Sertoli Cell Number Defines and Predicts Germ and Leydig Cell Population Sizes in the Adult Mouse Testis

Abstract Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin−mediated cell ablation to reduce Sertoli c...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2017-09, Vol.158 (9), p.2955-2969
Main Authors: Rebourcet, Diane, Darbey, Annalucia, Monteiro, Ana, Soffientini, Ugo, Tsai, Yi Ting, Handel, Ian, Pitetti, Jean-Luc, Nef, Serge, Smith, Lee B, O’Shaughnessy, Peter J
Format: Article
Language:English
Subjects:
Aging
Aging - physiology
Animal models
Animals
Cell Count
Cell culture
Cell Differentiation
Cell number
Cell size
Diphtheria
Diphtheria toxin
Diphtheria Toxin - genetics
Endocrinology
Fertility
Genes, Transgenic, Suicide
Germ cells
Germ Cells - cytology
Germ Cells - physiology
Growth and Development - physiology
Leydig cells
Leydig Cells - cytology
Leydig Cells - physiology
Male
Mathematical models
Mice
Mice, Transgenic
Peptide Fragments - genetics
Population
Population number
Population studies
Prediction models
Rodents
Sertoli cells
Sertoli Cells - cytology
Sertoli Cells - physiology
Sexual Maturation - physiology
Spermatogenesis - physiology
Spermatozoa - cytology
Spermatozoa - physiology
Testis - cytology
Testis - metabolism
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Summary:Abstract Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin−mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the Sertoli cell population that forms during development determines the number of germ cells and Leydig cells that will be present in the adult testis. Similarly, the number of germ cells and Leydig cells that can be maintained in the adult depends directly on the size of the adult Sertoli cell population. Finally, we have used linear modeling to generate predictive models of testis cell composition during development and in the adult based on the size of the Sertoli cell population. This study shows that at all ages the size of the Sertoli cell population is predictive of resulting testicular cell composition. A reduction in Sertoli cell number/proliferation at any age will therefore lead to a proportional decrease in germ cell and Leydig cell numbers, with likely consequential effects on fertility and health. Sertoli cell knockout studies show that the numbers of Leydig cells and germ cells that develop and are maintained in the testis are directly proportional to the number of Sertoli cells.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2017-00196