Exosomes Cause Preterm Birth in Mice: Evidence for Paracrine Signaling in Pregnancy
Exosomes Cause Preterm Birth in Mice: Evidence for Paracrine Signaling in Pregnancy
复制标题
DOI：
10.1038/s41598-018-37002-x
复制
发表时间：
2019-01-24
影响因子：
4.6
通讯作者：
Menon, Ramkumar
中科院分区：
文献类型：
--
作者：
Sheller-Miller, Samantha;Trivedi, Jayshil;Menon, Ramkumar
内分泌因素和胎儿器官成熟的信号被报道为出生时机的决定因素。为了检验外泌体的旁分泌信号传导是分娩的关键调节剂的假设，在整个妊娠期间分离并表征来自CD-1小鼠的母体血浆外泌体，并确定与差异表达的货物蛋白相关的生物学途径。结果表明，外泌体的形状和大小在整个妊娠期间保持不变;然而，从妊娠第5天（E）至E19天，观察到携带炎症介质的外泌体数量逐渐增加。此外，测定了源自胎儿-母体子宫组织的妊娠晚期（E18）血浆外泌体对分娩的影响。将E18外泌体腹膜内注射到E15小鼠中，定位于母体生殖道组织和子宫内胎儿隔室中。与足月分娩的对照组相比，外泌体处理的小鼠在E18时发生早产，并且在E17时子宫颈、子宫和胎膜中的炎症介质增加，但胎盘中没有。在注射早期妊娠（E9）外泌体的小鼠中未观察到这种效应。这项研究提供的证据表明，外泌体作为旁分泌介质的劳动和交付。
Endocrine factors and signals of fetal organ maturation are reported determinants of birth timing. To test the hypothesis that paracrine signaling by exosomes are key regulators of parturition, maternal plasma exosomes from CD-1 mice were isolated and characterized throughout gestation and the biological pathways associated with differentially-expressed cargo proteins were determined. Results indicate that the shape and size of exosomes remained constant throughout gestation; however, a progressive increase in the quantity of exosomes carrying inflammatory mediators was observed from gestation day (E)5 to E19. In addition, the effects of late-gestation (E18) plasma exosomes derived from feto-maternal uterine tissues on parturition was determined. Intraperitoneal injection of E18 exosomes into E15 mice localized in maternal reproductive tract tissues and in intrauterine fetal compartments. Compared to controls that delivered at term, preterm birth occurred in exosome-treated mice on E18 and was preceded by increased inflammatory mediators on E17 in the cervix, uterus, and fetal membranes but not in the placenta. This effect was not observed in mice injected with early-gestation (E9) exosomes. This study provides evidence that exosomes function as paracrine mediators of labor and delivery.