Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules

Abstract In mammalian testes, undifferentiated spermatogonia (Aundiff) undergo differentiation in response to retinoic acid (RA), while their progenitor states are partially maintained by fibroblast growth factors (FGFs). Sertoli valve (SV) is a region located at the terminal end of seminiferous tub...

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Autores principales: Kasane Imura-Kishi, Aya Uchida, Naoki Tsunekawa, Hitomi Suzuki, Hinako M. Takase, Yoshikazu Hirate, Masami Kanai-Azuma, Ryuji Hiramatsu, Masamichi Kurohmaru, Yoshiakira Kanai
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:8f24b6fde76940158c71023c6e32330f2021-12-02T14:12:42ZLow retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules10.1038/s41598-020-79987-42045-2322https://doaj.org/article/8f24b6fde76940158c71023c6e32330f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79987-4https://doaj.org/toc/2045-2322Abstract In mammalian testes, undifferentiated spermatogonia (Aundiff) undergo differentiation in response to retinoic acid (RA), while their progenitor states are partially maintained by fibroblast growth factors (FGFs). Sertoli valve (SV) is a region located at the terminal end of seminiferous tubule (ST) adjacent to the rete testis (RT), where the high density of Aundiff is constitutively maintained with the absence of active spermatogenesis. However, the molecular and cellular characteristics of SV epithelia still remain unclear. In this study, we first identified the region-specific AKT phosphorylation in the SV Sertoli cells and demonstrated non-cell autonomous specialization of Sertoli cells in the SV region by performing a Sertoli cell ablation/replacement experiment. The expression of Fgf9 was detected in the RT epithelia, while the exogenous administration of FGF9 caused ectopic AKT phosphorylation in the Sertoli cells of convoluted ST. Furthermore, we revealed the SV region-specific expression of Cyp26a1, which encodes an RA-degrading enzyme, and demonstrated that the increased RA levels in the SV region disrupt its pool of Aundiff by inducing their differentiation. Taken together, RT-derived FGFs and low levels of RA signaling contribute to the non-cell-autonomous regionalization of the SV epithelia and its local maintenance of Aundiff in the SV region.Kasane Imura-KishiAya UchidaNaoki TsunekawaHitomi SuzukiHinako M. TakaseYoshikazu HirateMasami Kanai-AzumaRyuji HiramatsuMasamichi KurohmaruYoshiakira KanaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kasane Imura-Kishi
Aya Uchida
Naoki Tsunekawa
Hitomi Suzuki
Hinako M. Takase
Yoshikazu Hirate
Masami Kanai-Azuma
Ryuji Hiramatsu
Masamichi Kurohmaru
Yoshiakira Kanai
Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
description Abstract In mammalian testes, undifferentiated spermatogonia (Aundiff) undergo differentiation in response to retinoic acid (RA), while their progenitor states are partially maintained by fibroblast growth factors (FGFs). Sertoli valve (SV) is a region located at the terminal end of seminiferous tubule (ST) adjacent to the rete testis (RT), where the high density of Aundiff is constitutively maintained with the absence of active spermatogenesis. However, the molecular and cellular characteristics of SV epithelia still remain unclear. In this study, we first identified the region-specific AKT phosphorylation in the SV Sertoli cells and demonstrated non-cell autonomous specialization of Sertoli cells in the SV region by performing a Sertoli cell ablation/replacement experiment. The expression of Fgf9 was detected in the RT epithelia, while the exogenous administration of FGF9 caused ectopic AKT phosphorylation in the Sertoli cells of convoluted ST. Furthermore, we revealed the SV region-specific expression of Cyp26a1, which encodes an RA-degrading enzyme, and demonstrated that the increased RA levels in the SV region disrupt its pool of Aundiff by inducing their differentiation. Taken together, RT-derived FGFs and low levels of RA signaling contribute to the non-cell-autonomous regionalization of the SV epithelia and its local maintenance of Aundiff in the SV region.
format article
author Kasane Imura-Kishi
Aya Uchida
Naoki Tsunekawa
Hitomi Suzuki
Hinako M. Takase
Yoshikazu Hirate
Masami Kanai-Azuma
Ryuji Hiramatsu
Masamichi Kurohmaru
Yoshiakira Kanai
author_facet Kasane Imura-Kishi
Aya Uchida
Naoki Tsunekawa
Hitomi Suzuki
Hinako M. Takase
Yoshikazu Hirate
Masami Kanai-Azuma
Ryuji Hiramatsu
Masamichi Kurohmaru
Yoshiakira Kanai
author_sort Kasane Imura-Kishi
title Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
title_short Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
title_full Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
title_fullStr Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
title_full_unstemmed Low retinoic acid levels mediate regionalization of the Sertoli valve in the terminal segment of mouse seminiferous tubules
title_sort low retinoic acid levels mediate regionalization of the sertoli valve in the terminal segment of mouse seminiferous tubules
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8f24b6fde76940158c71023c6e32330f
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