Abstract
Fetal undernutrition programs cardiometabolic diseases, with higher susceptibility in males. The mechanisms implicated are not fully understood and may be related to sex differences in placental adaptation. To evaluate this hypothesis, we investigated placental oxidative balance, vascularization, glucocorticoid barrier, and fetal growth in rats exposed to 50% global nutrient restriction from gestation day 11 (MUN, n = 8) and controls (n = 8). At gestation day 20 (G20), we analyzed maternal, placental, and fetal weights; oxidative damage, antioxidants, corticosterone, and PlGF (placental growth factor, spectrophotometry); and VEGF (vascular endothelial growth factor), 11β-HSD2, p22phox, XO, SOD1, SOD2, SOD3, catalase, and UCP2 expression (Western blot). Compared with controls, MUN dams exhibited lower weight and plasma proteins and higher corticosterone and catalase without oxidative damage. Control male fetuses were larger than female fetuses. MUN males had higher plasma corticosterone and were smaller than control males, but had similar weight than MUN females. MUN male placenta showed higher XO and lower 11β-HSD2, VEGF, SOD2, catalase, UCP2, and feto-placental ratio than controls. MUN females had similar feto-placental ratio and plasma corticosterone than controls. Female placenta expressed lower XO, 11β-HSD2, and SOD3; similar VEGF, SOD1, SOD2, and UCP2; and higher catalase than controls, being 11β-HSD2 and VEGF higher compared to MUN males. Male placenta has worse adaptation to undernutrition with lower efficiency, associated with oxidative disbalance and reduced vascularization and glucocorticoid barrier. Glucocorticoids and low nutrients may both contribute to programming in MUN males.
Highlights
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To determine whether placental vascularization could be altered by maternal suboptimal nutrition, we examined the Placental Growth Factor (PlGF) level and Vascular Endothelial Growth Factor (VEGF) protein expression
We hypothesized that plasticity of the placenta in response to maternal undernutrition exhibits a sexual dimorphic pattern and can modulate fetal programming
Summary
At G20, maternal total weight and net weight (without conceptus) were significantly lower in MUN compared with those in the control group (Figure 1a,b; p-value < 0.0001; p-value = 0.048). MUN maternal plasma showed lower protein content compared with control, without significant difference in glycemia (Figure 1c,d; p-value = 0.016; p = 0.504). Maternal plasma corticosterone was significantly higher in MUN compared with that in control dams (Figure 1e; p-value = 0.035)
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