title: Regeneration of Leydig cells in ectopically autografted adult mouse testes.
abstract: Ectopic autografting of testis tissue is a promising approach for studying testicular development, male germline preservation and restoration of male fertility. In this study, we examined the fate of various testicular cells in adult mouse testes following ectopic autografting at 1, 2, 4 and 8 weeks post grafting. Histological examination showed no evidence of re-establishment of spermatogenesis in autografts, and progressive degeneration of seminiferous tubules was detected. Expression of germ cell-specific proteins such as POU5F1, DAZL, TNP1, TNP2, PRM1 and PRM2 revealed that, although proliferating and differentiating spermatogenic germ cells such as spermatogonia, spermatocytes and spermatids could survive in autografts until 4 weeks, only terminally differentiated germ cells such as sperm persisted in autografts until 8 weeks. The presence of Sertoli and peritubular myoid cells, as indicated by expression of WT1 and ACTA2 proteins, respectively, was evident in the autografts until 8 weeks. Interestingly, seminal vesicle weight and serum testosterone level were restored in autografted mice by 8 weeks post grafting. The expression of Leydig cell-specific proteins such as CYP11A1, HSD3B2 and LHCGR showed revival of Leydig cell (LC) populations in autografts over time since grafting. Elevated expression of PDGFRA, LIF, DHH and NEFH in autografts indicated de novo regeneration of LC populations. Autografted adult testis can be used as a model for investigating Leydig cell regeneration, steroidogenesis and regulation of the intrinsic factors involved in Leydig cell development. The success of this rodent model can have therapeutic applications for adult human males undergoing sterilizing cancer therapy.
authors.affiliation: Laboratory for the Conservation of Endangered SpeciesCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
authors.forename: Himesh
authors.initials: H
authors.lastname: Makala
authors.affiliation: Laboratory for the Conservation of Endangered SpeciesCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Pothana
authors.affiliation: Laboratory for the Conservation of Endangered SpeciesCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
authors.forename: Surabhi
authors.initials: S
authors.lastname: Sonam
authors.affiliation: Laboratory for the Conservation of Endangered SpeciesCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Malla
authors.affiliation: Laboratory for the Conservation of Endangered SpeciesCentre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India sandeep@ccmb.res.in.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Goel
mesh_terms: D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D007985:Leydig Cells / Q000502:physiology*; D008297:Male; D051379:Mice; D011375:Progesterone Reductase / Q000378:metabolism; D011479:Protamines / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000502:physiology / Q000637:transplantation*; D013739:Testosterone / Q000097:blood
chemical_list: D011479:Protamines; C068621:protamine 2; D013739:Testosterone; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D002786:Cholesterol Side-Chain Cleavage Enzyme