Clinical 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. In 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. Based 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.

中文翻译：

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持续肾发生过程中新生儿肾单位丢失后长期肾纤维化的性别差异

临床研究表明，女性在肾脏疾病的发生和进展中发挥着保护作用。最近的实验研究表明，在雄性大鼠中，持续肾发生过程中的早期肾单位损失伴随着严重的长期后遗症。在人类中，肾单位的形成主要发生在妊娠晚期，在妊娠 36 周时停止。由于围产期并发症，在此脆弱时期出生的早产儿可能会出现急性肾单位损失。在大鼠中，肾发生持续到出生后第 10 天，反映了人类早产儿持续肾发生的情况。在我们的新生儿单肾切除动物模型中，雌性和雄性大鼠在出生第一天就进行了单肾切除。假设性别依赖性差异，1年后评估长期肾脏结果。无论男女，新生儿单肾切除术后 1 岁时均未出现动脉高血压。未切除肾的雌性和雄性动物中出现代偿性体重增加和剩余肾脏的肾小球肥大。间质炎症和纤维化的选定标志物受到性别依赖性的调节。新生儿单肾切除术后，女性中单核细胞趋化蛋白-1 的表达增加，而男性中 M1 巨噬细胞的肾小管间质浸润显着升高。与雌性大鼠相比，新生未进行肾切除的雄性大鼠有更多的肾小球硬化和足细胞损伤，这是通过半定量评分和结蛋白染色进行评估的。RT-PCR显示雌性大鼠新生期单肾切除后剩余对侧肾脏中肾脏发育和功能候选基因wt-1、nephrin、synaptopodin、gdnf和itga8的表达高于雄性。基于这些观察，我们得出结论，女性在肾脏对活跃肾发生下急性肾单位损失的长期反应中具有保护作用。