Shi Ruijing, Zhao Lianbi, Cai Wenbin, Wei Mengying, Zhou Xueying, Yang Guodong, Yuan Lijun
Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):602-608. doi: 10.1016/j.bbrc.2016.12.097. Epub 2016 Dec 18.
Maternal diabetes mellitus induces an increased risk of congenital heart defects (CHD), however, the exact mechanisms are still not fully illustrated. In this study, diabetic pregnant C57BL/6 mice were induced by injection of streptozotocin before mating. Compared with the control normal mice, diabetic pregnant mice displayed significant changes of the exosomal miRNA contents in the blood, as revealed by RNA-seq analysis. Multiple of these miRNAs were found involved in cardiac development regulation. Moreover, fluorescence labeled exosomes and gold nanoparticles could cross the placenta barrier and infiltrated into the embryonic organs/tissues, including the heart, during embryonic development. Injection of diabetic maternal exosomes strikingly increased the risk of CHD in the normal recipient pregnant mice. Taken together, we could draw the conclusion that maternal exosomes in diabetes could cross the maternal-fetal barrier and contribute to the cardiac development deficiency possibly via miRNAs, providing new insights in CHD prevention and treatment.
母体糖尿病会增加先天性心脏病(CHD)的风险,然而,确切机制仍未完全阐明。在本研究中,在交配前通过注射链脲佐菌素诱导糖尿病妊娠C57BL/6小鼠。RNA测序分析显示,与对照正常小鼠相比,糖尿病妊娠小鼠血液中外泌体miRNA含量发生了显著变化。发现其中多个miRNA参与心脏发育调控。此外,荧光标记的外泌体和金纳米颗粒可穿过胎盘屏障,并在胚胎发育过程中渗入包括心脏在内的胚胎器官/组织。注射糖尿病母体来源的外泌体显著增加了正常受体妊娠小鼠患CHD的风险。综上所述,我们可以得出结论,糖尿病母体的外泌体可穿过母胎屏障,并可能通过miRNA导致心脏发育缺陷,这为CHD的预防和治疗提供了新的见解。