Am J Physiol Cell Physiol AJP: Gastrointestinal and Liver Physiology
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Am J Physiol Cell Physiol 293: C305-C312, 2007. First published May 2, 2007; doi:10.1152/ajpcell.00608.2006
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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Reduced urea flux across the blood-testis barrier and early maturation in the male reproductive system in UT-B-null mice

Lirong Guo,1,* Dan Zhao,1,2,* Yuanlin Song,2 Yan Meng,1 Huashan Zhao,1 Xuejian Zhao,1 and Baoxue Yang2

1Research Center of Prostate Diseases, Department of Reproductive Pathophysiology, School of Basic Medicine, Jilin University, Changchun, Jilin province, China; and 2Department of Medicine, University of California, San Francisco, California

Submitted 6 December 2006 ; accepted in final form 28 April 2007

A urea-selective urine-concentrating defect was found in transgenic mice deficient in urea transporter (UT)-B. To determine the role of facilitated urea transport in extrarenal organs expressing UT-B, we studied the kinetics of [14C]urea distribution in UT-B-null mice versus wild-type mice. After renal blood flow was disrupted, [14C]urea distribution was selectively reduced in testis in UT-B-null mice. Under basal conditions, total testis urea content was 335.4 ± 43.8 µg in UT-B-null mice versus 196.3 ± 18.2 µg in wild-type mice (P < 0.01). Testis weight in UT-B-null mice (6.6 ± 0.8 mg/g body wt) was significantly greater than in wild-type mice (4.2 ± 0.8 mg/g body wt). Elongated spermatids were observed earlier in UT-B-null mice compared with wild type mice on day 24 versus day 32, respectively. First breeding ages in UT-B knockout males (48 ± 3 days) were also significantly earlier than that in wild-type males (56 ± 2 days). In competing mating tests with wild-type males and UT-B-null males, all pups carried UT-B-targeted genes, which indicates that all pups were produced from breeding of UT-B-null males. Experiments of the expression of follicle-stimulating hormone receptor (FSHR) and androgen binding protein (ABP) indicated that the development of Sertoli cells was also earlier in UT-B-null mice than that in wild-type mice. These results suggest that UT-B plays an important role in eliminating urea produced by Sertoli cells and that UT-B deletion causes both urea accumulation in the testis and early maturation of the male reproductive system. The UT-B knockout mouse may be a useful experimental model to define the molecular mechanisms of early puberty.

urea transporter; Sertoli cell; testis; male sexual function; spermatogenesis



Address for reprint requests and other correspondence: B. Yang, 1246 Health Sciences East Tower, Univ. of California, San Francisco, CA 94143-0521 (e-mail: Baoxue.Yang{at}ucsf.edu) or X. Zhao, Dept. of Reproductive Pathophysiology, School of Basic Medicine, Jilin Univ., Changchun, 130021, Jilin province, China (e-mail: pro_2{at}jlu.edu.cn)







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