Modulation of germ cell apoptosis with a nitric oxide synthase inhibitor in a murine model of congenital cryptorchidism

The Journal of Urology
William R DeFoorAlfor G Lewis

Abstract

Apoptosis has been implicated in testicular germ cell loss in experimental models of cryptorchidism. Nitric oxide synthase (NOS) has been shown to have a role in apoptosis in many cell types. The Hoxa 11 knockout mouse has congenital bilateral cryptorchidism and is uniformly sterile. We examined the time course of apoptosis in this model and attempted to attenuate this response in vivo by inhibition of NOS. The offspring of heterozygous Hoxa 11 knockout mice were genotyped by polymerase chain reaction. Homozygous knockout mice treated with the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and untreated controls were sacrificed at weekly intervals at 3 to 13 weeks of age. Spermatogenesis was evaluated with hematoxylin and eosin staining. Germ cell apoptosis was assessed with a TUNEL assay and DNA staining. Co-localization of NOS activity was measured with a polyclonal antibody to endothelial NOS. Impaired spermatogenesis was observed in Hoxa 11 knockout mice. Testis/body weight ratios were decreased in this group at weeks 6 and 7, while body weights were unchanged. Germ cell apoptosis was significantly higher in the knockout group compared to wild-type controls. Co-localization was observed between endothelial NOS ...Continue Reading

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Citations

Oct 2, 2009·Oxidative Medicine and Cellular Longevity·Nikki P Y Lee, C Yan Cheng
Sep 26, 2012·Cellular and Molecular Life Sciences : CMLS·Byunghyuk KimKunsoo Rhee
Apr 28, 2007·Acta Paediatrica·Anders Bergh, Olle Söder
Feb 15, 2011·International Journal of Experimental Pathology·Rosa María Vigueras-VillaseñorJulio César Rojas-Castañeda
Aug 18, 2004·The Urologic Clinics of North America·Thomas F KolonDale S Huff
May 29, 2016·Journal of Theoretical Biology·Nafiseh SedaghatAli Shojaie
Oct 2, 2014·BMC Complementary and Alternative Medicine·Woong Jin BaeSae Woong Kim
Jul 16, 2008·Acta histochemica·Rosa María Vigueras-VillaseñorJulio César Rojas-Castañeda
Nov 21, 2012·Nature Reviews. Urology·Ashok AgarwalSandro C Esteves
Jun 9, 2020·Molecular Reproduction and Development·Jungbin Yoon, Kunsoo Rhee

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis