12 weeks before mating and throughout gestation. Maternal liver and placentas were collected at embryonic day 15.5 and analyzed for Se content. Oxidative stress status, proliferation capability, autophagy, and apoptosis of the placenta were determined. We found that maternal selenium deficiency decreased placental Se concentration and some antioxidant selenoproteins expressions. The concentrations of catalase and glutathione in selenium-deficient placentas were reduced, along with an increase in hydrogen peroxide (H2O2) content. Selenium deficiency inhibited the expression of proliferating cell nuclear antigen. Autophagosomes, autophagolysosomes, and upregulation of autophagy-related protein microtubule-associated protein 1 light chain 3 alpha II (LC3B), Beclin1, PTEN-induced putative kinase 1 (PINK1), and Parkin were found in the selenium-deficient trophoblasts. Autophagic substrate p62/sequestosome 1 was surprisingly increased, indicating autophagy flux dysfunction. Selenium deficiency increased expressions of B cell leukemia/lymphoma 2 associated X protein (Bax), cleaved caspase-9/-3, and decreased the B cell leukemia/lymphoma 2 (Bcl2) level. Moreover, typical apoptotic ultrastructure and apoptosis-positive cells were observed in the selenium-deficient placenta. Our results suggested that maternal selenium deficiency impaired placental proliferation, induced autophagy dysfunction and apoptosis via increasing oxidative stress, and the Akt/mechanistic target of rapamycin (mTOR) pathway involved in this process. This study revealed a novel mechanism by which maternal selenium deficiency caused impairment of the placenta.

Keywords: apoptosis; autophagy; oxidative stress; placenta; proliferation; selenium deficiency.