Sex differences in long-term kidney fibrosis following neonatal nephron loss during ongoing nephrogenesis

Molecular and Cellular Pediatrics

Research

Nada Cordasic¹  Karl F. Hilgers¹  Carlos Menendez-Castro²  Andrea Hartner²  Joachim Woelfle²  Fabian B. Fahlbusch³ 

[1] Department of Nephrology and Hypertension, University Hospital of Erlangen, Erlangen, Germany;Department of Pediatrics and Adolescent Medicine, University Hospital of Erlangen, Erlangen, Germany;Division of Neonatology and Pediatric Intensive Care Medicine, University Hospital of Erlangen, Erlangen, Germany;

关键词: Sex differences;    Kidney fibrosis;    Neonatal nephron loss;    Nephrogenesis;    Neonatal uninephrectomy;   

DOI  :  10.1186/s40348-023-00164-4

 received in 2023-05-14, accepted in 2023-08-14,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundClinical studies suggest that female sex plays a protective role in the development and progression of kidney disease. Recent experimental studies indicate that in male rats early nephron loss under ongoing nephrogenesis is accompanied by severe long-term sequelae. In humans, nephron formation occurs mainly in the third trimester, ceasing with 36 weeks of gestation. Due to perinatal complications, preterm infants delivered during this vulnerable period may undergo acute nephron loss. In rats nephrogenesis persists until postnatal day 10, reflecting the situation of human preterms with persisting nephrogenesis. In our animal model of neonatal uninephrectomy, female and male rats were uninephrectomized at day 1 of life. Hypothesizing sex-dependent differences, long-term renal outcome was assessed after 1 year.ResultsIn both sexes, neonatal uninephrectomy was not followed by arterial hypertension at 1 year of age. Compensatory weight gain and glomerular hypertrophy of the remaining kidney occurred in uninephrectomized female and male animals. Selected markers of interstitial inflammation and fibrosis were regulated sex-dependently. The expression of monocyte chemoattractant protein-1 was increased in females, while tubulointerstitial infiltration by M1 macrophages was significantly higher in males after neonatal uninephrectomy. Neonatally uninephrectomized male rats had more glomerulosclerosis and podocyte damage compared to females, which was assessed by a semiquantitative score and desmin staining. RT-PCR revealed that after neonatal uninephrectomy in the remaining contralateral kidney of female rats the expression of candidate genes of renal development and function, i.e., wt-1, nephrin, synaptopodin, gdnf, and itga8 was higher than in males.ConclusionsBased on these observations we conclude that female sex is protective in the long-term response of the kidney to acute nephron loss under active nephrogenesis.

【 授权许可】

CC BY   
© Springer Nature Switzerland AG 2023

【 图 表 】

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