Abstract：
Gestational diabetes mellitus (GDM) presents a substantial population health concern. Previous studies have revealed that GDM can ultimately influence nephron endowment. In this study, we established a GDM mouse model to investigate the embryological alterations and molecular mechanisms underlying the development of congenital anomalies of the kidney and urinary tract (CAKUT) affected by GDM. Our study highlights that GDM could contribute to the manifestation of CAKUT, with prevalent phenotypes characterized by isolated hydronephrosis and duplex kidney complicated with hydronephrosis in mice. Ectopic ureteric buds (UBs) and extended length of common nephric ducts (CNDs) were noted in the metanephric development stage. The expression of Ret and downstream p-ERK activity were enhanced in UBs, which indicated the alteration of RET/MAPK/ERK pathway may be one of the mechanisms contributing to the increased occurrence of CAKUT associated with GDM.
摘要：
妊娠期糖尿病（GDM）是一个重要的人群健康问题。先前的研究表明，GDM可以最终影响肾单位禀赋。在这项研究中,我们建立了GDM小鼠模型，以研究受GDM影响的先天性肾脏和泌尿道异常（CAKUT）发生的胚胎学改变和分子机制。我们的研究强调，GDM可能有助于CAKUT的表现，在小鼠中具有以孤立性肾积水和双重肾并发肾积水为特征的普遍表型。在后肾发育阶段注意到异位输尿管芽（UB）和共同肾管（CND）的延长长度。UB中Ret的表达和下游p-ERK活性增强,这表明RET/MAPK/ERK通路的改变可能是导致GDM相关CAKUT发生增加的机制之一。
