Development, function and fate of fetal Leydig cells

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Article (peer-reviewed)

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During fetal testis development, fetal Leydig cells (FLCs) are found to be originated from multiple progenitor cells. FLC specification and function are under tight regulation of specific genes and signaling proteins. Furthermore, Sertoli cells play a crucial role to regulate FLC differentiation during fetal testis development. FLC progenitor- and FLC-produced biomolecules are also involved in the differentiation and activity of rodent FLCs. The main function of FLCs is to produce androgens to masculinize male embryos. However, FLCs are capable of producing androstenedione but not testosterone due to the lack of 17β-HSD (17β-hydroxysteroid dehydrogenase), but fetal Sertoli cells express 17β-HSD which thus transforms androstenedione to testosterone. On the other hand, FLCs produce activin A to regulate Sertoli cell proliferation, and Sertoli cells in turn modulate testis cord expansion. It is now generally accepted that adult Leydig cells (ALCs) replace FLCs during postnatal development gradually to produce testosterone to support spermatogenesis as FLCs undergo degeneration after birth in neonatal and pre-pubertal mouse testes. However, based on studies using genetic tracing mouse models, FLCs are found to persist in adult testes, making up ∼20% of total Leydig cells. In this review, we evaluate the latest findings regarding the development, function and fate of FLCs during testis development.