Reduced amounts and abnormal forms of phospholipase C zeta (PLC) 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.
Source: Human Reproduction, Volume 24, Number 10, 24 October 2009 , pp. 2417-2428(12)
Publisher: Oxford University Press
Abstract:BACKGROUNDIn mammals, oocyte activation at fertilization is thought to be induced by the sperm-specific phospholipase C zeta (PLC). However, it still remains to be conclusively shown that PLC 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 PLC.METHODS AND RESULTSImmunofluorescence studies showed PLC 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 PLC in sperm from infertile men, and in some cases, the presence of an abnormally low molecular weight form of PLC. In one non-globozoospermic case, DNA analysis identified a point mutation in the PLC 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 PLC protein. cRNA corresponding to mutant PLC 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.CONCLUSIONSOur findings illustrate the importance of PLC during fertilization and suggest that mutant forms of PLC may underlie certain types of human male infertility.
Document Type: Research article
Publication date: 2009-10-24
- Human Reproduction features full-length, peer-reviewed papers reporting original research, clinical case histories, as well as opinions and debates on topical issues. Papers published cover the scientific and medical aspects of reproductive physiology and pathology, endocrinology, andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues. The highest scientific and editorial standard is maintained throughout the journal along with a rapid rate of publication.
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- In this Subject: Anatomy & Physiology , Obstetrics & Gynecology
- By this author: 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.