Mechanism of Fertilization: A Modern View

Okabe, Masaru

doi:10.1538/expanim.14-0026

Cited by 27 publications

(26 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many KO mice are fertile even though the targeted genes were thought essential for fertilization, based on in vitro experiments [e.g., Acr, Zp3r, Zan, B4galt1, Adam1b, and others. (6)]. Alternatively, without a preceding functional assay in vitro, many testis-enriched genes proved to be essential, by KO, for male reproduction.…”

Section: Significancementioning

confidence: 99%

Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

Miyata

Castaneda

Fujihara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

127

View full text Add to dashboard Cite

Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others.

show abstract

Section: Significancementioning

confidence: 99%

Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

Miyata

Castaneda

Fujihara

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

127

View full text Add to dashboard Cite

show abstract

“…1). There have been reviews on the roles of other molecules in fertilization including those involved in sperm-egg fusion, or in the changes in the cytoskeleton or the meiotic spindle (Jones 2007, Horner & Wolfner 2008, Clift & Schuh 2013, Okabe 2014. There are also reviews on aspects of Ca 2+ i homeostasis during oocyte maturation in preparation for fertilization (Machaca 2007, Wakai & Fissore 2013.…”

Section: Introductionmentioning

confidence: 99%

Molecular triggers of egg activation at fertilization in mammals

Sanders

Swann

2016

Reproduction

View full text Add to dashboard Cite

show abstract

“…This unique, tightly regulated, irreversible, single but complex exocytotic process releases the acrosomal contents which include Ca 2+ and enzymes, modifies membrane components, and exposes the inner acrosomal membrane to the extracellular medium (Dan 1952;Yanagimachi 1994). Sperm-egg coat penetration, fusion with the eggs' plasma membrane, and finally fertilization require the release and exposure of cell components resulting from this exocytotic process (Buffone et al 2014;Okabe 2014;Vacquier et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…4 and Mayorga et al 2007;Castillo Bennett et al 2010). However, in contrast to neurotransmitter release which occurs within milliseconds, acrosomal exocytosis takes many minutes (Buffone et al 2014;Okabe 2014;Vacquier et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Recent years have witnessed intense research and lively debate regarding the molecular identity of the physiological AR inductor(s), when, where, and how this reaction takes place, and the signaling cascades required for its outcome (Jin et al 2011;Buffone et al 2014;Nishigaki et al 2014;Okabe 2014). This issue deals with many of the questions mentioned above.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of Ion Channels in the Sperm Acrosome Reaction

Beltrán

Treviño

Mata-Martínez

et al. 2016

Sperm Acrosome Biogenesis and Function During Fertilization

View full text Add to dashboard Cite

The acrosome reaction (AR) is a unique exocytotic process where the acrosome, a single membrane-delimited specialized organelle, overlying the nucleus in the sperm head of many species, fuses with the overlying plasma membrane. This reaction, triggered by physiological inducers from the female gamete, its vicinity, or other stimuli, discharges the acrosomal content modifying the plasma membrane, incorporating the inner acrosomal membrane, and exposing it to the extracellular medium. The AR is essential for sperm-egg coat penetration, fusion with the eggs' plasma membrane, and fertilization. As in most exocytotic processes Ca(2+) is crucial for the AR, as well as intracellular pH and membrane potential changes. Thus, among the required processes needed for this reaction, ion permeability changes involving channels are pivotal. In spite of the key role ion channels play in the AR, their identity and regulation is not fully understood. Though molecular and pharmacological evidence indicates that various ionic channels participate during the AR, such as store-operated Ca(2+) channels and voltage-dependent Ca(2+) channels, whole cell patch clamp recordings have failed to detect some of them until now. Since sperm display a very high resistance and a minute cytoplasmic volume, very few channels are needed to achieve large membrane potential and concentration changes. Functional detection of few channels in the morphologically complex and tiny sperm poses technical problems, especially when their conductance is very small, as in the case of SOCs. Single channel recordings and novel fluorescence microscopy strategies will help to define the participation of ionic channels in the intertwined signaling network that orchestrates the AR.

show abstract

Mechanism of Fertilization: A Modern View

Cited by 27 publications

References 59 publications

Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

Molecular triggers of egg activation at fertilization in mammals

Role of Ion Channels in the Sperm Acrosome Reaction

Contact Info

Product

Resources

About