Does fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials? A study of FA1 in embryonic, fetal, and placental tissue and in maternal circulation

Abstract

Fetal antigen 1 (FA1) is a circulating EGF multidomain glycoprotein. FA1 and its membrane-associated precursor is defined by the mRNAs referred to as delta-like (dlk), preadipocyte factor 1 (pref-1) or zona glomerulosa-specific factor (ZOG). Using a polyclonal antibody recognising both forms, the localisation of FA1/dlk was analysed in embryonic and fetal tissues between week 5 to 25 of gestation and related to germinal origin and development. FA1 was observed in endodermally derived hepatocytes, glandular cells of the pancreas anlage, and in respiratory epithelial cells. FA1 was also present in mesodermally derived cells of the renal proximal tubules, adrenal cortex, Leydig and Hilus cells of the testes and ovaries, fetal chondroblasts, and skeletal myotubes. Ectodermally derived neuro- and adenohypophysial cells, cells in the floor of the 3rd ventricle and plexus choroideus were also FA1 positive. The number of cells expressing FA1 decreased during fetal development where the expression became restricted to specific functional cells. Epidermis, gut epithelium, gall bladder, blood cells, spleen, thyroid gland, salivary glands, and smooth muscle cells were FA1 negative. Analysis of extra-embryonic tissues from normal and pathological pregnancies revealed FA1 in stromal cells surrounding the blood islands of the yolk sac as well as in placental fibroblasts where the expression was most pronounced in diploid, androgenic complete hydatidiform moles. However, as measured by ELISA, the circulating maternal FA1 levels in complete moles were not different from normal pregnancies. The results presented suggest that FA1 is a growth and/or differentiation factor extensively expressed in immature cells and down-regulated during fetal development. FA1 down-regulation was associated with a shift in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions.