Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

Abstract

The distribution of the tyrosine kinase receptor c-Kit and its ligand stem cell factor (SCF) was evaluated by immunohistochemistry in primordial germ cells (PGCs) and human embryonic gonads during weeks 5–8 of prenatal life, and fetal ovaries during weeks 9–36 of prenatal life. Distinct c-Kit and SCF staining was present in primordial germ cells in the wall of the hindgut and in the dorsal mesentery, particularly on level with the 10th thoracic columnar segment. Several PGCs were in close contact with c-Kit-negative but SCF-positive autonomic nerve fibers of the dorsal mesentery. Many fibroblasts and mesothelial cells of the dorsal mesentery were clearly stained for SCF, but not for c-Kit. Prominent c-Kit and SCF staining was present in germ cells of the embryonic gonadal anlage and in oogonia during further ovarian development. However, oocytes were either unstained or faintly stained for SCF. Oocytes not yet enclosed in follicles or present in primordial follicles were either unstained or exhibited faint cytoplasmic c-Kit staining, whereas oocytes of growing preantral follicles again showed distinct cell membrane staining which decreased during further follicular growth. Theca cells did not stain for c-Kit. Some pregranulosa cells and the first formed granulosa cells of primordial follicles were c-Kit stained. Granulosa cells of other follicles were not c-Kit stained. In the inner part of the cortex, SCF immunolabeling was detected in some pregranulosa cells surrounding cords containing germ cells and involved in formation of primordial follicles. Granulosa cells of primordial and growing follicles, including medium-sized antral follicles also revealed SCF staining. In conclusion, this first report on SCF in human PGCs and embryonic and fetal ovaries together with the c-Kit data lend substantial countenance to the notion that c-Kit and SCF play important roles during ascent of primordial germ cells towards the gonadal anlage, and during oogenesis and folliculogenesis in the human fetal ovary. We suggest that both autocrine and paracrine mechanisms are involved in the proposed anti-apoptotic effect of the c-Kit/SCF duet while PGCs are present in the dorsal mesentery. The SCF-positive autonomic nerve fibers of the dorsal mesentery, mesothelial cells and fibroblasts may nurse and perhaps guide PGCs during their ascent.