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9 July 2022 Sertoli cell PUMILIO proteins modulate mouse testis size through translational control of cell cycle regulators
Tingting Zhao, Tianheng Xiao, Dandan Cao, Wenjuan Xia, Liuze Gao, Liping Cheng, Min Zang, Xin Li, Eugene Yujun Xu
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Abstract

Testis size determination is an important question of reproductive biology. Sertoli cells are known to be a key determinant of mammalian testis size but the underlying molecular mechanisms remain incompletely understood. Previously we showed that highly conserved germ cell RNA-binding proteins, PUMILIO1(PUM1) and PUMILIO2 (PUM2), control mouse organ and body size through translational regulation, but how different cell types of the organs contribute to their organ size regulation has not been established. Here, we report a somatic role of PUM in gonad size determination. PUM1 is highly expressed in the Sertoli cells of the developing testis from embryonic and postnatal mice as well as in germ cells. Removal of Sertoli cell, but not germ cell, Pum1 gene, led to reduced testis size without significantly affecting sperm number or fertility. Knockout of PUM1 target, Cdkn1b, rescued the phenotype of reduced testis size, supporting a key role of Sertoli cell PUM1 mediated Cdkn1b repression in the testis size control. Furthermore, removal of Pum2 or both Pum1 and Pum2 in the Sertoli cells also only affected the testis size, not sperm development, with the biggest size reduction in Pum1/2 double knockout mice. We propose that PUM1 and PUM2 modulate the testis size through their synergistic translational regulation of cell cycle regulators in the Sertoli cell. Further investigation of the ovary or other organs could reveal if PUM-mediated translational control of cell proliferation of the supporting cell represents a general mechanism for organ size modulation.

Summary Sentence

PUM1 and PUM2 modulate mouse testis size through their synergistic translational regulation of cell cycle regulators in Sertoli cells.

Graphical Abstract

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© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Tingting Zhao, Tianheng Xiao, Dandan Cao, Wenjuan Xia, Liuze Gao, Liping Cheng, Min Zang, Xin Li, and Eugene Yujun Xu "Sertoli cell PUMILIO proteins modulate mouse testis size through translational control of cell cycle regulators," Biology of Reproduction 107(1), 135-147, (9 July 2022). https://doi.org/10.1093/biolre/ioac118
Received: 6 January 2022; Accepted: 31 May 2022; Published: 9 July 2022
JOURNAL ARTICLE
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KEYWORDS
CDKN1b
gonadal somatic cells
gonadogenesis
organ size
PUF
PUM
RNA-binding protein
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