Mathiesen Line, Sandal Dea, Hammer Ida Elise Moelgaard, Styrishave Bjarne, Knudsen Lisbeth E
Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen, Denmark.
Toxicology and Drug Metabolism Group, Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70073. doi: 10.1111/bcpt.70073.
Endocrine disruption during pregnancy has gained increasing interest as epidemiological studies report associations of exposures and adverse effects on fetal growth, followed by effects on the growing child and ultimately in the adult. When studying endocrine disruption during pregnancy, the placental steroidogenesis is difficult to model, as the human placenta is unique in the pathway of cellular uptake of cholesterol, the high levels of progesterone production and the expression of aromatase. Models to test for endocrine disruption should respect species differences, with preference to human models for human risk assessment. Here, we present existing research of placental steroidogenesis and other placental hormones using human placental models: placental perfusion, placental explants, fragments, microsomes and vesicles, primary cell culture, stem cells, placenta on a chip and choriocarcinoma cell cultures: BeWo, HTR-8/SVneo, Jar, JEG-3 and ACH-3P. We conclude that there is a lack of research focused on placental steroidogenesis and the effects of endocrine-disrupting compounds. Advantages and limitations of existing models are discussed, and future directions suggested.
随着流行病学研究报告孕期接触内分泌干扰物与对胎儿生长的不良影响之间存在关联，随后是对成长中的儿童乃至成年人产生影响，孕期内分泌干扰问题越来越受到关注。在研究孕期内分泌干扰时，胎盘类固醇生成很难建模，因为人类胎盘在胆固醇细胞摄取途径、高水平孕酮生成以及芳香化酶表达方面具有独特性。用于测试内分泌干扰的模型应考虑物种差异，在进行人类风险评估时优先选择人类模型。在此，我们介绍利用人类胎盘模型对胎盘类固醇生成及其他胎盘激素的现有研究：胎盘灌注、胎盘外植体、片段、微粒体和囊泡、原代细胞培养、干细胞、芯片上的胎盘以及绒毛膜癌细胞培养：BeWo、HTR - 8/SVneo、Jar、JEG - 3和ACH - 3P。我们得出结论，目前缺乏针对胎盘类固醇生成以及内分泌干扰化合物影响的研究。讨论了现有模型的优缺点，并提出了未来的研究方向。
