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Mechanisms of fertilization elucidated by gene-manipulated animals.

Okabe M - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: These phenomena were found more than 60 years ago.However, fundamental questions regarding the nature of capacitation and the timing of the acrosome reaction remain unsolved.Factors were postulated over time, but as their roles were not verified by gene-disruption experiments, widely accepted notions concerning the mechanism of fertilization are facing modifications.

View Article: PubMed Central - PubMed

Affiliation: Center for Genetic Analysis for Biological Responses, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka 565 0871, Japan.

ABSTRACT
Capacitation and the acrosome reaction are key phenomena in mammalian fertilization. These phenomena were found more than 60 years ago. However, fundamental questions regarding the nature of capacitation and the timing of the acrosome reaction remain unsolved. Factors were postulated over time, but as their roles were not verified by gene-disruption experiments, widely accepted notions concerning the mechanism of fertilization are facing modifications. Today, although in vitro fertilization systems remain our central research tool, the importance of in vivo observations must be revisited. Here, primarily focusing on our own research, I summarize how in vivo observations using gene-manipulated animals have elucidated new concepts in the mechanisms of fertilization.

No MeSH data available.


Related in: MedlinePlus

The mechanisms of fertilization, elucidated by gene-manipulated animals. (a) Spermatozoa that present Adam3 (or some unknown factor(s)) can migrate into the oviduct and reach the vicinity of the eggs. Acrosome reaction is induced before spermatozoa reach the zona pellucida and the fusion-related sperm protein Izumo1 on the outer acrosomal membrane migrates out to sperm surface (indicated by red color). (b) Spermatozoa bind to zona pellucida when mixed with cumulus-free oocytes.74 However, this binding (mostly observed between the acrosome-intact spermatozoa and zona pellucida) was dispensable. The spermatozoa that lost the so-called “zona-binding” ability remained able to fertilize eggs in vivo once the oviduct migration step was bypassed.293133 Moreover, the timing of the acrosome reaction is flexible, as acrosome-reacted spermatozoa recovered from the perivitelline space could penetrate the zona pellucida a second time and fertilize eggs.43 The mechanism of sperm penetration of zona pellucida is largely unknown. (c) Only acrosome-reacted spermatozoa can fuse with eggs. Spermatozoa without Izumo1 never fused with eggs.39Cd9 on the egg played an important role in fertilization,404142 but Cd9-disrupted females were not completely infertile. In addition, no direct interaction between Cd9 and Izumo1 was observed. This led us to predict a real counterpart for Izumo1. Using the newly established AVEXIS assay, JUNO was recently found to be a counterpart for Izumo1 on the egg.51 Modified from review.75
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Figure 1: The mechanisms of fertilization, elucidated by gene-manipulated animals. (a) Spermatozoa that present Adam3 (or some unknown factor(s)) can migrate into the oviduct and reach the vicinity of the eggs. Acrosome reaction is induced before spermatozoa reach the zona pellucida and the fusion-related sperm protein Izumo1 on the outer acrosomal membrane migrates out to sperm surface (indicated by red color). (b) Spermatozoa bind to zona pellucida when mixed with cumulus-free oocytes.74 However, this binding (mostly observed between the acrosome-intact spermatozoa and zona pellucida) was dispensable. The spermatozoa that lost the so-called “zona-binding” ability remained able to fertilize eggs in vivo once the oviduct migration step was bypassed.293133 Moreover, the timing of the acrosome reaction is flexible, as acrosome-reacted spermatozoa recovered from the perivitelline space could penetrate the zona pellucida a second time and fertilize eggs.43 The mechanism of sperm penetration of zona pellucida is largely unknown. (c) Only acrosome-reacted spermatozoa can fuse with eggs. Spermatozoa without Izumo1 never fused with eggs.39Cd9 on the egg played an important role in fertilization,404142 but Cd9-disrupted females were not completely infertile. In addition, no direct interaction between Cd9 and Izumo1 was observed. This led us to predict a real counterpart for Izumo1. Using the newly established AVEXIS assay, JUNO was recently found to be a counterpart for Izumo1 on the egg.51 Modified from review.75

Mentions: In any case, the timing of the acrosome reaction is flexible, as indicated long ago in the rabbits.46 These findings also indicated that the significant “sperm-zona binding” must occur between acrosome-reacted spermatozoa and the zona pellucida, while most of the classical “sperm-zona binding” assays were observing binding between acrosome-intact spermatozoa and the zona pellucida47 (Figure 1).


Mechanisms of fertilization elucidated by gene-manipulated animals.

