Fetal and Adult Leydig Cells Are of Common Orig

Abstract

In the developing testis, fetal Leydig cells appear in mice at embryonic day 12.5, in rats at embryonic day 14.5, and in human at weeks 7–8 of pregnancy (Huhtaniemi and Pelliniemi 1992; Pelliniemi et al. 1996; Majdic et al. 1998; Yao and Barsoum 2007). The fetal Leydig cells form clusters that are surrounded by a basal lamina that becomes discontinuous after birth (Kuopio and Pelliniemi 1989; Kuopio et al. 1989a). According to O’Shaugnessy et al. (2006) and Yao and Barsoum (2007), the first visible Leydig cells could be recognized by staining for 3β-hydroxysteroid dehydrogenase or cytochrome P450 side chain cleavage enzyme (CytP450scc) at 12.5 days post coitus (dpc). This occurs after the formation of the testicular cords and the coelomic vessel. At this time, it is not clear whether the first Leydig cells transdifferentiate directly from their stem/progenitors within the gonadal mesenchyme or via stem/progenitor Leydig cells (pericytes) in the testicular vasculature. After initial differentiation and proliferation of fetal Leydig cells around day 12 of gestation (Gondos 1980), the fetal Leydig cell population remains virtually unchanged in mice, and, for example, the number of Leydig cells is stable between day 16 of gestation and day 5 after birth (Baker and O’Shaughnessy 2001a). This suggests that the fetal Leydig cells are terminally differentiated and do not divide (Zhang et al. 2008). However, there are also reports indicating that the number of fetal Leydig cells increases between embryonic days 17 and 21 or immediately before birth (Kerr et al. 1988). The latter would not be compatible with the idea that fetal Leydig cells arise by transdifferentiation from stem/progenitor Leydig cells in analogy with the adult Leydig cell population. After birth, the number of fetal Leydig cells significantly decreases. In contrast, Kerr and Knell (1988) proposed that 50–75% of the original “fetal-type” Leydig cell population present at birth persists in the adult testis. In this context, observations (Davidoff et al. 2004) that “fetal-type” Leydig cells are generated during postnatal development are significant, since these cells could be hardly distinguished from the prenatal fetal Leydig cells.