Submitted February 29, 2008
Returned for revision March 24, 2008
Accepted April 8, 2008
Testis
Age-Dependent Loss of Sperm Production in Mice via Impaired Lysophosphatidic Acid Signaling
Xiaoqin Ye ,
Michael K. Skinner ,
Grace Kennedy ,
and
Jerold Chun *
* To whom correspondence should be addressed. E-mail: jchun{at}scripps.edu.
Abstract
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 whose effects are mediated through at least five G protein-coupled receptors, named LPA1-5. LPA1/2/3, but not LPA4/5, show high expression in mouse testis. Mice deficient for 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 was also 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.
Key words:
Testis •
Spermatogenesis •
LPA and S1P •
germ cell apoptosis and proliferation •
sperm count
