Androglobin, a chimeric mammalian globin, is required for male fertility

Abstract

Spermatogenesis is a highly specialized differentiation process driven by a dynamic gene expression program and ending with the production of mature spermatozoa. Whereas hundreds of genes are known to be essential for male germline proliferation and differentiation, the contribution of several genes remains uncharacterized. The predominant expression of the latest globin family member, androglobin (Adgb), in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape, and ultrastructural defects in microtubule and mitochondrial organization. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifid or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, the absence of Adgb leads to mislocalization of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that Adgb is required for sperm head shaping via the manchette and proper flagellum formation.

Date of acceptance

2022

Autoren

Anna Keppner
Miguel Correia
Sara Santambrogio
Teng Wei Koay
Darko Maric
Carina Osterhof
Denise V Winter
Angèle Clerc
Michael Stumpe
Frédéric Chalmel
Sylvia Dewilde
Alex Odermatt
Dieter Kressler
Thomas Hankeln
Roland H Wenger
David Hoogewijs

DOI

10.7554/elife.72374

eISSN

2050-084X

Zeitschrift

eLife

Sprache

en

Online publication date

2022

Status

Published online

Herausgeber

eLife Sciences Publications, Ltd

Herausgeber URL

http://dx.doi.org/10.7554/elife.72374

Datum der Datenerfassung

2023

Titel

Androglobin, a chimeric mammalian globin, is required for male fertility

Ausgabe der Zeitschrift

11

Datenquelle: Crossref

Abstract

Spermatogenesis is a highly specialized differentiation process driven by a dynamic gene expression program and ending with the production of mature spermatozoa. Whereas hundreds of genes are known to be essential for male germline proliferation and differentiation, the contribution of several genes remains uncharacterized. The predominant expression of the latest globin family member, androglobin (Adgb), in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape, and ultrastructural defects in microtubule and mitochondrial organization. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifid or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, the absence of Adgb leads to mislocalization of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that Adgb is required for sperm head shaping via the manchette and proper flagellum formation.

Addresses

Department of Endocrinology, Metabolism and Cardiovascular system, University of Fribourg, Fribourg, Switzerland.

Autoren

Anna Keppner
Miguel Correia
Sara Santambrogio
Teng Wei Koay
Darko Maric
Carina Osterhof
Denise V Winter
Angèle Clerc
Michael Stumpe
Frédéric Chalmel
Sylvia Dewilde
Alex Odermatt
Dieter Kressler
Thomas Hankeln
Roland H Wenger
David Hoogewijs

DOI

10.7554/elife.72374

eISSN

2050-084X

Externe Identifier

PubMed Identifier: 35700329
PubMed Central ID: PMC9249397

Funding acknowledgements

Deutsche Forschungsgemeinschaft: HA 2103/9-1
Swiss National Science Foundation: 310030_207460
Swiss National Science Foundation: 31003A_173000
Deutsche Forschungsgemeinschaft: HO 5837/1-1
Swiss National Science Foundation: 173000

Open access

true

ISSN

2050-084X

Zeitschrift

eLife

Schlüsselwörter

Testis
Spermatozoa
Sperm Tail
Spermatids
Semen
Animals
Mice, Knockout
Mammals
Mice
Infertility, Male
Globins
Fertility
Male

Sprache

eng

Medium

Electronic

Online publication date

2022

Open access status

Open Access

Paginierung

e72374

Datum der Veröffentlichung

2022

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2022

Titel

Androglobin, a chimeric mammalian globin, is required for male fertility.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

11

Files

https://europepmc.org/articles/PMC9249397?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Spermatogenesis is a highly specialized differentiation process driven by a dynamic gene expression program and ending with the production of mature spermatozoa. Whereas hundreds of genes are known to be essential for male germline proliferation and differentiation, the contribution of several genes remains uncharacterized. The predominant expression of the latest globin family member, androglobin (Adgb), in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape, and ultrastructural defects in microtubule and mitochondrial organization. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifid or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, the absence of Adgb leads to mislocalization of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that Adgb is required for sperm head shaping via the manchette and proper flagellum formation.

Date of acceptance

2022

Autoren

Anna Keppner
Miguel Correia
Sara Santambrogio
Teng Wei Koay
Darko Maric
Carina Osterhof
Denise V Winter
Angèle Clerc
Michael Stumpe
Frédéric Chalmel
Sylvia Dewilde
Alex Odermatt
Dieter Kressler
Thomas Hankeln
Roland H Wenger
David Hoogewijs

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/35700329

DOI

10.7554/eLife.72374

eISSN

2050-084X

Externe Identifier

PubMed Central ID: PMC9249397

Zeitschrift

Elife

Schlüsselwörter

calmodulin
cell biology
developmental biology
globin
heme
infertility
mouse
oxygen
spermatogenesis
Animals
Fertility
Globins
Infertility, Male
Male
Mammals
Mice
Mice, Knockout
Semen
Sperm Tail
Spermatids
Spermatozoa
Testis

Sprache

eng

Country

England

PII

72374

Datum der Veröffentlichung

2022

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2022

Titel

Androglobin, a chimeric mammalian globin, is required for male fertility.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

11

Datenquelle: PubMed

Androglobin, a chimeric mammalian globin, is required for male fertility

Files

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