The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon’s head to tail

Abstract

Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid-specific factors in controlling fertility. Although a male contraceptive ‘pill' is still many years away, research into the production of new small-molecule contraceptives targeting spermatid-specific proteins is the right avenue.

Transcriptome‐wide changes in testes reveal molecular differences in photoperiod‐induced seasonal reproductive life‐history states in migratory songbirds

“…The overlap of RNA‐Seq and qPCR assay results validated LHS‐dependent testicular gene expressions in buntings. In LD states, we found an increased HOOK1 expression, consistent with its role in spermatid differentiation (Chen et al, ), and a decreased RGS2 expression, consistent with its downregulation with the transition from spermatogonia to spermatocyte stage in murine spermatogenesis (Lalancette, Platts, Lu, Lu, & Krawetz, ). We also found high CYFIP2 mRNA expression in both LDES and LDLS, although the levels were still significantly lower in former than the latter state.…”

Impact of a mild scrotal heating on sperm chromosomal abnormality, acrosin activity and seminal alpha-glucosidase in human fertile males

“…The mechanism of heat‐induced semen parameter alterations and loss of germ cell DNA integrity have been demonstrated (Banks et al., ; Durairajanayagam et al., ; Liu, ; Liu et al., ; Paul, Melton, et al., ; Paul, Murray, et al., ; Paul et al., ; Rao et al., , ). The acrosome is derived from the Golgi apparatus, covers the anterior part of the sperm nucleus and plays an essential role in mammalian fertilisation (Chen, Batool, et al., ; Chen, Chen, et al., ). Sperm capacitation requires hyperactivated sperm motility, invasive integral DNA and acrosome reaction (AR).…”

Sperm quality parameters are increased and asymmetric in house mouse hybrids

“…The sperm head and tail are bridged by the myosin-based connecting piece. A comprehensive search detected various factors that interact with myosin subunits (Chen et al 2016). The Oaz3 gene that encodes ornithine decarboxylase antizyme 3 [located on chromosome 3], the Odf1 gene encoding the outer dense fibre of sperm tails 1 [chromosome 15: 38.2 Mb] and the Spata6 encoding spermatogenesis associated 6 [chromosome 4] participate in myosin-based microfilament formation (genomic positions were retrieved at http://www.informatics.jax.org/).…”

“…Lower fertility in males due to abnormal spermatozoa has been reported in many animals including humans, but its pathogenic causes, including genetic factors, remain largely unknown (Chen et al 2016). Data from knockout mice suggest that numerous genes can impair spermiogenesis (reviewed in Chen et al 2016).…”

“…Lower fertility in males due to abnormal spermatozoa has been reported in many animals including humans, but its pathogenic causes, including genetic factors, remain largely unknown (Chen et al 2016). Data from knockout mice suggest that numerous genes can impair spermiogenesis (reviewed in Chen et al 2016). In nature, the incidence of genetically induced abnormalities can be affected due to hybridization between diverged populations in zones of secondary contact (Alund et al 2013).…”