@article{19ebb5b0daca49d28dce1109faca40fb,
title = "The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice",
abstract = "Background. 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 Ehd1 -/- mice using a Cre/loxP system. Results. Both male and female Ehd1-/- mice survived at sub-Mendelian ratios. A proportion of Ehd1-/- mice were viable and showed smaller size at birth, which continued into adulthood. Ehd1-/- adult males were infertile and displayed decreased testis size, whereas Ehd1-/- females were fertile. In situ 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 Ehd1 -/- 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 Ehd1-/- males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in Ehd1-/- mice. Conclusions. 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.",
author = "Rainey, {Mark A.} and Manju George and Guoguang Ying and Reiko Akakura and Burgess, {Daniel J.} and Ed Siefker and Tom Bargar and Lynn Doglio and Crawford, {Susan E.} and Todd, {Gordon L.} and Venkatesh Govindarajan and Hess, {Rex A.} and Vimla Band and Mayumi Naramura and Hamid Band",
note = "Funding Information: We thank Donna Emge (Jameson Lab, Northwestern Univ.) for technical advice with fixation, embedding and preparations of testis sections; Drs. Jeffrey Weiss (Northwestern Univ.), J. Larry Jameson (Northwestern Univ.), Erv Goldberg (Northwestern Univ.), Qing Zhou (Griswold Lab at Washington State Univ.) and members of the Band Labs for helpful discussions and comments, the UNMC Comparative Medicine Core Facility for providing professional animal husbandry and veterinary care, Anita Jennings (Histology Core Facility at UNMC), Karen Dulany and Maureen Harmon (Eppley Histology Laboratory) for technical assistance and the Core Electron Microscopy Research Facility at UNMC. This work was supported by: the NIH grants CA105489, CA87986, CA116552, and CA99163 to HB, CA94143, CA96844 and CA81076 to VB, and EY017610 to VG; Department of Defense Breast Cancer Research Grants W81XVVH-08-1-0617 (HB) and DAMD17-02-1-0508 (VB); the Jean Ruggles-Romoser Chair of Cancer Research (HB) and the Duckworth Family Chair of Breast Cancer Research (VB). MN was a an ENH Research Career Development Awardee, GY an Arthur Michel, M.D. Fellow for Breast Cancer Research at ENH, and MAR a trainee of the National Institutes of Health Grant T32 CA70085 to the Robert H. Lurie Comprehensive Cancer Center Training Program in Signal Transduction and Cancer. The Histology Core at the UNMC-Eppley Cancer Center is supported by an NCI Cancer Center Core Grant. The University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core is supported by the Eunice Kennedy Shriver NICHD/NIH (SCCPIR) Grant U54-HD28934. The authors declare no potential conflicts of interest.",
year = "2010",
doi = "10.1186/1471-213X-10-37",
language = "English (US)",
volume = "10",
journal = "BMC Developmental Biology",
issn = "1471-213X",
publisher = "BioMed Central",
}