Submitted February 13, 2008
Returned for revision February 28, 2008
Accepted March 10, 2008
Gamete Biology
Expression of the Gene for Mouse Lactate Dehydrogenase C (Ldhc) Is Required for Male Fertility
Fanny Odet ,
Chongwen Duan ,
William D. Willis ,
Eugenia H. Goulding ,
Aisha Kung ,
Edward M. Eddy ,
and
Erwin Goldberg *
* To whom correspondence should be addressed. E-mail: erv{at}northwestern.edu.
Abstract
The lactate dehydrogenase (LDH) protein family members characteristically are distributed in tissue- and cell-type specific patterns and serve as the terminal enzyme of glycolysis, catalyzing reversible oxidation-reduction between pyruvate and lactate. They are present as tetramers and one family member, LDHC, is abundant in spermatocytes, spermatids, and sperm, but also is found in modest amounts in oocytes. We disrupted the Ldhc gene to determine whether LDHC is required for spermatogenesis, oogenesis, and/or sperm and egg function. The targeted disruption of Ldhc severely impaired fertility in male Ldhc-/- mice, but not in female Ldhc-/- mice. Testis and sperm morphology and sperm production appeared to be normal. However, total LDH enzymatic activity was considerably lower in Ldhc-/- sperm than in wild type sperm, indicating that the LDHC homotetramer (LDH-C4) is responsible for most of the LDH activity in sperm. Although initially motile when isolated, there was a more rapid reduction in the level of ATP and in motility in Ldhc-/- sperm than in wild type sperm. Moreover, Ldhc-/- sperm did not acquire hyperactivated motility, were unable to penetrate the zona pellucida in vitro, and failed to undergo the phosphorylation events characteristic of capacitation. These studies showed that LDHC plays an essential role in maintenance of the processes of glycolysis and ATP production in the flagellum that are required for male fertility and sperm function.
Key words:
Gamete Biology •
Sperm •
Sperm capacitation •
Sperm motility and transport
