Abstract
Recently a system was developed in which transplanted donor spermatogonial stem cells establish complete spermatogenesis in the testes of an infertile recipient. To obtain insight into stem cell activity and the behavior of donor germ cells, the pattern and kinetics of mouse spermatogonial colonization in recipient seminiferous tubules were analyzed during the 4 mo following transplantation. The colonization process can be divided into three continuous phases. First, during the initial week, transplanted cells were randomly distributed throughout the tubules, and a small number reached the basement membrane. Second, from 1 wk to 1 mo, donor cells on the basement membrane divided and formed a monolayer network. Third, beginning at about 1 mo and continuing throughout the observation period, cells in the center of the network differentiated extensively and established a colony of spermatogenesis, which expanded laterally by repeating phase two and then three. An average of 19 donor cell-derived colonies developed from 10(6) cells transplanted to the seminiferous tubules of a recipient testis; the number of colonized sites did not change between 1 and 4 mo. However, the length of the colonies increased from 0.73 to 5.78 mm between 1 and 4 mo. These experiments establish the feasibility of studying in a systematic and quantitative manner the pattern and kinetics of the colonization process. Using spermatogonial transplantation as a functional assay, it should be possible to assess the effects of various treatments on stem cells and on recipient seminiferous tubules to provide unique insight into the process of spermatogenesis.
MeSH Terms
Animals
Cell Division
Kinetics
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Seminiferous Tubules/cytology
Spermatogenesis
Spermatogonia/cytology,transplantation
Stem Cell Transplantation
Stem Cells/cytology
Testis/cytology
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Nagano M
School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6009, USA.
Avarbock M R
Brinster R L
References (23)
23 references, click to expand
-
Spermatogenesis following male germ-cell transplantation.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11298-302
PMID: 7972053
-
Growth and differentiation of spermatogenetic colonies in the mouse testis after irradiation with fission neutrons.
Radiat Res. 1983 Jun;94(3):447-63
PMID: 6856784
-
Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization.
J Cell Biol. 1977 Jul;74(1):68-85
PMID: 874003
-
Spermatogenetic clones developing from repopulating stem cells surviving a high dose of an alkylating agent.
Cell Tissue Kinet. 1975 Nov;8(6):543-51
PMID: 1238171
-
Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap strain leads to widespread expression of beta-galactosidase in mouse embryos and hematopoietic cells.
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3789-94
PMID: 9108056
-
Ultrastructural observations of spermatogenesis in mice resulting from transplantation of mouse spermatogonia.
J Androl. 1996 Nov-Dec;17(6):603-14
PMID: 9016390
-
A direct measurement of the radiation sensitivity of normal mouse bone marrow cells.
Radiat Res. 1961 Feb;14:213-22
PMID: 13776896
-
Culture of mouse spermatogonial stem cells.
Tissue Cell. 1998 Aug;30(4):389-97
PMID: 9787472
-
Development of germ cell transplants in mice.
Biol Reprod. 1998 Dec;59(6):1360-70
PMID: 9828179
-
The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation.
Anat Rec. 1971 Mar;169(3):533-57
PMID: 5550532
-
Growth of spermatogenetic colonies in the mouse testis after irradiation with fission neutrons.
Radiat Res. 1982 Jan;89(1):150-65
PMID: 7038739
-
Nonrandom distribution of mouse spermatogonial stem cells surviving fission neutron irradiation.
Radiat Res. 1986 Jul;107(1):11-23
PMID: 3737874
-
Morphological and quantitative analysis of spermatogonia in mouse testes using whole mounted seminiferous tubules. II. The irradiated testes.
Anat Rec. 1978 Dec;192(4):529-42
PMID: 736273
-
Competitive repopulation: a new assay for long-term stem cell functional capacity.
Blood. 1980 Jan;55(1):77-81
PMID: 6985804
-
Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal.
Physiol Rev. 1972 Jan;52(1):198-236
PMID: 4621362
-
Transplantation of testis germinal cells into mouse seminiferous tubules.
Int J Dev Biol. 1997 Feb;41(1):111-22
PMID: 9074943
-
Definition of the stages of the cycle of the seminiferous epithelium in the rat.
Ann N Y Acad Sci. 1952 Nov 20;55(4):548-73
PMID: 13139144
-
Probability of self-renewing divisions of spermatogonial stem cells in colonies, formed after fission neutron irradiation.
Cell Tissue Kinet. 1990 Jan;23(1):1-16
PMID: 2302729
-
Spermatogonial transplantation and reconstitution of donor cell spermatogenesis in recipient mice.
APMIS. 1998 Jan;106(1):47-55; discussion 56-7
PMID: 9524561
-
Germline transmission of donor haplotype following spermatogonial transplantation.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11303-7
PMID: 7972054
-
Gradual regeneration of mouse testicular stem cells after exposure to ionizing radiation.
Radiat Res. 1978 May;74(2):349-62
PMID: 149333
-
Effects of busulfan on murine spermatogenesis: cytotoxicity, sterility, sperm abnormalities, and dominant lethal mutations.
Mutat Res. 1987 Feb;176(2):259-68
PMID: 3807936
-
Radiation survival and regeneration characteristics of spermatogenic stem cells of mouse testis.
Radiat Res. 1974 Jan;57(1):88-103
PMID: 10874929