Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

Okabe, Masaru; Cummins, James M.

doi:10.1007/s00018-007-7037-7

Cited by 30 publications

(23 citation statements)

References 101 publications

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“…As the past gene disruption research history indicates, it is very difficult to predict the role of certain factors in fertilization (Okabe and Cummins, 2007); however, defects of more than 100 genes are known to cause infertility (http://www.informatics.jax.org/searches/ Phat.cgi?id=MP:0001925#top). This indicates that the best way to elucidate the mechanism of fertilization is to accumulate information on genes that relate to infertility by gene disruption experiments.…”

Section: Discussionmentioning

confidence: 99%

Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse

Fujihara

Murakami

Inoue

et al. 2010

Journal of Cell Science

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SummaryMammalian fertilization is a multistep process that culminates in the fusion of the sperm and egg plasma membrane. It is widely accepted that the equatorial segment of the acrosome-reacted sperm is important in initiating fusion with the egg plasma membrane during fertilization. There are various proteins known to be distributed only in the equatorial segment of sperm. The role of these proteins must be clarified to understand the membrane fusion process. We produced a mouse line that lacked SPESP1 (sperm equatorial segment protein 1) and analyzed the fertilizing ability of the sperm. The average number of pups that were fathered by Spesp1 +/-and Spesp1 -/-males was significantly lower than that of wild-type fathers. In these mouse lines, fewer sperm were found to migrate into oviducts and fewer eggs were fertilized. The Spesp1 +/-and Spesp1 -/-sperm showed a lower fusing ability compared with the wildtype sperm. The disruption of Spesp1 was shown to cause an aberrant distribution of various sperm proteins. Moreover, scanning electron microscopy revealed that the membrane in the equatorial segment area, which usually forms an acrosomal sheath, disappears after acrosome reaction in Spesp1-deficient mice. It was demonstrated that SPESP1 is necessary to produce the fully 'fusion competent' sperm.

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Section: Discussionmentioning

confidence: 99%

Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse

Fujihara

Murakami

Inoue

et al. 2010

Journal of Cell Science

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“…This reveals that little was known then of the mechanisms involved in their fertilization, and that a number of the current assumptions were not correct. However, in the early postwar period a number of important observations appeared, not least because of the introduction of the phase contrast microscope and of methods for whole-mount studies of mammalian While the main thrust of research on mammalian fertilization now involves molecules that mediate gamete interaction, common models being targeted mutations in the mouse (Okabe and Cummins, 2007), these novel evolutionary features have dogged the mammalian field for years, and not to understand their adaptive significance and how they may relate brings at least the risk of wrong interpretations and time spent investigating blind alleys. Fortunately, the collective evidence now makes it possible to float some explanations.…”

Section: Introductionmentioning

confidence: 99%

Puzzles of mammalian fertilization and beyond

Bedford¹

2008

Int. J. Dev. Biol.

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A complexity imposed on the events of conception during the evolution of eutherian mammals is reflected not only in the placenta but also in a series of gamete-related novelties that involve the design of sperm and eggs, their interactions leading to fertilization, epididymal function, and even the scrotal state. While their functional significance has been difficult to determine, I suggest on the basis of present evidence that the genesis of these novel features relates ultimately to changes in the egg associated with nidation, that they imply a new fertilization strategy, and that most are causally linked -a major first 'domino' being the formidable zona pellucida. The eutherian zona pellucida stands out by virtue of an elastic resilience and thickness which allow it to stretch around the expanding blastocyst. However, this quality of the zona together with its relative protease-insensitivity creates a physical challenge which appears to have determined the design of the sperm head, its behaviour at fertilization, and indirectly even the pattern of sperm maturation in the epididymis. In turn, that pattern appears to have evoked the development of the sperm storage function of the cauda region, with both sperm capacitation and the scrotal state as ultimate legacies of this. Coincidentally, the vulnerability of the small yolkless egg to polyspermy appears to have selected for a unique parsimonious pattern of sperm transport in the Fallopian tube, and possibly for the role of the cumulus oophorus as a sperm sequestering device. These ideas are supported generally by evidence from marsupials, as well as by the deviant patterns seen in some insectivorous mammals.

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“…Crisp1 -/-mice were found to be fertile (Figure 2 A and B) (Da Ros et al, 2008), a result that adds to a growing number of reports of fertile mice lacking proteins proposed to be involved in the fertilization process (Okabe and Cummins, 2007). Based on the observation that many of these fertile "knock out" mice often exhibited other reproductive defi ciencies (Baba et al, 2002;Lu and Shur, 1997), Crisp1 -/-males were evaluated for evidence of changes in different parameters related to reproductive function.…”

Section: Crisp1mentioning

confidence: 83%

Cysteine-Rich Secretory Proteins (CRISP) and their role in mammalian fertilization

et al. 2011

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Epididymal protein CRISP1 is a member of the CRISP (Cysteine-RIch Secretory proteins) family and is involved in sperm-egg fusion through its interaction with complementary sites on the egg surface. Results from our laboratory have shown that this binding ability resides in a 12-amino-acid region corresponding to a highly conserved motif of the CRISP family, named Signature 2 (S2). In addition to this, our results revealed that CRISP1 could also be involved in the previous step of sperm binding to the zona pellucida, identifying a novel role for this protein in fertilization. As another approach to elucidate the participation of CRISP1 in fertilization, a mouse line containing a targeted disruption of CRISP1 was generated. Although CRISP1-defi cient mice exhibited normal fertility, CRISP1-deffi cient sperm presented a decreased level of protein tyrosine phosphorylation during capacitation, and an impaired ability to fertilize both zona-intact and zonafree eggs in vitro, confi rming the proposed roles for the protein in fertilization. Evidence obtained in our laboratory indicated that testicular CRISP2 would also be involved in sperm-egg fusion. Competition assays between CRISP1 and CRISP2, as well as the comparison of their corresponding S2 regions, suggest that both proteins bind to common complementary sites in the egg. Together, these results suggest a functional cooperation between CRISP1 and CRISP2 to ensure the success of fertilization.

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Mechanisms of sperm-egg interactions emerging from gene-manipulated animals

Cited by 30 publications

References 101 publications

Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse

Sperm equatorial segment protein 1, SPESP1, is required for fully fertile sperm in mouse

Puzzles of mammalian fertilization and beyond

Cysteine-Rich Secretory Proteins (CRISP) and their role in mammalian fertilization

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