Formation and function of the manchette and flagellum during spermatogenesis

Lehti, Mari S.; Sironen, Anu

doi:10.1530/rep-15-0310

Cited by 214 publications

(193 citation statements)

References 78 publications

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“…We assume it should be present in the locations related to sperm flagella formation, such as the manchette, a structure proposed to transporting cargo proteins for flagella formation (Kierszenbaum and Tres, 2004; Lehti and Sironen, 2016); the basal bodies, the template for flagella formation (Marshall, 2008); and the developing flagella in the elongating spermatids. Thus, other specific antibodies should be generated to target IFT27 in male germ cells.…”

Section: Discussionmentioning

confidence: 99%

Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice

Zhang

Liu

et al. 2017

Developmental Biology

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Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27:Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survive to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymis contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the “9+2” axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the conditional Ift25 knockout mice, appeared to be normal in the conditional Ift27 knockout mice. Our findings suggest that like IFT25, IFT27, even though not required to ciliogenesis in somatic cells, is essential for sperm flagella formation, sperm function, and male fertility in mice. IFT25 and IFT27 control sperm formation/function through many common mechanisms, but IFT25 has additional roles beyond IFT27.

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Section: Discussionmentioning

confidence: 99%

Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice

Zhang

Liu

et al. 2017

Developmental Biology

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“…MEIG1 is localized in the whole cell body of spermatocytes, and is recruited to the manchette by PACRG in elongating/condensing spermatids. The manchette is a structure present only in elongating/condensing spermatids, and its major proposed function is to transport cargo proteins to build sperm flagella (Kierszenbaum, 2002; Lehti and Sironen, 2016). It appears that the roles of the MEIG1/PACRG complex and IFT proteins overlap in the transport of cargo during the assembly of cilia and flagella.…”

Section: Discussionmentioning

confidence: 99%

Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice

Zhang

et al. 2016

MBoC

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“…53 The basic platform of the manchette consists of microtubules, actin filaments and the associated motor protein (e.g., myosin). 54 Next, we introduced the several manchette-specific protein complexes and the consequences of their disruption in spermatid elongation (Figure 2). …”

Section: Manchette Of Elongating Spermatidsmentioning

confidence: 99%

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

et al. 2016

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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.

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Formation and function of the manchette and flagellum during spermatogenesis

Cited by 214 publications

References 78 publications

Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice

Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice

Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice

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

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