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- Title
Reduced amounts and abnormal forms of phospholipase C zeta (PLCzeta) in spermatozoa from infertile men.
- Authors
Heytens, E.; Parrington, J.; Coward, K.; Young, C.; Lambrecht, S.; Yoon, S.-Y.; Fissore, R. A.; Hamer, R.; Deane, C. M.; Ruas, M.; Grasa, P.; Soleimani, R.; Cuvelier, C. A.; Gerris, J.; Dhont, M.; Deforce, D.; Leybaert, L.; De Sutter, P.
- Abstract
<bold>Background: </bold>In mammals, oocyte activation at fertilization is thought to be induced by the sperm-specific phospholipase C zeta (PLCzeta). However, it still remains to be conclusively shown that PLCzeta is the endogenous agent of oocyte activation. Some types of human infertility appear to be caused by failure of the sperm to activate and this may be due to specific defects in PLCzeta.<bold>Methods and Results: </bold>Immunofluorescence studies showed PLCzeta to be localized in the equatorial region of sperm from fertile men, but sperm deficient in oocyte activation exhibited no specific signal in this same region. Immunoblot analysis revealed reduced amounts of PLCzeta in sperm from infertile men, and in some cases, the presence of an abnormally low molecular weight form of PLCzeta. In one non-globozoospermic case, DNA analysis identified a point mutation in the PLCzeta gene that leads to a significant amino acid change in the catalytic region of the protein. Structural modelling suggested that this defect may have important effects upon the structure and function of the PLCzeta protein. cRNA corresponding to mutant PLCzeta failed to induce calcium oscillations when microinjected into mouse oocytes. Injection of infertile human sperm into mouse oocytes failed to activate the oocyte or trigger calcium oscillations. Injection of such infertile sperm followed by two calcium pulses, induced by assisted oocyte activation, activated the oocytes without inducing the typical pattern of calcium oscillations.<bold>Conclusions: </bold>Our findings illustrate the importance of PLCzeta during fertilization and suggest that mutant forms of PLCzeta may underlie certain types of human male infertility.
- Subjects
PHOSPHOLIPASE C; CONCEPTION; OVUM; SPERMATOZOA; MALE infertility; CALCIUM metabolism; AMINO acids; ANIMAL experimentation; BINDING sites; COMPARATIVE studies; ESTERASES; IMMUNOBLOTTING; INFERTILITY; MATHEMATICAL models; RESEARCH methodology; MEDICAL cooperation; MICE; GENETIC mutation; PROTEINS; RESEARCH; THEORY; EVALUATION research
- Publication
Human Reproduction, 2009, Vol 24, Issue 10, p2417
- ISSN
0268-1161
- Publication type
journal article
- DOI
10.1093/humrep/dep207