Estrogen-regulated renal progenitors determine pregnancy adaptation and preeclampsia
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 α 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.
Authors
- Maria Elena Melica (ORCID: https://orcid.org/0000-0002-4599-4083)
- Letizia De Chiara (ORCID: https://orcid.org/0000-0002-8548-2031)
- Ersilia Lucenteforte (ORCID: https://orcid.org/0000-0001-5608-5902)
- Benedetta Mazzinghi (ORCID: https://orcid.org/0000-0003-2809-5622)
- Martin Klaus (ORCID: https://orcid.org/0000-0003-0880-3302)
- Giulia Antonelli (ORCID: https://orcid.org/0000-0002-2555-2130)
- Luigi Cirillo (ORCID: https://orcid.org/0000-0002-0440-7356)
- Paola Romagnani (ORCID: https://orcid.org/0000-0002-1774-8088)
- Carolina Conte (ORCID: https://orcid.org/0000-0002-7679-2935)
- Elena Lazzeri (ORCID: https://orcid.org/0000-0002-9505-2115)
- Claudio Fantini (ORCID: https://orcid.org/0000-0002-9173-0978)
- Giulia Carangelo (ORCID: https://orcid.org/0000-0001-6531-1756)
- Alice Molli (ORCID: https://orcid.org/0009-0009-1040-7983)
- Samuela Landini (ORCID: https://orcid.org/0000-0001-7423-0325)
- Laura Lasagni (ORCID: https://orcid.org/0000-0001-6553-9160)
- Anna Julie Peired (ORCID: https://orcid.org/0000-0001-9732-1369)
- Maria Lucia Angelotti (ORCID: https://orcid.org/0000-0003-3988-7852)
- Valentina Raglianti (ORCID: https://orcid.org/0000-0002-6610-3251)
- Fiammetta Ravaglia (ORCID: https://orcid.org/0000-0001-7121-2324)
- Hans‐Joachim Anders (ORCID: https://orcid.org/0000-0003-2434-2956)
- Tommaso Dafichi
Institutions
- LMU Klinikum (DE)
- Meyer Children's Hospital (IT)
- Hospital of Prato (IT)
- University of Florence (IT)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1126/science.adp4629
- Citations
- 8
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 16.46