Martier Ashley T, Maurice Yasmin V, Conrad K Michael, Carlino Delia A, Mauvais-Jarvis Franck, Mondrinos Mark J
Department of Biomedical Engineering, Tulane University School of Science & Engineering, New Orleans, LA, USA.
Tulane Center of Excellence in Sex-based Precision Medicine, New Orleans, LA, USA.
Commun Biol. 2025 Oct 3;8(1):1422. doi: 10.1038/s42003-025-08822-1.
Sex-specific cell culture methods and microphysiological systems can enhance our understanding of how biological sex influences health and disease. Here, we investigated the effects of estradiol and dihydrotestosterone on primary human lung and ocular fibroblasts as well as in human umbilical vein and retinal microvascular endothelial cells from both female and male donors. Treatment of female cells with estradiol and male cells with dihydrotestosterone in 2D culture significantly enhanced proliferation, mitochondrial membrane potential, and upregulated genes associated with bioenergetics and stress responses. Conversely, treatment of female cells with dihydrotestosterone and of male cells with estradiol decreased bioenergetic potential and inhibited cell proliferation. A microphysiological model of bulk tissue vasculogenesis revealed that estradiol enhances vasculogenesis in female tissues and inhibits vasculogenesis in male tissues. Collectively, these findings demonstrate that the sex hormone composition of culture medium significantly influences bioassay readouts in a sex-specific manner.
性别特异性细胞培养方法和微生理系统能够增进我们对生物性别如何影响健康与疾病的理解。在此，我们研究了雌二醇和双氢睾酮对来自女性和男性供体的原代人肺成纤维细胞、眼成纤维细胞以及人脐静脉和视网膜微血管内皮细胞的影响。在二维培养中，用雌二醇处理女性细胞以及用双氢睾酮处理男性细胞显著增强了细胞增殖、线粒体膜电位，并上调了与生物能量学和应激反应相关的基因。相反，用双氢睾酮处理女性细胞以及用雌二醇处理男性细胞则降低了生物能量潜力并抑制了细胞增殖。一个大块组织血管生成的微生理模型显示，雌二醇增强女性组织中的血管生成，而抑制男性组织中的血管生成。总体而言，这些发现表明培养基中的性激素组成以性别特异性方式显著影响生物测定读数。
