Journal of Andrology
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Published-Ahead-of-Print November 22, 2005, DOI:10.2164/jandrol.05133

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Influence of a leptin deficiency on testicular morphology, germ cell apoptosis and expression levels of apoptosis-related genes in the mouse

Ganapathy K. Bhat , Tamika L. Sea , Moshood O. Olatinwo , David Simorangkir , Gregory D. Ford , Byron D. Ford , and David R. Mann *

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

Leptin deficient (ob/ob) male mice are morbidly obese and exhibit impaired reproductive function. The objective of this study was to assess the effect of a leptin deficiency on testicular morphology, germ cell development, apoptotic activity within germ cells and expression levels of apoptosis-related genes in the testis. Sixteen week-old ob/ob male mice (N = 8) and controls (N = 8) were killed and reproductive organs weighed. Testes were processed for either histomorphological analysis (H&E staining), germ cell apoptosis assessment (TUNEL method), or apoptosis-related gene expression analysis (microarray). Cross sections of the testes of leptin deficient animals showed reduced seminiferous tubule area, fewer pachytene spermatocytes and fewer tubules exhibiting elongated spermatids/mature spermatozoa. Condensation of germ cell nuclei and Sertoli cell vacuolization were evident in the testes of some ob/ob animals. Overall there was an elevation of apoptotic activity in the germ cells of ob/ob mice particularly within the pachytene spermatocytes. With microarray technology, we identified nine pro-apoptosis-related genes that were expressed at a significantly higher level in the testes of ob/ob mice compared to controls. Among these were members of the tumor necrosis factor receptor super family 1A and 5 (TNFR1 and 5) and peptidoglycan recognition proteins (associated with the extrinsic apoptotic pathway), and granzymes A and B, growth arrest and DNA damage inducible 45 gamma, sphingosine phosphate lyase 1 and caspase 9 (associated with the intrinsic apoptotic pathway). The results of the current study show that a leptin deficiency in mice is associated with impaired spermatogenesis, increased germ cell apoptosis and up-regulated expression of pro-apoptotic genes within the testes.






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Copyright © 2005 by The American Society of Andrology.