Sources of all-trans retinal oxidation independent of the aldehyde dehydrogenase 1A isozymes exist in the postnatal testis

My-Thanh Beedle; Faith Stevison; Guo Zhong; Traci Topping; Cathryn Hogarth; Nina Isoherranen; Michael D Griswold

doi:10.1093/biolre/ioy200

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Sources of all-trans retinal oxidation independent of the aldehyde dehydrogenase 1A isozymes exist in the postnatal testis

Journal article

Open access

Peer reviewed

Sources of all-trans retinal oxidation independent of the aldehyde dehydrogenase 1A isozymes exist in the postnatal testis

My-Thanh Beedle, Faith Stevison, Guo Zhong, Traci Topping, Cathryn Hogarth, Nina Isoherranen and Michael D Griswold

Biology of reproduction, Vol.100(2), pp.547-560

02/01/2019

DOI: https://doi.org/10.1093/biolre/ioy200

Handle:

https://hdl.handle.net/2376/106958

PMCID: PMC6378859

PMID: 30247516

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https://doi.org/10.1093/biolre/ioy200View

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Abstract

Spermatogonia - drug effects

Gene Expression Regulation, Enzymologic - drug effects

Testis - metabolism

Oxidation-Reduction

Isoenzymes

Aldehyde Dehydrogenase 1 - genetics

Genotype

Male

Mice, Transgenic

Spermatogonia - metabolism

Mice, Knockout

Aldehyde Dehydrogenase 1 - metabolism

Animals

Tretinoin - metabolism

Tamoxifen - pharmacology

Mice

Despite the essential role of the active metabolite of vitamin A, all-trans retinoic acid (atRA) in spermatogenesis, the enzymes, and cellular populations responsible for its synthesis in the postnatal testis remain largely unknown. The aldehyde dehydrogenase 1A (ALDH1A) family of enzymes residing within Sertoli cells is responsible for the synthesis of atRA, driving the first round of spermatogenesis. Those studies also revealed that the atRA required to drive subsequent rounds of spermatogenesis is possibly derived from the ALDH1A enzymes residing within the meiotic and post-meiotic germ cells. Three ALDH1A isozymes (ALDH1A1, ALDH1A2, and ALDH1A3) are present in the testis. Although, ALDH1A1 is expressed in adult Sertoli cells and is suggested to contribute to the atRA required for the pre-meiotic transitions, ALDH1A2 is proposed to be the essential isomer involved in testicular atRA biosynthesis. In this report, we first examine the requirement for ALDH1A2 via the generation and analysis of a conditional Aldh1a2 germ cell knockout and a tamoxifen-induced Aldh1a2 knockout model. We then utilized the pan-ALDH1A inhibitor (WIN 18446) to test the collective contribution of the ALDH1A enzymes to atRA biosynthesis following the first round of spermatogenesis. Collectively, our data provide the first in vivo evidence demonstrating that animals severely deficient in ALDH1A2 postnatally proceed normally through spermatogenesis. Our studies with a pan-ALDH1A inhibitor (WIN 18446) also suggest that an alternative source of atRA biosynthesis independent of the ALDH1A enzymes becomes available to maintain atRA levels for several spermatogenic cycles following an initial atRA injection.

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Title: Sources of all-trans retinal oxidation independent of the aldehyde dehydrogenase 1A isozymes exist in the postnatal testis
Creators: My-Thanh Beedle - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA
Faith Stevison - Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
Guo Zhong - Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
Traci Topping - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA
Cathryn Hogarth - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA
Nina Isoherranen - Department of Pharmaceutics, University of Washington, Seattle, Washington, USA
Michael D Griswold - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA
Publication Details: Biology of reproduction, Vol.100(2), pp.547-560
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: U54 HD042454 / NICHD NIH HHS R01 HD010808 / NICHD NIH HHS T32 GM007750 / NIGMS NIH HHS R01 GM111772 / NIGMS NIH HHS
Identifiers: 99900547066901842
Language: English
Resource Type: Journal article