Role of prosaposin in the mouse embryogenesis

丙皂苷（PSAP）是鞘脂溶酶体水解所需的皂苷前体蛋白。虽然已知PSAP本身可分泌到几种体液中，但其生理功能尚不清楚。PSAP缺陷小鼠（PSAP -/-）的出生频率要低得多，这表明PSAP在小鼠胚胎发生过程中发挥了作用。在本研究中，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蛋白水平在胚胎日(E) 6.5时较低，在E7.5 ~ 9.5时升高。免疫组化分析显示PSAP在E7.5 ~ 9.5时在蜕膜中高表达，在E10.5时在胎盘海绵状滋养层中高表达。SAPs在卵黄囊内脏内胚层的大溶酶体中高度表达。Psap-/-胚胎的组织病理学检查早在E7.5左右就显示发育异常。蜕膜内细胞萎缩。卵黄囊内脏内胚层大溶酶体数量减少，大小减小。Psap-/-胚胎的这些致死性表型通过母体过表达Psap得以挽救。我们的研究结果表明，PSAP和SAPs在小鼠妊娠早期蜕膜、卵黄囊和胎盘部位发挥重要作用。

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.