ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese
Signe Justesen1, Katrine Bilde1, Rasmus H Olesen1,2
1Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus C, Denmark.
Insights
Maternal obesity significantly increases ABCB1 mRNA expression, which encodes P-glycoprotein (P-gp), in early human placenta. Breast Cancer Resistance Protein (BCRP) expression remains unaffected, suggesting altered placental transport in overweight and obese pregnancies.
Area of Science:
- Reproductive biology and developmental toxicology
- Maternal-fetal medicine
- Pharmacogenetics and molecular biology
Background:
- Obesity is a global health issue with significant implications for reproductive health and pregnancy outcomes.
- Placental transporter proteins, P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP), are crucial for fetal protection and nutrient/hormone transport.
- Maternal nutritional status may influence placental transporter expression, but data on early human pregnancy is limited.
Purpose of the Study:
- To investigate the impact of maternal overweight and obesity on the mRNA expression of ABCB1 (P-gp) and ABCG2 (BCRP) in first-trimester human placenta.
- To explore early placental adaptations in response to maternal body mass index (BMI).
Main Methods:
- Quantitative PCR (qPCR) was used to analyze ABCB1 and ABCG2 mRNA expression in 75 first-trimester placental villous samples (gestational age < 12 weeks).
- Maternal Body Mass Index (BMI) was categorized according to WHO standards.
- Protein analysis was performed on a subset of samples (n=38).
Main Results:
- ABCB1 mRNA expression was significantly elevated in placentas from overweight (BMI 25-29.9 kg/m²) and obese (BMI ≥ 30 kg/m²) women compared to normal weight women (BMI 18.5-24.9 kg/m²).
- ABCG2 mRNA expression was not significantly affected by maternal BMI.
- The observed increase in ABCB1 mRNA expression was consistent across male and female pregnancies.
Conclusions:
- Maternal BMI significantly influences ABCB1 mRNA expression in the first-trimester human placenta, indicating altered P-gp levels early in pregnancy.
- ABCG2 (BCRP) mRNA expression appears unaffected by maternal obesity in early pregnancy.
- Further research is needed to elucidate the mechanisms regulating placental transporter expression by maternal factors and its consequences for placental-fetal interactions.
Abstract:
Obesity has become a global health challenge also affecting reproductive health. In pregnant women, obesity increases the risk of complications such as preterm birth, macrosomia, gestational diabetes, and preeclampsia. Moreover, obesity is associated with long-term adverse effects for the offspring, including increased risk of cardiovascular and metabolic diseases and neurodevelopmental difficulties. The underlying mechanisms are far from understood, but placental function is essential for pregnancy outcome. Transporter proteins P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are important for trans-placental transport of endogenous substances like lipids and cortisol, a key hormone in tissue maturation. They also hold a protective function protecting the fetus from xenobiotics (e.g. pharmaceuticals). Animal studies suggest that maternal nutritional status can affect expression of placental transporters, but little is known about the effect on the human placenta, especially in early pregnancy. Here, we investigated if overweight and obesity in pregnant women altered mRNA expression of ABCB1 encoding P-gp or ABCG2 encoding BCRP in first trimester human placenta. With informed consent, 75 first trimester placental samples were obtained from women voluntarily seeking surgical abortion (< gestational week 12) (approval no.: 20060063). Villous samples (average gestational age 9.35 weeks) were used for qPCR analysis. For a subset (n = 38), additional villi were snap-frozen for protein analysis. Maternal BMI was defined at the time of termination of pregnancy. Compared to women with BMI 18.5-24.9 kg/m2 (n = 34), ABCB1 mRNA expression was significantly increased in placenta samples from women classified as overweight (BMI 25-29.9 kg/m2, n = 18) (p = 0.040) and women classified as obese (BMI ≥ 30 kg/m2, n = 23) (p = 0.003). Albeit P-gp expression did not show statistically significant difference between groups, the effect of increasing BMI was the same in male and female pregnancies. To investigate if the P-gp increase was compensated, we determined the expression of ABCG2 which was unaffected by maternal obesity (p = 0.291). Maternal BMI affects ABCB1 but not ABCG2 mRNA expression in first trimester human placenta. Further studies of early placental function are needed to understand how the expression of placental transport proteins is regulated by maternal factors such as nutritional status and determine the potential consequences for placental-fetal interaction.
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