Role of prosaposin in the mouse embryogenesis

丙皂苷(PSAP)是神经鞘脂溶酶体水解所需的皂苷(SAP)的前体蛋白。虽然已知PSAP本身可以分泌到几种体液中，但其生理功能尚不清楚。PSAP缺陷小鼠(PSAP-/-)出生的频率要低得多，提示PSAP在小鼠胚胎发育过程中起着重要作用。在这项研究中，我们研究了PSAP在野生型小鼠胚胎中的时空表达以及PSAP-/-胚胎的表型。小鼠胚胎组织中PSAP的蛋白水平在胚胎第6.5天较低，在胚胎7.5~9.5天开始升高。免疫组织化学分析显示PSAP在E7.5~9.5的蜕膜和E10.5的胎盘海绵状滋养层高表达。SAPS在卵黄囊内脏内胚层的大溶酶体中高表达。PSAP-/-胚胎的组织病理学检查表明，早在e7.5左右就出现了发育异常。蜕膜内可见细胞皱缩。卵黄囊内脏内胚层中的大溶酶体数量减少，大小减少。这些PSAP-/-胚胎的致死表型被母体过表达的PSAP挽救。我们的发现表明，PSAP和SAP在小鼠妊娠早期的蜕膜、卵黄囊和胎盘部位起着重要的作用。

Prosaposin (PSAP) is the precursor protein of saposins (SAPs) which are required for the lysosomal hydrolysis of sphingolipids. Although PSAP itselfis known to be secreted into several body fluids, its physiological function is not well understood. PSAP deficient mice (Psap-/-) are born at the much lower frequency suggesting the function of PSAP during the mouse embryogenesis. In this study, we investigated the temporal and spatial expression of PSAP in the wild-type mouse embryo and the phenotype of Psap-/-embryo. Protein levels of PSAP in the mouse embryonic tissues were low at embryonic day (E) 6.5 and increased at E7.5 to 9.5. Immunohistochemical analyses showed high expressions of PSAP in decidua at E7.5 to 9.5 and in spongiotrophoblastic layer of placenta at E10.5. SAPs were highly expressed in the large lysosomes of visceral endoderm of yolk sac. Histopathological examination of Psap-/-embryos indicated the developmental abnormality as early as at around E7.5. Shrunken cells were observed in decidua. The number and the size of large lysosome in visceral endoderm of yolk sac were decreased. These lethal phenotypes of Psap-/-embryos were rescued by maternal overexpression of PSAP. Our findings suggest that PSAP and SAPs play important roles during the early stage of mouse pregnancy, at the site of decidua, yolk sac and placenta.