ARS | Publication request: Ghrelin and leptin interplay in prevention of testicular damage due to cryptochidism

Submitted to: Journal of Urology
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2009
Publication Date: August 1, 2009
Citation: Alukal, J.P., Whirledge, S., Louet, M., Sun, Y., Smith, R.G., Lamb, D.J. 2009. Ghrelin and leptin interplay in prevention of testicular damage due to cryptochidism [abstract]. Journal of Urology. 181 (Suppl.4): 683.

Technical Abstract: Ghrelin, the endogenous ligand to the growth hormone secretagogue receptor (ghsr), is centrally implicated in body weight homeostasis. A novel murine model for ghrelin and its physiologic antagonist, leptin, was developed at this institution. Mice with a deletion of ghsr (ghsr -/-) or a targeted disruption of ghrelin were crossed to the leptin-deficient background (ob/ob). Wild-type, ob/ob, ghrelin -/-, ob/ob//ghrelin -/- (DKO) and ob-r//ghsr -/- (DKOR) mice were examined for testis histology, location, and eugonadal state. Male ob/ob animals were obese, hypogonadal, cryptorchid, and infertile; both male DKO and DKOR animals, despite also being obese, cryptorchid, and hypogonadal, were observed to have intact spermatogenesis. We hypothesize that intact fertility in male DKO and DKOR animals is independent of a) androgen status and b) testicular descent. This implies an alternate pathway by which ghrelin regulates spermatogenesis. Three month old male animals were laparotomized; testis location, size and epididymal weight were recorded. Hemotoxylin and eosin staining of testis sections was performed. Serum testosterone was assayed with blood taken at time of sacrifice. mRNA was isolated from homogenized whole testes using a kit-based protocol (RNEasy, Qiagen). Quantitative PCR was performed in a standard fashion using TaqMan Universal PCR chemistry Applied Biosystems). Gene-specific primers and probes were designed using Primer Express software (Applied Biosystems). All qPCR results were generated in duplicate; samples were run in triplicate. Statistical analysis was performed using ANOVA (SPSS v. 15.0, SPSS, Inc.). Testis location in DKO, DKOR, and ob/ob animals was cryptorchid. H&E staining of DKO and DKOR testis showed predominantly normal spermatogenesis; ob/ob animals showed either empty seminiferous tubules or early arrest of spermatogenesis and Leydig cell atrophy. Serum testosterone was lower in the ob/ob, DKO and DKOR mice, although this was variable. Analysis of 14 testis specific genes (and GAPDH) revealed extensive differences in relative gene expression; twofold differences or greater achieved statistical significance. Intact spermatogenesis in DKO and DKOR animals occurs despite a) hypogonadism and b) intraabdominal testis location. Leptin and ghrelin appear to maintain spermatogenesis even in spite of testis undescent. Gene expression profiling will identify signaling pathways by which this phenomenon can be modulated.