References
Query Results -- Details
MGI Accession ID: MGI:2667445
J Number: J:84347
Other Accession IDs:
Title: Functional role of inducible nitric oxide synthase in the induction of male germ cell apoptosis, regulation of sperm number, and determination of testes size: evidence from null mutant mice.
Authors: Lue Y; Sinha Hikim AP; Wang C; Leung A; Swerdloff RS
Journal: Endocrinology
Volume: 144
Issue: 7
Date: 2003 Jul
Year: 2003
Pages: 3092-100
Review Status: Peer Reviewed
Abstract:
Inducible nitric oxide synthase (iNOS) through its product, nitric oxide (NO), may contribute to the induction of germ cell apoptosis. Using adult iNOS-deficient mice, we characterized the reproductive hormonal profile and the testicular phenotype. Although there was no difference in body weight, mean testis weights in mutant mice were 30.77% higher, and testicular sperm count was 65.51% higher than control animals. No significant differences were apparent in plasma LH, FSH, and testosterone levels between these mice. Compared with wild-type mice, histomorphometric analysis showed that the mutant mice had a 39.63% increase in the number of pachytene spermatocytes and 33.79% in round spermatids, with no apparent changes in the number of preleptotene spermatocytes and spermatogonia. The incidence of spontaneous germ cell apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay was lower at stages I-IV and XI-XII of iNOS-mutant mice compared with wild-type animals. The rate of germ cell proliferation estimated by quantitative assessment of the bromodeoxyuridine labeled preleptotene spermatocytes showed no significant change between wild-type and iNOS-deficient mice. When applying testicular warming (43 C for 15 min) to mice, the rate of germ cell apoptosis was elevated predominantly at early (I-IV) and late (XI-XII) stages, and less during stages V-VI, VII-VIII, and IX-X at 2 and 6 h after heat exposure in the wild-type mice. In contrast, the rate of apoptosis in mutant mice was markedly decreased at early and late stages 2 and 6 h after heat exposure. Pachytene spermatocytes and early round spermatids were most susceptible to heat-induced apoptosis in both mutant and control animals. Our studies demonstrate that: 1) deficiency of iNOS results in failure to eliminate a small portion of pachytene spermatocytes and round spermatids by apoptosis, resulting in a remarkable increase in testis weight and sperm output; 2) deficiency of iNOS confers partial resistance to heat-induced germ cell apoptosis. These experiments suggest that iNOS plays a physiological role in regulation of germ cell number and in determining testicular size.
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