The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice

• Main Authors: Hess Rex A, Govindarajan Venkatesh, Todd Gordon L, Crawford Susan E, Doglio Lynn, Bargar Tom, Burgess Daniel J, Siefker Ed, Akakura Reiko, Ying GuoGuang, George Manju, Rainey Mark A, Band Vimla, Naramura Mayumi, Band Hamid
• Format: Article
• Language: English
• Published: BMC 2010-04-01
• Series: BMC Developmental Biology
• Online Access: http://www.biomedcentral.com/1471-213X/10/37

<p>Abstract</p> <p>Background</p> <p>The C-terminal Eps15 homology domain-containing protein 1 (EHD1) is ubiquitously expressed and regulates the endocytic trafficking and recycling of membrane components and several transmembrane receptors. To elucidate the function of EHD1 in mammalian development, we generated <it>Ehd1</it>^-/-mice using a Cre/<it>loxP </it>system.</p> <p>Results</p> <p>Both male and female <it>Ehd1</it>^-/-mice survived at sub-Mendelian ratios. A proportion of <it>Ehd1</it>^-/-mice were viable and showed smaller size at birth, which continued into adulthood. <it>Ehd1</it>^-/-adult males were infertile and displayed decreased testis size, whereas <it>Ehd1</it>^-/-females were fertile. <it>In situ </it>hybridization and immunohistochemistry of developing wildtype mouse testes revealed EHD1 expression in most cells of the seminiferous epithelia. Histopathology revealed abnormal spermatogenesis in the seminiferous tubules and the absence of mature spermatozoa in the epididymides of <it>Ehd1</it>^-/-males. Seminiferous tubules showed disruption of the normal spermatogenic cycle with abnormal acrosomal development on round spermatids, clumping of acrosomes, misaligned spermatids and the absence of normal elongated spermatids in <it>Ehd1</it>^-/-males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in <it>Ehd1</it>^-/-mice.</p> <p>Conclusions</p> <p>Contrary to a previous report, these results demonstrate an important role for EHD1 in pre- and post-natal development with a specific role in spermatogenesis.</p>