Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro

Oleksandr Kirsanov; Taylor Johnson; Taylor Malachowski; Bryan A. Niedenberger; Emma A. Gilbert; Debajit Bhowmick; P. Hande Ozdinler; Douglas A. Gray; Kelsey Fisher-Wellman; Brian P. Hermann; Christopher B. Geyer

doi:10.1242/dev.200713

Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro

Oleksandr Kirsanov, Taylor Johnson, Taylor Malachowski, Bryan A. Niedenberger, Emma A. Gilbert, Debajit Bhowmick, P. Hande Ozdinler, Douglas A. Gray, Kelsey Fisher-Wellman, Brian P. Hermann, Christopher B. Geyer^*

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

In mammalian testes, premeiotic spermatogonia respond to retinoic acid by completing an essential lengthy differentiation program before initiating meiosis. The molecular and cellular changes directing these developmental processes remain largely undefined. This wide gap in knowledge is due to two unresolved technical challenges: (1) lack of robust and reliable in vitro models to study differentiation and meiotic initiation; and (2) lack of methods to isolate large and pure populations of male germ cells at each stage of differentiation and at meiotic initiation. Here, we report a facile in vitro differentiation and meiotic initiation system that can be readily manipulated, including the use of chemical agents that cannot be safely administered to live animals. In addition, we present a transgenic mouse model enabling fluorescence-activated cell sorting-based isolation of millions of spermatogonia at specific developmental stages as well as meiotic spermatocytes.

Original language	English (US)
Article number	dev200713
Journal	Development (Cambridge)
Volume	149
Issue number	22
DOIs	https://doi.org/10.1242/dev.200713
State	Published - Nov 2022

Funding

The authors thank Joani Zary-Oswald (director of the Brody School of Medicine Histology Core Facility) for technical assistance, Leslie Heckert for anti-DMRT1, and the late Dr Stuart Moss (former program officer, Eunice Kennedy Shriver National Institute of Child Health and Human Development) for helpful discussions and for encouraging us to complete this study to make it easier for laboratories in the future to study all aspects of mammalian spermatogenesis. Funding This work was supported by grants from the National Institutes of Health (NIH; HD090083 and HD105963 to C.B.G.; HD090007 to B.P.H.) as well as a Fellowship from the Male Contraceptive Initiative (to O.K.). The study was also supported in part by NIH instrumentation grant S10-OD021615. Open Access funding provided by East Carolina University. Deposited in PMC for immediate release. This work was supported by grants from the National Institutes of Health (NIH; HD090083 and HD105963 to C.B.G.; HD090007 to B.P.H.) as well as a Fellowship from the Male Contraceptive Initiative (to O.K.). The study was also supported in part by NIH instrumentation grant S10-OD021615. Open Access funding provided by East Carolina University. Deposited in PMC for immediate release.

Keywords

Meiosis
Spermatocytes
Spermatogenesis
Spermatogonia
Testis

ASJC Scopus subject areas

Molecular Biology
Developmental Biology

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10.1242/dev.200713

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title = "Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro",

abstract = "In mammalian testes, premeiotic spermatogonia respond to retinoic acid by completing an essential lengthy differentiation program before initiating meiosis. The molecular and cellular changes directing these developmental processes remain largely undefined. This wide gap in knowledge is due to two unresolved technical challenges: (1) lack of robust and reliable in vitro models to study differentiation and meiotic initiation; and (2) lack of methods to isolate large and pure populations of male germ cells at each stage of differentiation and at meiotic initiation. Here, we report a facile in vitro differentiation and meiotic initiation system that can be readily manipulated, including the use of chemical agents that cannot be safely administered to live animals. In addition, we present a transgenic mouse model enabling fluorescence-activated cell sorting-based isolation of millions of spermatogonia at specific developmental stages as well as meiotic spermatocytes.",

keywords = "Meiosis, Spermatocytes, Spermatogenesis, Spermatogonia, Testis",

author = "Oleksandr Kirsanov and Taylor Johnson and Taylor Malachowski and Niedenberger, {Bryan A.} and Gilbert, {Emma A.} and Debajit Bhowmick and Ozdinler, {P. Hande} and Gray, {Douglas A.} and Kelsey Fisher-Wellman and Hermann, {Brian P.} and Geyer, {Christopher B.}",

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AU - Gilbert, Emma A.

AU - Bhowmick, Debajit

AU - Ozdinler, P. Hande

AU - Gray, Douglas A.

AU - Fisher-Wellman, Kelsey

AU - Hermann, Brian P.

AU - Geyer, Christopher B.

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Modeling mammalian spermatogonial differentiation and meiotic initiation in vitro

Abstract

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Keywords

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