Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque

Abstract

Experimental cryptorchidism is a common model for examining the expression and function of heat-sensitive spermatogenesis-related genes in testis. Previous studies have shown that germ cells in cryptorchid testis die mainly in an apoptotic way. The molecular mechanism, however, is still unclear. We have established unilateral cryptorchid monkey model (Cynomolgus Macaque) to identify possible molecules involved in the germ cell apoptosis. The degree of germ cell apoptosis, the morphology of the cryptorchid testis, and the changes in the serum concentration of FSH, LH and testosterone after cryptorchid surgery were analyzed. Sertoli cell marker molecule vimentin, the orphan receptor LRH-1, as well as the mitochondria-related protein HSP60 and Bcl-2 were examined. Our results showed that the weight of the cryptorchid testis decreased in a time-dependent manner started from day 7 after the surgery, while the weight of the scrotal testis had no obvious change. HE staining showed that from day 5, some germ cells were detached from the epithelium. A massive degeneration of the seminiferous epithelium characteristic of epithelial structural disorganization and the formation of multinucleated giant cells as well as vacuoles was observed on day 10 and 15. The cryptorchidism induced a marked germ cell apoptosis on day 3 after the operation, reaching a peak level on day 7.

Effects of chronic heat stress on the expressions of heat shock proteins 60, 70, 90, A2, and HSC70 in the rabbit testis

“…That is in agreement with previous observations in the testis of cryptorchid monkeys (Tao et al 2006) and in rat skeletal muscles after heat stress (Oishi et al 2002). In the present study, the expression level of HSP60 after the 9-week recovery period was still higher than that of the control.…”

Expression of Nitric Oxide Synthase During Germ Cell Apoptosis in Testis of Cynomolgus Monkey After Testosterone and Heat Treatment

“…We previously demonstrated that heat‐induced germ cell apoptosis mainly occurred in spermatocytes and round spermatids, whereas spermatogonia were not sensitive to H in nonhuman primates (Zhou et al, 2002; Zhang et al, 2003a,b, 2005; Tao et al, 2006). Exogenous T was also capable of inducing germ cell apoptosis in monkeys (Zhou et al, 2001b; Lue et al, 2006).…”

“…These mice also confer partial resistance to heat‐induced germ cell apoptosis. Furthermore, germ cell apoptosis was dramatically increased in a time‐dependent manner after 43°C local treatment of monkey testes (Zhang et al, 2005) or experimental cryptorchidism (Tao et al, 2006). The number of apoptotic cells reached the maximum at day 8 and returned to the normal control level at the end of the recovery phase after 43°C warming (Zhang et al, 2005); this observation was consistent with the profile of changes in iNOS observed in the present study.…”

“…The number of apoptotic cells reached the maximum at day 8 and returned to the normal control level at the end of the recovery phase after 43°C warming (Zhang et al, 2005); this observation was consistent with the profile of changes in iNOS observed in the present study. We have also carried out experiments to examine a possible mechanism of heat‐induced germ cell apoptosis by looking at expression of some apoptotic marker molecules such as Fas/FasL, Bcl‐2/Bax, p53, or heat stress—related molecules (eg, Hsf and Hsps) in testes after H or T (Guo et al, 2000; Mu et al, 2000; Zhou et al, 2001a,b, 2002; Zhang et al, 2003a,b; Tao et al, 2006). The number of apoptotic germ cells increased on day 3, reaching a maximum on day 15 after experimental cryptorchidism (Tao et al, 2006).…”

Metastasis tumor antigen 1 is involved in the resistance to heat stress‐induced testicular apoptosis

“…Previous work has shown that the germ-cell loss associated with cryptorchidism in mammalian occurs by apoptosis, but the resultant mechanism has not been elucidated [2]. Interestingly, the balance between germ-cell proliferation and apoptosis in adults is also critical to control spermatogenesis [3].…”