Potency of testicular somatic environment to support spermatogenesis in XX/Sry transgenic male mice.
The sex-determining region of Chr Y (Sry) gene is sufficient to induce testis formation and the subsequent male development of internal and external genitalia in chromosomally female mice and humans. In XX sex-reversed males, such as XX/Sry-transgenic (XX/Sry) mice, however, testicular germ cells always disappear soon after birth because of germ cell-autonomous defects. Therefore, it remains unclear whether or not Sry alone is sufficient to induce a fully functional testicular soma capable of supporting complete spermatogenesis in the XX body. Here, we demonstrate that the testicular somatic environment of XX/Sry males is defective in supporting the later phases of spermatogenesis. Spermatogonial transplantation analyses using XX/Sry male mice revealed that donor XY spermatogonia are capable of proliferating, of entering meiosis and of differentiating to the round-spermatid stage. XY-donor-derived round spermatids, however, were frequently detached from the XX/Sry seminiferous epithelia and underwent cell death, resulting in severe deficiency of elongated spermatid stages. By contrast, immature XY seminiferous tubule segments transplanted under XX/Sry testis capsules clearly displayed proper differentiation into elongated spermatids in the transplanted XY-donor tubules. Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed the missing expression of several Y-linked genes and the alterations in the expression profile of genes associated with spermiogenesis. Therefore, our findings indicate dysfunction of the somatic tubule components, probably Sertoli cells, of XX/Sry testes, highlighting the idea that Sry alone is insufficient to induce a fully functional Sertoli cell in XX mice.
Ishii
Mayuko
M
Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Tokyo, Japan.
Tachiwana
Tsuyoshi
T
Hoshino
Anshin
A
Tsunekawa
Naoki
N
Hiramatsu
Ryuji
R
Matoba
Shogo
S
Kanai-Azuma
Masami
M
Kawakami
Hayato
H
Kurohmaru
Masamichi
M
Kanai
Yoshiakira
Y
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D012734:Disorders of Sex Development; D005260:Female; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012671:Seminiferous Tubules / Q000637:transplantation; D012708:Sertoli Cells / Q000502:physiology; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology*; D013093:Spermatogonia / Q000637:transplantation; D013737:Testis / Q000503:physiopathology*
D017931:DNA Primers; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse