The secondary human yolk sac has an immunophenotype indicative of both hepatic and intestinal differentiation

Although the microscopy of the secondary human yolk sac (SHYS) is well known, few studies have addressed its immunohistochemical profile. The SHYS is involved in the synthesis, absorption and transfer of various proteins and behaves as a temporary liver and intestine. The objective of this study was to evaluate the presence of immunohistochemical markers of hepatic and intestinal function in the SHYS. We performed a retrospective histological and immunohistochemical study of 26 SHYS from spontaneous abortions and tubal pregnancies, 15 of which were from the 7th to 8th week. The antibodies used were against alpha-foetoprotein (AFP), glypican 3 (GLP3), hepatocyte-paraffin-1 (HepPar-1), villin, CDX2, SALL4 and podoplanin (D2-40). Early SHYS from the 5th to the 8th week revealed a network of intracellular vesicles communicating with the lumen of endodermal tubules that were highlighted by intense membrane AFP expression. Endodermal cells consistently expressed AFP, GLP3, SALL4, hep-par-1, villin and CDX2, while mesothelial cells only expressed D2-40. The endodermal layer of the SHYS from the 5th to the 8th week revealed a transient canalicular network which was highlighted by strong membranous AFP expression; this may represent the substrate of a SHYS transport system during its period of maximal activity. The synthetic and transfer functions of the yolk sac endoderm were reflected in a hybrid immunophenotype in which proteins characteristic of hepatic function such as AFP, GLP3, SALL4 and hep-par-1 were coexpressed simultaneously with others such as villin and CDX2, indicative of an intestinal role.