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Reduced amounts and abnormal forms of phospholipase C zeta (PLC zeta) in spermatozoa from infertile men

Elke Heytens UGent, J Parrington, K Coward, C Young, STEFANIE LAMBRECHT UGent, SY Yoon, RA Fissore, R. Hamer, CM Deane and M Ruas, et al. (2009) HUMAN REPRODUCTION. 24(10). p.2417-2428
abstract
In mammals, oocyte activation at fertilization is thought to be induced by the sperm-specific phospholipase C zeta (PLC zeta). However, it still remains to be conclusively shown that PLC zeta 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 zeta. Immunofluorescence studies showed PLC zeta 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 zeta in sperm from infertile men, and in some cases, the presence of an abnormally low molecular weight form of PLC zeta. In one non-globozoospermic case, DNA analysis identified a point mutation in the PLC zeta 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 zeta protein. cRNA corresponding to mutant PLC zeta 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. Our findings illustrate the importance of PLC zeta during fertilization and suggest that mutant forms of PLC zeta may underlie certain types of human male infertility.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
FERTILIZATION FAILURE, EMBRYO DEVELOPMENT, CA2+ OSCILLATIONS, MOUSE OOCYTES, CALCIUM IONOPHORE, INTRACYTOPLASMIC SPERM INJECTION, ROUND-HEADED SPERM, ASSISTED OOCYTE ACTIVATION, OSCILLATION-INDUCING ACTIVITY, MAMMALIAN FERTILIZATION
journal title
HUMAN REPRODUCTION
Hum. Reprod.
volume
24
issue
10
pages
12 pages
publisher
Oxford University Press
place of publication
OXFORD
Web of Science type
Article
Web of Science id
000269952600006
JCR category
OBSTETRICS & GYNECOLOGY
JCR impact factor
3.859 (2009)
JCR rank
4/70 (2009)
JCR quartile
1 (2009)
ISSN
0268-1161
DOI
10.1093/humrep/dep207
language
English
UGent publication?
yes
classification
A1
id
784718
handle
http://hdl.handle.net/1854/LU-784718
date created
2009-11-19 11:29:59
date last changed
2010-03-26 14:19:02
@article{784718,
  abstract     = {In mammals, oocyte activation at fertilization is thought to be induced by the sperm-specific phospholipase C zeta (PLC zeta). However, it still remains to be conclusively shown that PLC zeta 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 zeta.
Immunofluorescence studies showed PLC zeta 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 zeta in sperm from infertile men, and in some cases, the presence of an abnormally low molecular weight form of PLC zeta. In one non-globozoospermic case, DNA analysis identified a point mutation in the PLC zeta 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 zeta protein. cRNA corresponding to mutant PLC zeta 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.

Our findings illustrate the importance of PLC zeta during fertilization and suggest that mutant forms of PLC zeta may underlie certain types of human male infertility.},
  author       = {Heytens, Elke and Parrington, J and Coward, K and Young, C and LAMBRECHT, STEFANIE and Yoon, SY and Fissore, RA and Hamer, R. and Deane, CM and Ruas, M and Grasa, P and Soleimani, Reza and Cuvelier, Claude and Gerris, Jan and DHONT, MARC and Deforce, Dieter and Leybaert, Luc and De Sutter, Petra},
  issn         = {0268-1161},
  journal      = {HUMAN REPRODUCTION},
  keyword      = {FERTILIZATION FAILURE,EMBRYO DEVELOPMENT,CA2+ OSCILLATIONS,MOUSE OOCYTES,CALCIUM IONOPHORE,INTRACYTOPLASMIC SPERM INJECTION,ROUND-HEADED SPERM,ASSISTED OOCYTE ACTIVATION,OSCILLATION-INDUCING ACTIVITY,MAMMALIAN FERTILIZATION},
  language     = {eng},
  number       = {10},
  pages        = {2417--2428},
  publisher    = {Oxford University Press},
  title        = {Reduced amounts and abnormal forms of phospholipase C zeta (PLC zeta) in spermatozoa from infertile men},
  url          = {http://dx.doi.org/10.1093/humrep/dep207},
  volume       = {24},
  year         = {2009},
}

Chicago
Heytens, Elke, J Parrington, K Coward, C Young, STEFANIE LAMBRECHT, SY Yoon, RA Fissore, et al. 2009. “Reduced Amounts and Abnormal Forms of Phospholipase C Zeta (PLC Zeta) in Spermatozoa from Infertile Men.” Human Reproduction 24 (10): 2417–2428.
APA
Heytens, E., Parrington, J., Coward, K., Young, C., LAMBRECHT, S., Yoon, S., Fissore, R., et al. (2009). Reduced amounts and abnormal forms of phospholipase C zeta (PLC zeta) in spermatozoa from infertile men. HUMAN REPRODUCTION, 24(10), 2417–2428.
Vancouver
1.
Heytens E, Parrington J, Coward K, Young C, LAMBRECHT S, Yoon S, et al. Reduced amounts and abnormal forms of phospholipase C zeta (PLC zeta) in spermatozoa from infertile men. HUMAN REPRODUCTION. OXFORD: Oxford University Press; 2009;24(10):2417–28.
MLA
Heytens, Elke, J Parrington, K Coward, et al. “Reduced Amounts and Abnormal Forms of Phospholipase C Zeta (PLC Zeta) in Spermatozoa from Infertile Men.” HUMAN REPRODUCTION 24.10 (2009): 2417–2428. Print.