Journal of Andrology
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Published-Ahead-of-Print February 5, 2009, DOI:10.2164/jandrol.108.006122

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Sexual Development and Fertility of Loxl1-/- Male Mice

Hadley M. Wood , Una J. Lee , Drina Vurbic , Edmund Sabanegh , Jonathan H. Ross , Tiansen Li , and Margot S. Damaser *

* To whom correspondence should be addressed. E-mail: damasem{at}ccf.org.

Our objective was to investigate the genitourinary defects and fertility of the male Loxl1 knock-out (Loxl1-/-) mouse, with particular attention to fecundity and testicular, epididymal, gubernacular and penile histopathology, which may lead us to a better understanding of the role of the elastin-homeostasis gene, LOXL1, in male sexual development. Genital morphometric evaluation of 6-9 month-old male Loxl1-/- (N=26) mice were compared with C57Bl/6 controls (N=24). Measurements included: body weight, scrotal development, evidence of feminization (nipples or vaginal pouch), penile malformations, anogenital distance (AGD), and absence/presence and size of perineal bulge. Sperm production was estimated using a standardized technique. A breeding program was conducted to determine how much of the infertility observed in Loxl1-/- pairs was due to the male factor. Finally, we performed histopathological comparison of the genitourinary organs of Loxl1-/- and control mice. Loxl1-/- mice weighed less than their age-matched C57Bl/6 counterparts (P<0.001). Size-adjusted perineal bulge was larger (P<0.001) and resting location of the gonads were higher intraabdominally (P=0.048) in the Loxl1-/- mice. Estimates of daily sperm counts revealed that the Loxl1-/- mice had lower sperm production (P=0.048). Loxl1-/- males bred with control females demonstrated relative fecundity values intermediate between Loxl1-/- pairs (lowest fecundity) and control pairs (highest fecundity), suggesting a component of male-factor infertility. No histological differences were noted using H&E or specialized elastin staining of the gonads, gubernaculum and penis. While further studies are warranted, these findings suggest a subtle, likely multifactorial, role of the LOXL1 protein in male sexual development and fertility.



Key words: Fertility • Penis • Reproductive Tract • Semen Analysis • Testis • Elastin • <it>Loxl1</it> • Mouse model




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