Estrogen-regulated renal progenitors determine pregnancy adaptation and preeclampsia

• 成果类型: Article
• 署名作者: Conte, Carolina; Angelotti, Maria Lucia; Mazzinghi, Benedetta; Melica, Maria Elena; Antonelli, Giulia; Carangelo, Giulia; Landini, Samuela; Raglianti, Valentina; Ravaglia, Fiammetta; Cirillo, Luigi; Fantini, Camilla; Dafichi, Tommaso; Klaus, Martin; Lucenteforte, Ersilia; Molli, Alice; De Chiara, Letizia; Peired, Anna Julie; Lazzeri, Elena; Anders, Hans-Joachim; Lasagni, Laura; Romagnani, Paola
• 署名单位: University of Florence; University of Florence; Azienda Ospedaliera Universitaria (AOU) MEYER; University of Munich; University of Florence
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adp4629
• 发表日期: 2025-09-04
• 页码: 1016-1023
• 关键词: PODOCYTE; expression; cells; morphogenesis; disease; MODEL

摘要

The global burden of kidney disease displays marked sexual dimorphism. Lineage tracing and single-cell RNA-sequencing revealed that starting from puberty, estrogen signaling in female mice supports self-renewal and differentiation of renal progenitors to increase filtration capacity, reducing sensitivity to glomerular injury compared with that of males. This phenomenon accelerated as female kidneys adapted to the workload of pregnancy. Deletion of estrogen receptor alpha in renal progenitors disrupted this adaptation, leading to preeclampsia, fetal growth restriction, and increased maternal risk of hypertension and chronic kidney disease. Offspring from affected mothers had fewer nephrons, resulting in early-life hypertension and greater susceptibility to kidney disease. These results highlight the fundamental role of kidney fitness and renal progenitors for pregnancy and preeclampsia and as a determinant of sexual dimorphism in kidney disease.