002. Sertoli cell terminal differentiation: doing a ‘U’ turn on a one way street

Abstract

The concept of terminal differentiation of Sertoli cells has been challenged and this new information has important implications for male fertility. The mammalian Sertoli cell has two distinct functions: (i) formation of the seminiferous cords and (ii) provision of nutritional and structural support to the developing germ cells. For these to occur successfully, Sertoli cells must undergo numerous maturational changes between foetal and adult life, the main switches occur around the onset of puberty, coincident with the rise in serum gonadotrophins. These switches include the loss of proliferative activity and the formation of the blood testis barrier. Follicle stimulating hormone (FSH) plays a key role in supporting Sertoli cell proliferation in early postnatal life and thus is critical in establishing sperm output in adulthood. After puberty, the size of the Sertoli cell population is considered to be stable and unmodifiable by hormones. This accepted view has been contested as data shows that the size of the adult Sertoli cell population is modifiable by hormone suppression, and that Sertoli cells can regain proliferative activity when stimulated by FSH in the Djungarian hamster¹. The molecular mechanism(s) by which Sertoli cells re-enter proliferation are not known in this model however a study demonstrated that helix-loop-inhibitor of differentiation proteins can induce terminally differentiated Sertoli cells to re-enter the cell cycle and proliferate². Thyroid hormone and testosterone may be involved in the cessation of Sertoli cell proliferation. Gonadotrophin suppression in the adult Djungarian hamster also results in the disruption of the blood testis barrier and spatial organisation of the inter Sertoli cell tight junction proteins and as a consequence the loss of all germ cells that reside inside the blood testis barrier. FSH restores the organisation of these tight junction proteins, which is associated with the appearance of more mature germ cells. It is expected that the integrity of the blood testis barrier is also re-established. It is suggested that this demonstrated plasticity of the adult Sertoli cell may be relevant in clinical settings, particularly to some types of infertility and testicular malignancies where Sertoli cells have failed to undergo these important maturational switches.

   (1) Chaudhary et al. (2005) Biol. Reprod. 72, 1205.
   (2) Meachem et al. (2005) Biol. Reprod. 72, 1187.