Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling

Xiaoqin Ye; Michael K Skinner; Grace Kennedy; Jerold Chun

doi:10.1095/biolreprod.108.068783

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Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling

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Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling

Xiaoqin Ye, Michael K Skinner, Grace Kennedy and Jerold Chun

Biology of reproduction, Vol.79(2), pp.328-336

08/2008

DOI: https://doi.org/10.1095/biolreprod.108.068783

Handle:

https://hdl.handle.net/2376/108682

PMID: 18448840

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Abstract

Receptors, Lysophosphatidic Acid - metabolism

Sperm Count

Testis - metabolism

Cell Proliferation

Spermatogenesis - genetics

Age Factors

Receptors, Lysophosphatidic Acid - genetics

Spermatozoa - metabolism

Sexual Behavior, Animal - physiology

Testosterone - blood

Testis - cytology

Mice, Inbred C57BL

Signal Transduction - genetics

Mice, Knockout

Spermatogenesis - physiology

Mitogen-Activated Protein Kinase 3 - metabolism

Signal Transduction - physiology

Spermatozoa - physiology

Spermatozoa - cytology

Lysophospholipids - physiology

Phosphorylation

Approximately half of all infertility cases can be attributed to male reproductive dysfunction for which low sperm count is a major contributing factor. The current study identified receptor-mediated lysophosphatidic acid (LPA) signaling as a new molecular component influencing male fertility. LPA is a small signaling phospholipid, the effects of which are mediated through at least five G protein-coupled receptors, named LPA 1-5. LPA1/2/3, but not LPA4/5, show high expression in mouse testis. Mice deficient in LPA1/2/3 showed a testosterone-independent reduction of mating activity and sperm production, with an increased prevalence of azoospermia in aging animals. A significant increase of germ cell apoptosis also was observed in testes. Germ cell apoptosis led to a reduction in germ cell proliferation. These data demonstrate a novel in vivo function for LPA signaling as a germ cell survival factor during spermatogenesis.

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Title: Age-dependent loss of sperm production in mice via impaired lysophosphatidic acid signaling
Creators: Xiaoqin Ye - Department of Molecular Biology, The Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA
Michael K Skinner
Grace Kennedy
Jerold Chun
Publication Details: Biology of reproduction, Vol.79(2), pp.328-336
Academic Unit: Biological Sciences, School of
Publisher: United States
Grant note: R01 HD050685-01A1 / NICHD NIH HHS R01 HD050685 / NICHD NIH HHS
Identifiers: 99900547799601842
Language: English
Resource Type: Accepted manuscript