Preeclampsia impedes foetal kidney development by delivering placenta-derived exosomes to glomerular endothelial cells.

Foetal renal dysplasia is still the main cause of adult renal disease. Placenta-derived exosomes are an important communication tool, and they may play an important role in placental (both foetal and maternal) function. We hypothesize that in women with preeclampsia, foetal renal dysplasia is impeded by delivering placenta-derived exosomes to glomerular endothelial cells. In the present study, we established a PE trophoblast oxidative stress model to isolate exosomes from supernatants by ultracentrifugation (NO-exo and H/R-exo) and collected normal and PE umbilical cord blood plasma to isolate exosomes by ultracentrifugation combined with sucrose density gradient centrifugation (N-exo and PE-exo), then we investigated their effects on foetal kidney development by in vitro, ex vivo and in vivo models. The PE trophoblast oxidative stress model was established successfully. After that, in in vitro studies, we found that H/R-exo and PE-exo could adversely affect glomerular endothelial cell proliferation, tubular formation, migration, and barrier functions. In ex vivo studies, H/R-exo and PE-exo both inhibited the growth and branch formation of kidney explants, along with the decrease of VE-cadherin and Occludin. In in vivo studies, we also found that H/R-exo and PE-exo could result in renal dysplasia, reduced glomerular number, and reduced barrier function in foetal mice. In conclusion, we demonstrated that PE placenta-derived exosomes could lead to foetal renal dysplasia by delivering placenta-derived exosomes to foetal glomerular endothelial cells, which provides a novel understanding of the pathogenesis of foetal renal dysplasia. Video Abstract. © 2023. The Author(s).

Citation

Mengqi Gu, Pengzheng Chen, Dongmei Zeng, Xiaotong Jiang, Qingfeng Lv, Yuchen Li, Fengyuan Zhang, Shuting Wan, Qian Zhou, Yuan Lu, Xietong Wang, Lei Li. Preeclampsia impedes foetal kidney development by delivering placenta-derived exosomes to glomerular endothelial cells. Cell communication and signaling : CCS. 2023 Nov 23;21(1):336

Mesh Tags

PMID: 37996949

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