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Published on: August 2, 2017
Sex Differences in Placental Protein Expression and Efficiency in a Rat Model of Fetal Programming Induced by
Sophida Phuthong1,2, Cynthia Guadalupe Reyes-Hernández1,3, Pilar Rodríguez-Rodríguez1
1Department of Physiology, Faculty of Medicine, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 2, 28029 Madrid, Spain.
Insights
Fetal undernutrition impairs male placental adaptation, increasing cardiometabolic disease risk. Male placentas showed oxidative imbalance, reduced vascularization, and a weaker glucocorticoid barrier compared to controls.
Area of Science:
- Reproductive Biology
- Developmental Programming
- Endocrinology
Background:
- Fetal undernutrition is linked to cardiometabolic diseases later in life.
- Males exhibit higher susceptibility to these programming effects.
- Sex differences in placental adaptation may underlie these disparities.
Purpose of the Study:
- To investigate placental oxidative balance, vascularization, and glucocorticoid barrier.
- To assess the impact of nutrient restriction on fetal growth and placental function.
- To evaluate sex-specific placental adaptations to maternal undernutrition.
Main Methods:
- Rats underwent 50% global nutrient restriction from day 11 of gestation.
- Placental and fetal tissues were analyzed at day 20 of gestation.
- Measurements included weights, oxidative stress markers, antioxidant enzymes, corticosterone, and protein expression (VEGF, 11β-HSD2, etc.).
Main Results:
- Undernourished dams had lower weight and plasma proteins but higher corticosterone.
- Male fetuses exposed to undernutrition were smaller and had higher corticosterone.
- Male placentas showed increased oxidative stress (XO) and reduced vascularization (VEGF) and glucocorticoid barrier (11β-HSD2) compared to controls.
Conclusions:
- Male placentas exhibit poorer adaptation to nutrient restriction, with oxidative imbalance and reduced vascularization.
- Impaired placental function in males is associated with reduced efficiency and a compromised glucocorticoid barrier.
- Both glucocorticoids and nutrient scarcity likely contribute to programming cardiometabolic risks in undernourished males.
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.
