The presence of abnormal spermatozoa in the ejaculate: Did apoptosis fail?

Abstract

With the successful use of Assisted Reproduction, in particular intracytoplasmic sperm injection (ICSI), to treat infertile couples we have become less discriminating with the quality of spermatozoa we use to treat our patients. Numerous studies have shown the presence of nuclear DNA strand breaks in human ejaculated spermatozoa. The reason why human spermatozoa, in particular from men with abnormal semen parameters, possess these abnormalities in their nuclear DNA is still not clear. Two processes that have been linked to the presence of nuclear DNA strand breaks in spermatozoa are anomalies in apoptosis during spermatogenesis or problems in the packaging of the chromatin during spermiogenesis. Understanding the mechanisms responsible for producing abnormal spermatozoa in the human will improve our knowledge about certain causes of male infertility. More importantly, the impact of such sperm, if selected to perform ICSI, needs to be better understood so that any detrimental paternal effects can be avoided.

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

“…One of the hypothesized triggers of testis apoptosis is the impairment of sperm chromatin maturation (60). This idea is supported by the association between apoptotic markers and cell immaturity (24,46).…”

Pathogenic Consequences in Semen Quality of an Autoimmune Response against the Prostate Gland: From Animal Models to Human Disease

“…Numerous studies have now shown the presence of nuclear DNA strand breaks and apoptosis in human ejaculated spermatozoa from infertile patients and the abnormal persistence of apoptotic marker proteins (32). Why human spermatozoa possess these abnormalities is still not clear (33).…”

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

“…Several theories have been put forward to explain the existence of these abnormal cells, [5][6][7] present also in otherwise normal ejaculates as assessed by the World Health Organisation's (WHO) guidelines for conventional semen analysis (WHO, 1999). 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.…”