Proliferation and Apoptosis in Aged and Photoregressed Mammalian Seminiferous Epithelium, with Particular Attention to Rodents and Humans

Abstract

Imbalances in the proliferation and apoptosis processes are involved in numerous epithelial alterations. In the seminiferous epithelium, normal spermatogenesis is regulated by spermatogonia proliferation and germ cell apoptosis, and both processes are involved in diverse pathological alterations of the seminiferous epithelium. Other physiological phenomena including aging and short photoperiod, in which apoptosis and proliferation seem to play important roles, cause testicular changes. Aging is accompanied by diminished proliferation and increased apoptosis, the latter occurring in specific states of the seminiferous cycle and considered the cause of epithelium involution. However, there is no clear evidence concerning whether proliferation decreases in the spermatogonia themselves or is due to an alteration in the cell microenvironment that surrounds them. As regards the factors that regulate the process, the data are scant, but it is considered that the diminution of c-kit expression in the spermatagonia, together with the diminution in antiapoptotic factors (Bcl-x(L))) of the intrinsic molecular pathway of apoptosis play a part in epithelial regression. A short photoperiod, especially in rodents, produces a gradual involution of the seminiferous epithelium, which is related with increased apoptosis during the regression phase and a diminution of apoptosis during recrudescence. Proliferative activity varies, especially during the total regression phase, when it usually increases in the undifferentiated spermatogonia. In other species showing seasonal reproduction, however, decreased proliferation is considered the main factor in the regression of the seminiferous epithelium. Little is known about how both phenomena are regulated, although data in rodents suggest that both the intrinsic and extrinsic pathways of apoptosis contribute to the increase in this process. In conclusion, regression of the seminiferous epithelium in physiological situations, as in many pathological situations, is a result of alterations in equilibrium between the proliferation and apoptosis of germinal cell types. However, both physiological phenomena showed important differences as regard proliferation/apoptosis and their regulation pathways, probably as a result of their irreversible or reversible character.

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

“…Although in both species this phenomenon is well-known, the Roe Deer has been considered as a species where germ cell apoptosis is not the main mechanism responsible for epithelial atrophy, whereas in Brown Hare apoptosis plays a critical role in such atrophy. In the case of the Syrian hamster, the relationship between apoptosis-proliferation shows a similar behavior to that observed in the Brown Hare in the state of complete regression (Pastor et al, 2011). The detailed study of apoptosis/proliferation ratio in this work allows us to better understand what mechanisms are responsible for testicular atrophy during testicular regression in Syrian hamsters.…”

“…Among such pathological conditions are toxic exposure (Wine et al, 1997;Boekelheide, 2005), growth factor depletion, hormonal alterations associated with gonadotropin and/or androgen deprivation (Woolveridge et al, 1999;Bakalska et al, 2004), treatment with estradiol (Blanco-Rodr ıguez & Mart ınez-Garc ıa, 1997; Chaki et al, 2006), heat exposure (Yin et al, 1997;Paul et al, 2009), cryptorchidism (Ohta et al, 1996;Mizuno et al, 2009), radiation (Meistrich, 1993;Liu et al, 2007), chemotherapeutic treatment (Cai et al, 1997), and vascular ischemia (Turner et al, 1997(Turner et al, , 2004. Among normal physiological conditions, testicular regression owing to photoperiod (a reversible process) and aging (irreversible process) can be included (Pastor et al, 2011). In both cases an imbalance between the phenomena of proliferation and cell death results in depletion of the seminiferous epithelium.…”

Effects of aging on the male reproductive system

“…In contrast to spermatogonia, apoptotic rate of primary spermatocytes, as shown by TUNEL positivity, was significantly elevated compared to controls, which might, in part, explain the mechanism of germ cell loss in aged men [92]. The discrepancy might be due to an age-related deterioration of spermatogonial stem cell niche accompanied by a compensatory decrease in apoptotic spermatogonia [91]. In supporting evidence, a recent histological and ultrastructural study has shown increased apoptosis along with a reduced proliferation in germ cells of the aging testes [93].…”

“…Furthermore, high oxidative stress leads to increased apoptosis and spermatozoal DNA damage [79]. Although apoptosis is essential for spermatogenesis under normal conditions, the balance between proliferation of spermatogonia and apoptosis of different germ cell types appears to be disturbed with aging [91]. In spermatogonia of aged men, both expression of Ki-67, a marker of cell proliferation activity, and apoptotic rate were found to be decreased compared to young controls [92].…”

Identification of Apoptotic Cells by Means of Lectin Histochemistry: State of the Art Review

“…Consequently, the cell cycle includes both the cell proliferation cycle and programmed cell death (apoptosis) [1,2].…”