Modelling human sperm-egg interactions in vitro: signal transduction pathways regulating the acrosome reaction

Benoff, Susan

doi:10.1093/molehr/4.5.453

Cited by 65 publications

(67 citation statements)

References 224 publications

(292 reference statements)

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“…The molecular mechanisms and the signal transduction pathways mediating the processes of acrosome reaction are partially defined: changes in protein phosphorylation and dephosphorylation of sperm proteins, including Ca 2C -dependent processes, seem to play a primary role in the second messenger regulatory mechanisms (for a review, see Benoff 1998, Breitbart & Naor 1999, Baldi et al 2000, Guraya 2000, Topfer-Petersen et al 2000, Urner & Sakkas 2003. There is evidence for the involvement of cAMP-dependent protein kinase (PKA) in the mammalian acrosome reaction: adenylate cyclase activity and cAMP generation increased during this process in human spermatozoa (De Jonge et al 1991); adenylate cyclase stimulators such as forskolin, and the cAMP analogue dibutyryl cAMP, induced the acrosome reaction in a dose-dependent manner in human and ram spermatozoa (Anderson et al 1992, Garde & Roldan 2000, Harrison & Meizel 2000; and PKA inhibitors have been reported to suppress human sperm acrosome reaction (Harrison & Meizel 2000).…”

Section: Discussionmentioning

confidence: 99%

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A

Ashizawa¹,

Wishart²,

Katayama³

et al. 2006

Reproduction

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The signal transduction pathways involved in the regulation of the acrosome reaction and motility of fowl spermatozoa were investigated. The motility and acrosomal integrity of fowl spermatozoa in TES/NaCl buffer, with or without homogenised inner perivitelline layers (IPVL), prepared from laid fowl eggs, was almost negligible at 40 8C. In the presence of 2 mmol CaCl 2 /l at 40 8C, motility became vigorous and the acrosome reaction was stimulated when IPVL was added. In the absence of Ca 2C , motility was stimulated by the addition of calyculin A and okadaic acid, both specific inhibitors of protein phosphatase-type 1 (PP1) and -type 2A (PP2A), but Okadaic acid, which is a weaker inhibitor of PP1, did not completely restore motility at 40 8C. However, the acrosome reaction was significantly and equally stimulated in a dose-dependent manner by both inhibitors in the range of 10-1000 nmol/l, when spermatozoa were incubated with IPVL but without Ca 2C . These inhibitors did not stimulate the acrosome reaction in the absence of IPVL. The vigorous motility of spermatozoa, stimulated by the addition of Ca 2C, was reduced gradually as the concentrations of SC-9, a selective activator of protein kinase C (PKC), were increased and a similar SC-9-induced inhibition was observed in the acrosome reaction in the presence of Ca 2C and IPVL. These results confirm that IPVL is necessary for the activation of the acrosome reaction in fowl spermatozoa and that Ca 2C plays an important role in the stimulation of motility and acrosomal exocytosis. Furthermore, it appears that the intracellular molecular mechanisms for the regulation of acrosome reaction of fowl spermatozoa are different from those for the restoration of motility, i.e., protein dephosporylation involving PP1 and/or PP2A in the former, and PP1 alone in the latter case. In addition, the activation of PKC may contribute to a decrease in the flagellar movement and acrosome reaction of fowl spermatozoa.

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Section: Discussionmentioning

confidence: 99%

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A

Ashizawa¹,

Wishart²,

Katayama³

et al. 2006

Reproduction

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“…PAF has been implicated in proper sperm motility (3,4) and acrosomal function (5). The major regulatory enzymes for PAF biosynthesis via the de novo pathway, including acetyltransferase and cholinephosphotransferase, are present in spermatozoa (6).…”

mentioning

confidence: 99%

Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis

Yan

Assadi

Wynshaw‐Boris

et al. 2003

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

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Platelet-activating factor (PAF) has been shown to affect sperm motility and acrosomal function, thereby altering fertility. PAF acetylhydrolase 1b (PAFAH1B) hydrolyzes PAF and is composed of three subunits [the lissencephaly (LIS1) protein and ␣1 and ␣2 subunits] and structurally resembles a GTP-hydrolyzing protein.Besides the brain, transcripts for Lis1, ␣1, and ␣2 are localized to meiotic and early haploid germ cells. Here, we report disruptions of the ␣2 (Pafah1b2) and ␣1 (Pafah1b3) genes in mice. Male mice homozygous null for ␣2 (␣2 ؊/؊ ) are infertile, and spermatogenesis is disrupted at mid-or late pachytene stages of meiosis or early spermiogenesis. Whereas mice homozygous mutant for ␣1 (␣1 ؊/؊ ) have normal fertility and normal spermatogenesis, those with disruptions of both ␣1 and ␣2 (␣1 ؊/؊ ␣2 ؊/؊ ) manifest an earlier disturbance of spermatogenesis with an onset at preleptotene or leptotene stages of meiosis. Testicular Lis1 protein levels are up-regulated in the ␣2 ؊/؊ and ␣1 ؊/؊ ␣2 ؊/؊ mice. Lowering Lis1 levels by inactivating one allele of Lis1 in ␣2 null or ␣1͞␣ 2 null genetic backgrounds (i.e., ␣2 ؊/؊ Lis1 ؉/؊ or ␣1 ؊/؊ ␣2 ؊/؊ Lis1 ؉/؊ mice) restored spermatogenesis and male fertility. Our data provide evidence for unique roles of the PAFAH1B complex and, particularly, the lissencephaly protein Lis1 in spermatogenesis.testis ͉ apoptosis ͉ lissencephaly

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“…PAF is a potent signaling phospholipid in various tissues (6,7), including the central nervous system (8 -12) and the reproductive organs (13,14). PAF has been implicated in sperm motility (15,16) and acrosomal function (17) but not in spermatogenesis. It has also been suggested that PAF plays a role in the pathogenesis of testicular ischemia (18).…”

mentioning

confidence: 99%

Inactivation of a Testis-specific Lis1 Transcript in Mice Prevents Spermatid Differentiation and Causes Male Infertility

Nayernia¹,

Vauti

Meinhardt

et al. 2003

Journal of Biological Chemistry

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Lis1 protein is the non-catalytic component of platelet-activating factor acetylhydrolase 1b (PAF-AH 1B) and associated with microtubular structures. Hemizygous mutations of the LIS1 gene cause type I lissencephaly, a brain abnormality with developmental defects of neuronal migration. Lis1 is also expressed in testis, but its function there has not been determined. We have generated a mouse mutant (LIS1 GT/GT ) by gene trap integration leading to selective disruption of a Lis1 splicing variant in testis. Homozygous mutant males are infertile with no other apparent phenotype. We demonstrate that Lis1 is predominantly expressed in spermatids, and spermiogenesis is blocked when Lis1 is absent. Mutant spermatids fail to form correct acrosomes and nuclei appear distorted in size and shape. The tissue architecture in mutant testis appears severely disturbed displaying collapsed seminiferous tubules, mislocated germ cells, and increased apoptosis. These results provide evidence for an essential and hitherto uncharacterized role of the Lis1 protein in spermatogenesis, particularly in the differentiation of spermatids into spermatozoa.

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Modelling human sperm-egg interactions in vitro: signal transduction pathways regulating the acrosome reaction

Cited by 65 publications

References 224 publications

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A

Regulation of acrosome reaction of fowl spermatozoa: evidence for the involvement of protein kinase C and protein phosphatase-type 1 and/or -type 2A

Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis

Inactivation of a Testis-specific Lis1 Transcript in Mice Prevents Spermatid Differentiation and Causes Male Infertility

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