Okabe M - Asian J. Androl. (2015 Jul-Aug)

The mechanisms of fertilization, elucidated by gene-manipulated animals. (a) Spermatozoa that present Adam3 (or some unknown factor(s)) can migrate into the oviduct and reach the vicinity of the eggs. Acrosome reaction is induced before spermatozoa reach the zona pellucida and the fusion-related sperm protein Izumo1 on the outer acrosomal membrane migrates out to sperm surface (indicated by red color). (b) Spermatozoa bind to zona pellucida when mixed with cumulus-free oocytes.74 However, this binding (mostly observed between the acrosome-intact spermatozoa and zona pellucida) was dispensable. The spermatozoa that lost the so-called “zona-binding” ability remained able to fertilize eggs in vivo once the oviduct migration step was bypassed.293133 Moreover, the timing of the acrosome reaction is flexible, as acrosome-reacted spermatozoa recovered from the perivitelline space could penetrate the zona pellucida a second time and fertilize eggs.43 The mechanism of sperm penetration of zona pellucida is largely unknown. (c) Only acrosome-reacted spermatozoa can fuse with eggs. Spermatozoa without Izumo1 never fused with eggs.39Cd9 on the egg played an important role in fertilization,404142 but Cd9-disrupted females were not completely infertile. In addition, no direct interaction between Cd9 and Izumo1 was observed. This led us to predict a real counterpart for Izumo1. Using the newly established AVEXIS assay, JUNO was recently found to be a counterpart for Izumo1 on the egg.51 Modified from review.75
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492058&req=5

Figure 1: The mechanisms of fertilization, elucidated by gene-manipulated animals. (a) Spermatozoa that present Adam3 (or some unknown factor(s)) can migrate into the oviduct and reach the vicinity of the eggs. Acrosome reaction is induced before spermatozoa reach the zona pellucida and the fusion-related sperm protein Izumo1 on the outer acrosomal membrane migrates out to sperm surface (indicated by red color). (b) Spermatozoa bind to zona pellucida when mixed with cumulus-free oocytes.74 However, this binding (mostly observed between the acrosome-intact spermatozoa and zona pellucida) was dispensable. The spermatozoa that lost the so-called “zona-binding” ability remained able to fertilize eggs in vivo once the oviduct migration step was bypassed.293133 Moreover, the timing of the acrosome reaction is flexible, as acrosome-reacted spermatozoa recovered from the perivitelline space could penetrate the zona pellucida a second time and fertilize eggs.43 The mechanism of sperm penetration of zona pellucida is largely unknown. (c) Only acrosome-reacted spermatozoa can fuse with eggs. Spermatozoa without Izumo1 never fused with eggs.39Cd9 on the egg played an important role in fertilization,404142 but Cd9-disrupted females were not completely infertile. In addition, no direct interaction between Cd9 and Izumo1 was observed. This led us to predict a real counterpart for Izumo1. Using the newly established AVEXIS assay, JUNO was recently found to be a counterpart for Izumo1 on the egg.51 Modified from review.75
Mentions: In any case, the timing of the acrosome reaction is flexible, as indicated long ago in the rabbits.46 These findings also indicated that the significant “sperm-zona binding” must occur between acrosome-reacted spermatozoa and the zona pellucida, while most of the classical “sperm-zona binding” assays were observing binding between acrosome-intact spermatozoa and the zona pellucida47 (Figure 1).

Bottom Line: These phenomena were found more than 60 years ago.However, fundamental questions regarding the nature of capacitation and the timing of the acrosome reaction remain unsolved.Factors were postulated over time, but as their roles were not verified by gene-disruption experiments, widely accepted notions concerning the mechanism of fertilization are facing modifications.

View Article: PubMed Central - PubMed

Affiliation: Center for Genetic Analysis for Biological Responses, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita, Osaka 565 0871, Japan.

ABSTRACT
Capacitation and the acrosome reaction are key phenomena in mammalian fertilization. These phenomena were found more than 60 years ago. However, fundamental questions regarding the nature of capacitation and the timing of the acrosome reaction remain unsolved. Factors were postulated over time, but as their roles were not verified by gene-disruption experiments, widely accepted notions concerning the mechanism of fertilization are facing modifications. Today, although in vitro fertilization systems remain our central research tool, the importance of in vivo observations must be revisited. Here, primarily focusing on our own research, I summarize how in vivo observations using gene-manipulated animals have elucidated new concepts in the mechanisms of fertilization.

No MeSH data available.


Related in: MedlinePlus