Is matrix metalloproteinase required in postnatal testicular tubules for germ cell maturation?

• Published in: Journal of pediatric surgery Vol. 47; no. 9; pp. 1724 - 1729
• Main Authors: Li, Ruili, Zhang, Jian-Guo, Churchill, James, Sourial, Magdy, Southwell, Bridget R, Hutson, John M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2012
• Subjects: Animals; Anti-Mullerian Hormone - metabolism; Biomarkers - metabolism; Cell Movement; Cryptorchidism; DEAD-box RNA Helicases - metabolism; Extracellular Matrix - physiology; Gonocyte transformation; Immunoblotting; Infertility; Male; Matrix metalloproteinase; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase 2 - metabolism; Microscopy, Confocal; MT1-MMP; Pediatrics; Rats; Rats, Sprague-Dawley; Receptors, Androgen - metabolism; Spermatogenesis - physiology; Spermatogonia - physiology; Surgery; Testis - embryology; Testis - metabolism; Testis - physiology; TIMP2; Tissue Inhibitor of Metalloproteinase-2 - metabolism; TIMP2; Cryptorchidism; MT1-MMP; Gonocyte transformation; Matrix metalloproteinase; Infertility
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2012.03.062

Abstract Background/Aim Cryptorchidism may cause infertility by failed transformation of neonatal gonocytes into adult dark spermatogonia, the putative stem cells for spermatogenesis. Gonocytes migrate centrifugally to the tubular basement membrane to become adult dark spermatogonia. Regulation of this transformation remains unknown. We aimed to investigate neonatal rodent testis matrix metalloproteinase (MMP) production to see whether MMPs loosen extracellular matrix between Sertoli cells to facilitate gonocyte movement. Methods Sprague-Dawley rat testes (n = 4-6 per group) were collected at embryonic day 19 (E19) and postnatal (P) days P0 to 10 for immunohistochemistry. Immunofluorescent confocal images were captured for presence of membrane type 1 MMP (MT1-MMP), matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 2 (TIMP2), mouse VASA homologue, anti-Müllerian hormone, and androgen receptor in tissue sections. Testicular proteins were analyzed by immunoblotting. Results Membrane type 1 MMP was strongly present in gonocytes at E19 then decreased, whereas it increased in testicular somatic cells from P0 to P10. Testicular protein levels of MT1-MMP, MMP2, and androgen receptor were constant from E19 to P10. Anti-Müllerian hormone protein sharply decreased after P2, whereas TIMP2 gradually increased from E19 to P10. Gonocytes migrated to basement membrane at P2 to P6. Conclusion Membrane type 1 MMP, MMP2, and TIMP2 were present in testis from E19 to P10 during gonocyte migration and transformation into spermatogenic stem cells. Increased knowledge about germ cell development may aid efforts to improve fertility in cryptorchidism.