Lack of GBA2: A contraceptive for male mice

Although it had previously been thought that a protein known as GBA2 was important for bile acid metabolism, a new study appearing in the November issue of the Journal of Clinical Investigation shows that in mice GBA2 is in fact required for male fertility. This study might explain the contraceptive effect in mice of a treatment for humans lacking the related protein GBA1 and could lead to the development of a new male contraceptive.

To gain insight into the function of GBA2, David Russell and colleagues generated mice lacking GBA2. Surprisingly, given that it had been proposed that GBA2 had a role in regulating a key step in the metabolism of bile acid, bile acid metabolism in these mice occurred normally. Instead, male mice lacking GBA2 showed decreased fertility. This was because the sperm from these mice had abnormally large, round heads, and were fewer in number and moved more slowly than sperm from normal mice.

Individuals lacking the GBA2 related protein GBA1 suffer from Gaucher's disease (a disease that causes various symptoms, including enlarged internal organs and neurologic defects) and one treatment for this disease has been shown to decrease fertility in mice. This study, identifying a crucial role in male fertility for GBA2, might help explain the effect on fertility of this treatment for Gaucher's disease and, as Martin Matzuk and colleagues explain in an accompanying commentary, might help further the development of a nonhormonal male contraceptive pill.

TITLE: Mutation of beta-glucosidase 2 causes glycolipid storage disorder disease and impaired male fertility

AUTHOR CONTACT:

David W. Russell
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Phone: (214) 648-2007; Fax (214) 648-6899; E-mail: david.russell@utsouthwestern.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=29224

ACCOMPANYING COMMENTARY

TITLE: Shaping the sperm head: an ER enzyme leaves its mark

AUTHOR CONTACT:

Martin M. Matzuk
Baylor College of Medicine, Houston, Texas, USA.
Phone: (713) 798-6451; Fax: (713) 798-5833; E-mail: mmatzuk@bcm.tmc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=30221