Phosphoglycerate Kinase 2 (PGK2) Is Essential for Sperm Function and Male Fertility in Mice
Polina V. Danshina,Christopher B. Geyer,Qunsheng Dai,Eugenia H. Goulding,William D. Willis,G. Barrie Kitto,John R. McCarrey,Edward M. Eddy,Deborah A. O'Brien +8 more
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TLDR
It is determined that PGK2 is not required for the completion of spermatogenesis, but is essential for sperm motility and male fertility, and alternative pathways that bypass the PGK step of glycolysis exist.Abstract:
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.read more
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References
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C. P. Leblond,Yves Clermont +1 more
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Meiotic sex chromosome inactivation
TL;DR: This work has established sex chromosome asynapsis as the primary trigger of MSCI, and it is now clear that it is maintained, although not completely, well beyond meiosis and into sperm development.
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Glyceraldehyde 3-phosphate dehydrogenase-s, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility
Kiyoshi Miki,Weidong Qu,Weidong Qu,Eugenia H. Goulding,William D. Willis,Donna O. Bunch,Lillian F. Strader,Sally D. Perreault,Edward M. Eddy,Deborah A. O'Brien +9 more
TL;DR: The critical role of glycolysis in sperm and its dependence on this sperm-specific enzyme suggest that GAPDS is a potential contraceptive target, and that mutations or environmental agents that disrupt its activity could lead to male infertility.
Journal ArticleDOI
Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility.
David J. Dix,James W. Allen,Barbara W. Collins,Chisato Mori,Noriko Nakamura,Patricia Poorman-Allen,Eugenia H. Goulding,Edward M. Eddy +7 more
TL;DR: Analysis of nuclei and genomic DNA indicated that the failure of meiosis in Hsp70-2 -/- mice was coincident with a dramatic increase in spermatocyte apoptosis, suggesting that HSP 70-2 participates in synaptonemal complex function during meiosis during male germ cells and is linked to mechanisms that inhibit apoptosis.
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