Differentiation markers of Sertoli cells and germ cells in fetal and early postnatal human testis

Abstract

The definition of the temporal sequence of appearance of fetal markers during prenatal and early postnatal development in Sertoli and germ cells may be important for understanding the mechanisms underlying their reexpression in disorders of the adult testis. For this reason, we studied the expression of Sertoli and germ cell markers in 25 human testes spanning a period from 8 gestational weeks to 4 years. Well-characterized antibodies were employed to anti-Müllerian hormone (AMH), cytokeratin 18 (CK18), vimentin (VIM), M2A-antigen (M2A), germ cell alkaline phosphatase (GCAP), and somatic angiotensin-converting enzyme (sACE) on formalin-fixed and microwave-pretreated paraffin sections. In Sertoli cells, AMH and VIM were consistently present. While VIM and CK18 were coexpressed in embryonic testes, CK18 was progressively downregulated and completely absent from the 20th gestational week. M2A was absent or moderately expressed in fetal Sertoli cells but increased during further development. In germ cells, M2A was consistently found in primordial germ cells (PGCs) as well as in M- and T1-prespermatogonia. In contrast, sACE and GCAP were absent from PGCs but were a distinct feature of late M- and early T1-prespermatogonia and appeared predominantly between the 18th and the 22nd gestational weeks. Both T2-prespermatogonia and postnatal prespermatogonia were devoid of any marker. While CK18 represents a differentiation marker for fetal Sertoli cells, M2A, GCAP, and sACE can be used as differentiation markers for the discrimination of different germ cell types during human prespermatogenesis. Because various immunophenotypes reflect distinct differentiation stages, this knowledge may be important for understanding adult testicular pathology.

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

“…By contrast, in human and marmoset, a survey of available data on gene expression profiles, cell behaviors (e.g. proliferation or migration), and cell positioning within seminiferous cords (central vs basal location) clearly shows large overlaps of gonocyte and spermatogonial subpopulations for a period spreading from late gestation to early infancy (Sharpe et al 2003, Franke et al 2004, Gaskell et al 2004, Pauls et al 2006, Jørgensen et al 2012, Ewen et al 2013, McKinnell et al 2013, O'Shaughnessy & Fowler 2014.…”

Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis

“…In addition, the IFs are able to modulate cellular responses to metabolic stress, programmed cell death, cell migration, and even tissue growth (Coulombe & Wong 2004). Vimentin is an IF protein often expressed transiently during development (Menet et al 2001) that has been described in Sertoli cells during fetal and postnatal periods (Romeo et al 1995, Show et al 2003, Franke et al 2004, where it plays important roles in the modifications of Sertoli cell morphology, junctional processes, structural integrity, and cytoplasmic organization that occur during spermatogenesis (Russell & Peterson 1985, Tanemura et al 1994, Show et al 2003, He et al 2007.…”

The role of the gubernaculum in the descent and undescent of the testis

“…Evidence now supports the notion that type-A spermatogonia, which appear between 3 and 12 months of age, are the putative stem cells for postpubertal spermatogenesis [Franke et al 2004;Maclaughlin and Donahoe, 2004]. Importantly, transformation of gonocytes at 3-6 months of age is impaired in cryptorchidism, which is the likely cause of subsequent infertility, because of a deficient stem cell pool [Kolon et al 2004].…”