Phosphoglycerate Kinase 2 (PGK2) Is Essential for Sperm Function and Male Fertility in Mice1
Autor: | G. Barrie Kitto, William D. Willis, Polina V. Danshina, Deborah A. O'Brien, Qunsheng Dai, Edward M. Eddy, Christopher B. Geyer, Eugenia H. Goulding, John R. McCarrey |
---|---|
Rok vydání: | 2010 |
Předmět: |
Male
Isozyme Mice Adenosine Triphosphate Testis Animals Spermatogenesis Phosphoglycerate kinase 1 education reproductive and urinary physiology Sperm motility Glyceraldehyde 3-phosphate dehydrogenase Mice Knockout education.field_of_study Phosphoglycerate kinase Sperm Count biology urogenital system Glyceraldehyde-3-Phosphate Dehydrogenases Cell Biology General Medicine Spermatozoa Sperm Acid Anhydride Hydrolases Cell biology Isoenzymes Mice Inbred C57BL Phosphoglycerate Kinase Fertility Reproductive Medicine Biochemistry Sperm Motility biology.protein Homologous recombination Research Article |
Zdroj: | Biology of Reproduction. 82:136-145 |
ISSN: | 1529-7268 0006-3363 |
DOI: | 10.1095/biolreprod.109.079699 |
Popis: | Phosphoglycerate kinase 2 (PGK2), an isozyme that catalyzes the first ATP-generating step in the glycolytic pathway, is encoded by an autosomal retrogene that is expressed only during spermatogenesis. It replaces the ubiquitously expressed phosphoglycerate kinase 1 (PGK1) isozyme following repression of Pgk1 transcription by meiotic sex chromosome inactivation during meiotic prophase and by postmeiotic sex chromatin during spermiogenesis. The targeted disruption of Pgk2 by homologous recombination eliminates PGK activity in sperm and severely impairs male fertility, but does not block spermatogenesis. Mating behavior, reproductive organ weights (testis, excurrent ducts, and seminal vesicles), testis histology, sperm counts, and sperm ultrastructure were indistinguishable between Pgk2(-/-) and wild-type mice. However, sperm motility and ATP levels were markedly reduced in males lacking PGK2. These defects in sperm function were slightly less severe than observed in males lacking glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS), the isozyme that catalyzes the step preceding PGK2 in the sperm glycolytic pathway. Unlike Gapdhs(-/-) males, the Pgk2(-/-) males also sired occasional pups. Alternative pathways that bypass the PGK step of glycolysis exist. We determined that one of these bypass enzymes, acylphosphatase, is active in mouse sperm, perhaps contributing to phenotypic differences between mice lacking GAPDHS or PGK2. This study determined that PGK2 is not required for the completion of spermatogenesis, but is essential for sperm motility and male fertility. In addition to confirming the importance of the glycolytic pathway for sperm function, distinctive phenotypic characteristics of Pgk2(-/-) mice may provide further insights into the regulation of sperm metabolism. |
Databáze: | OpenAIRE |
Externí odkaz: |