Caspase signalling pathways in human spermatogenesis

Abstract

Purpose Little is known about the apoptotic mechanisms involved in abnormal spermatogenesis. In order to describe the significance of apoptosis in azoospermia, testicular tissue from abnormal spermatogenesis was analysed. Methods Testicular treatment biopsies were obtained from 27 men. Five presented oligozoospermia, 9 obstructive azoospermia (4 congenital bilateral absence of the vas deferens; 5 secondary azoospermia) and 13 nonobstructive azoospermia (5 hypospermatogenis; 3 maturation arrest; 5 Sertoli-cell-only syndrome). Immunohistochemical staining was performed for active caspases-3, −8 and −9. The presence of active caspases in Sertoli cells and germ cells was analyzed using stereological tools. Results Increased active caspase-3 was found in Sertoli-cellonly syndrome. No significant differences were found in maturation arrest. In hypospermatogenesis, primary spermatocytes were the germ cells with higher active caspases. Oligozoospermia and secondary obstruction showed significant differences among germ cells for the presence of all active caspases. In oligozoospermia, spermatogonia presented significant increased active caspase-9 in relation to active caspase-8. In primary obstruction and hypospermatogenesis, germ cells presented significant increased active caspases-3 and −9. Conclusions Results suggest that increased active caspase-3 might be involved in Sertoli-cell-only syndrome etiology. In cases of hypospermatogenesis, intrinsic lesions at the meiotic stage seem to be related to the pathology. In secondary obstruction apoptosis is suggested to be initiated due to extrinsic and intrinsic lesions, whereas in primary obstruction only the intrinsic apoptotic pathway seems to be present. Finally, in oligozoospermic patients spermatogonia death by mitochondrial damage additionally to meiosis malfunctioning, might be on the origin of the decreased sperm output.

Mitochondria functionality and sperm quality

“…Although the capacity of mature sperm to carry out apoptosis has been questioned due to the paucity of cytoplasm, it is well known that human sperm can possess apoptotic markers and that this may influence sperm function and perhaps be involved in the removal of DNA-damaged sperm in the female reproductive tract , or, alternatively, result from leftover apoptotic phenomena in the testis, possibly related to cases of male infertility (Almeida et al 2013). It is worth mentioning that some studies note increases in sperm DNA damage as evidence for apoptosis, but, while DNA damage is certainly one of the main consequences of apoptosis, apoptosis may not be the only possible mechanism involved , Aitken & De Iuliis 2010, Sakkas & Alvarez 2010, and the notion of DNA damage directly linked to a canonical apoptosis cascade in sperm has been questioned .…”

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

“…Accordingly, altered expression patterns of a panoply of apoptosis-related genes have been described in human testes with defective spermatogenesis. The association of death receptors and the extrinsic pathway of apoptosis with male infertility have been suggested by several studies, which showed enhanced expression of FasL in cases of maturation arrest and Sertoli cell-only syndrome, the later characterised by the absence of germ cell in the seminiferous epithelium ( Refs 5,34,35,36,37,38). Cavalcanti et al found an increased expression of tumour necrosis factor alpha (TNF-α) family member 10 (also known as TNF-α-related apoptosis inducing ligand, TRAIL) in the testes of subfertile men comparatively with potentially fertile (Ref.…”

Apoptotic and nonapoptotic function of caspase 7 in spermatogenesis

“…Recent studies report that caspase signal pathways are relative to the apoptosis of germ cells 1617. However, whether the function of caspase 7 is involved in spermatogenesis remains unknown.…”