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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.

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