Role of prosaposin in the mouse embryogenesis

鞘脂激活蛋白原（PSAP）是鞘脂激活蛋白（SAP）的前体蛋白，其是鞘脂的溶酶体水解所必需的。虽然已知PSAP本身可分泌到多种体液中，但其生理功能尚不清楚。PSAP缺陷型小鼠（Psap-/-）的出生频率低得多，表明PSAP在小鼠胚胎发育过程中的功能。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和Psap-/-胚胎的表型。小鼠胚胎组织中PSAP的蛋白水平在胚胎日（E）6.5时较低，并在E7.5至9.5时增加。免疫组化分析显示PSAP在E7.5至9.5的蜕膜和E10.5的胎盘海绵滋养层中高表达。SAP在卵黄囊内脏内胚层的大溶酶体中高度表达。Psap-/-胚胎的组织学检查表明早在E7.5左右就出现发育异常。蜕膜细胞皱缩。卵黄囊脏内胚层大溶酶体数量减少，体积缩小。PSAP-/-胚胎的这些致死表型被PSAP的母体过表达所拯救。我们的研究结果表明，PSAP和SAP在小鼠妊娠早期，在蜕膜，卵黄囊和胎盘的位置发挥重要作用。

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.