Male germ cell apoptosis: regulation and biology

Abstract

Cellular apoptosis appears to be a constant feature in the adult testis and during early development. This is essential because mammalian spermatogenesis is a complex process that requires precise homeostasis of different cell types. This review discusses the latest information available on male germ cell apoptosis induced by hormones, toxins and temperature in the context of the type of apoptotic pathway either the intrinsic or the extrinsic that may be used under a variety of stimuli. The review also discusses the importance of mechanisms pertaining to cellular apoptosis during testicular development, which is independent of exogenous stimuli. Since instances of germ cell carcinoma have increased over the past few decades, the current status of research on apoptotic pathways in teratocarcinoma cells is included. One other important aspect that is covered in this review is microRNA-mediated control of germ cell apoptosis, a field of research that is going to see intense activity in near future. Since knockout models of various kinds have been used to study many aspects of germ cell development, a comprehensive summary of literature on knockout mice used in reproduction studies is also provided.

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…A high level of spermatogonial apoptosis is physiological at this time point, since e.g. correct Sertoli/germ cell‐ratio for the successive rounds of spermatogenesis is established during the first wave of spermatogenesis (Shaha et al ., 2010). Important effectors of the first‐wave apoptosis are the pro‐apoptotic Bax and anti‐apoptotic Bcl‐w, Bcl‐X L and Bcl‐2 (Knudson et al ., 1995; Furuchi et al ., 1996; Rodriguez et al ., 1997; Yan et al ., 2003; Jahnukainen et al ., 2004).…”

Relationship between apoptotic markers in semen from fertile men and demographic, hormonal and seminal characteristics

“…1,2 Fas/FasL provides another pathway for germ cell apoptosis. 3 Apoptotic pathways converge at the level of caspases, which are considered to be the key enzymes of apoptosis, acting both as initiators and executers of programmed cell death, 1,3 but caspase independent pathways have also been described. 4 The finely-tuned apoptotic mechanisms eliminate abnormal cells, and thereby minimize the negative consequences of abnormal spermatozoa on male fertility and on the health of offspring.…”

“…It has been proposed that sperm DNA damage can originate from oxidative stress, from unligated strand breaks physiologically formed during spermatogenesis to help the process of chromatin remodelling, and from defective or 'abortive' apoptotic processes [8][9][10] initiated post meiotically when cells are no longer able to complete the classical pathways of programmed cell death. 1, 3,11 Notably, it has been stressed that these mechanisms are not mutually exclusive and, in reality, DNA damage may arise from combinations of all three mechanisms. 5 The theoretical framework of abortive apoptosis is based on the assumption that as germ cells progress into their terminal differentiation pathway, they become more and more transcriptionally and translationally silent and progressively lose their capacity to undergo programmed cell death in the form of classical apoptosis.…”

Paternal contribution to development: Sperm genetic damage and repair in fish

“…The former are consequence of failures in the recombination process during meiosis, in the cell renewal by apoptosis induction during spermatogenesis (Shaha et al 2010) or during chromatin remodeling at spermiogenesis (Hendrich and Bickmore 2001;Li et al 2014;Rathke et al 2014). Moreover, membranes from immature spermatozoa are very susceptible to suffer lipid peroxidation, whose products are genotoxic and mutagenic and can affect to the mature ones (Aitken et al 2014).…”