Antioxidant treatment attenuates age-related placenta GLUT-1 and PLIN-2 downregulation.

BACKGROUND AND AIM: Pregnancy after the age of 35 is correlated with an increased risk of impaired placentation and the development of pregnancy-associated complications. Changes in uterine redox balance seem to play a role in these settings. In this work, we hypothesized that local redox dysregulation impacts the placenta metabolic profile. Thus, we aimed to study the expression of enzymes/transporters related to nutrient uptake during reproductive aging and the effect of antioxidant supplementation.

METHODS

Placenta samples were collected from pregnant women aged between 22 and 41 years, and from mice of different reproductive ages (8-12 and 38-42 weeks). A subgroup of 38-42 weeks-old mice was treated with apocynin (5 mM) in the drinking water. Real-time PCR was carried out to assess gene expression, and immunohistochemistry or western blotting to assess protein expression.

RESULTS

A significant age-related decrease in the expression of glucose transporter type 1 (GLUT-1) was observed in both species. Regarding lipid metabolism, there was a strong negative and significant correlation between the gene expression of fatty-acid transporter type 4 and maternal age, in the human placenta. Perilipin isoform 2 (PLIN-2) decreased significantly with maternal age, in both models. Additionally, a significant age-related decrease in the gene expression of large neutral amino acid transporter type 4 with reproductive age was observed in the mice placenta. Supplementation with apocynin attenuated the observed alterations in GLUT-1 and PLIN-2. The observed changes suggest an age-related placenta metabolic dysfunction, likely associated with oxidative stress, that may negatively impact fetal and placental development.