肥胖已成为全球性的健康挑战，也影响生殖健康。在孕妇中，肥胖会增加并发症的风险，例如早产、巨大儿、妊娠糖尿病和妊娠前期高血压症。此外，肥胖还与新生儿长期不良影响相关，包括心血管和代谢疾病以及神经发育障碍的风险增加。胎盘功能对妊娠结果至关重要，然而背后的机制尚不清楚。转运蛋白P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）对内源性物质如脂质和组织成熟的关键激素皮质醇的胎盘跨膜转运很重要，同时也具有保护作用，可保护胎儿免受外源性物质（如药品）的影响。动物研究表明，母体营养状况可能会影响胎盘转运蛋白的表达，但关于其在人类胎盘上的影响尤其是在早期妊娠期间的影响还知之甚少。在此，我们研究了孕妇超重和肥胖是否会改变ABC编码P-gp或ABCG2编码BCRP的mRNA在人类胎盘第一孕期时的表达情况。得到了75个志愿者在怀孕12周以下自愿行手术流产的第一孕期胎盘样本（批准号：20060063）。绒毛样本（平均孕龄9.35周）用于qPCR分析。对于一部分样本（n = 38），额外的绒毛被快速冷冻用于蛋白质分析。母体BMI是在妊娠终止时定义的。与BMI为18.5-24.9 kg/m2的女性（n = 34）相比，超重（BMI 25-29.9 kg/m2，n = 18）和肥胖女性（BMI≥30 kg/m2，n = 23）的胎盘样本中，ABCB1 mRNA的表达显著增加（p = 0.040和p = 0.003）。虽然P-gp表达在组间没有统计学差异，但BMI增加对男女怀孕的影响相同。为了确定P-gp的表达增加是否得到了补偿，我们测定了ABCG2的表达情况，发现其不受母体肥胖的影响（p = 0.291）。母体BMI会影响人类胎盘第一孕期的ABCB1 mRNA表达，但不会影响ABCG2 mRNA的表达。需要进一步研究早期胎盘功能，以了解母体营养状况等因素如何调节胎盘转运蛋白的表达，并确定其对胎盘-胎儿相互作用的潜在影响。 ©2023年作者。

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.© 2023. The Author(s).