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Published-Ahead-of-Print January 24, 2007, DOI:10.2164/jandrol.106.002006

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Abnormal Morphology of Spermatozoa in Cytochrome P450 17{alpha}-hydroxylase/17, 20-lyase (CYP17) Deficient Mice

Ying Liu , Luis Dettin , Janet Folmer , Barry Zirkin , and Vassilios Papadopoulos *

* To whom correspondence should be addressed. E-mail: papadopv{at}georgetown.edu.

Cytochrome P450 17{alpha}-hydroxylase/17, 20-lyase (CYP17) is crucial for cortisol and sex steroid biosynthesis. In a previous study, we examined CYP17 function by generating knockout mice with a targeted CYP17 deletion. We found that in addition to its role in steroid biosynthesis, CYP17 is present in germ cells. In the present study, we examined the effect of CYP17 on sperm morphology. The disorganization of the sperm midpiece, small sperm mitochondria with reduced inner membranes and matrix, and irregular sperm shape were found to be associated with the CYP17 gene deletion. Treating the mice carrying the CYP17 deletion with testosterone did not alleviate the observed sperm phenotypes, suggesting that CYP17 acts in a testosterone-independent manner. These results suggest that CYP17, in addition to its role androgen formation, is critical for proper mitochondrial architecture and sperm morphology, and thus for sperm function and normal fertility.


Key words: Androgen • Infertility • Sperm • Testis • Steroidogenesis • cytochrome P450s (CYP)






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