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Antioxidant treatment attenuates age-related placenta GLUT-1 and PLIN-2 downregulation
Ana Rita Pinheiro1, Adriana Raquel Rodrigues2, Liliana Matos2
1Unidade de Biologia Experimental, Departamento de Biomedicina, Faculdade de Medicina, Universidade do Porto, Rua Dr. Plácido da Costa, S/N, 4200 - 450, Porto, Portugal; Ageing and Stress Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
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.
