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Publication : Inactivation of AMPKα1 induces asthenozoospermia and alters spermatozoa morphology.

First Author  Tartarin P Year  2012
Journal  Endocrinology Volume  153
Issue  7 Pages  3468-81
PubMed ID  22581459 Mgi Jnum  J:189041
Mgi Id  MGI:5444092 Doi  10.1210/en.2011-1911
Citation  Tartarin P, et al. (2012) Inactivation of AMPKalpha1 induces asthenozoospermia and alters spermatozoa morphology. Endocrinology 153(7):3468-81
abstractText  AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit alpha1 gene [alpha1AMPK knockout (KO)]. In the testis, the alpha1AMPK subunit is expressed in germ cells and also in somatic cells (Sertoli and Leydig cells). alpha1AMPK KO male mice show a decrease in fertility, despite no clear alteration in the testis morphology or sperm production. However, in alpha1AMPK(-/-) mice, we demonstrate that spermatozoa have structural abnormalities and are less motile than in control mice. These spermatozoa alterations are associated with a 50% decrease in mitochondrial activity, a 60% decrease in basal oxygen consumption, and morphological defects. The alpha1AMPK KO male mice had high androgen levels associated with a 5- and 3-fold increase in intratesticular cholesterol and testosterone concentrations, respectively. High concentrations of proteins involved in steroid production (3beta-hydroxysteroid dehydrogenase, cytochrome steroid 17 alpha-hydroxylase/17,20 lysate, and steroidogenic acute regulatory protein) were also detected in alpha1AMPK(-/-) testes. In the pituitary, the LH and FSH concentrations tended to be lower in alpha1AMPK(-/-) male mice, probably due to the negative feedback of the high testosterone levels. These results suggest that total alpha1AMPK deficiency in male mice affects androgen production and quality of spermatozoa, leading to a decrease in fertility.
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