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Postnatal germ cell development during minipuberty in the mouse does not require androgen receptor: implications for managing cryptorchidism

Journal
The Journal of Urology
Publisher
Elsevier
Identifiers
DOI: 10.1016/j.juro.2014.10.024
Keywords
Disciplines
  • Chemistry
License
Unknown

Abstract

Abstract Purpose Undescended testis (UDT) leads to infertility and malignancy resulting from aberrant germ cell (GC) development. Androgens are proposed to control early GC development during the transient postnatal surge of gonadotropins and androgen, known as mini-puberty. We aim to assess the effect of androgen receptor on perinatal GC development in mice. Material and Methods Testes from androgen receptor knockout (ARKO) mice and wild type (WT) littermates (n=3-4/group) were collected at embryonic day E17 and postnatal days P0 (birth), P2, P4, P6, P8 and P10 for immunohistochemistry. Antibodies against mouse VASA homologue (MVH, GC maker), anti-Műllerian hormone (AMH, Sertoli cell marker), Ki-67 (proliferating cell marker), and DAPI (nuclei) were used and visualized by confocal microscopy. The numbers of GC/tubule, GC on the tubular basement membrane (GC/BM), Sertoli cells/tubule and the percentage of proliferating GC (Ki67+)/tubule and GC (Ki67+)/BM on confocal images were counted using image J. Data were analyzed using nonparametric one-way ANOVA with GraphPad Prism 5.02. Results In both WT and ARKO testes, GC/tubule decreased from E17 -P2, then increased normally. Number of MVH+ GC/tubule and GC on the BM were similar in ARKO and WT testes (p>0.05) at each age, and the percentages of proliferating GC (Ki-67+)/tubule and proliferating GC/BM were similar at each age (p>0.05). Conclusions Androgen receptor are nor required for gonocyte migration from centre of testicular tubules to BM, and transformation into spermatogonia stem cells up to day 10 in ARKO mice. Identifying non-androgenic factors might improve fertility potential of boys with UDT and undergoing orchidopexy.

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