The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice.
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.
Rainey
Mark A
MA
Eppley Institute for Research in Cancer and Allied Diseases, UNMC-Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska, USA.
George
Manju
M
Ying
GuoGuang
G
Akakura
Reiko
R
Burgess
Daniel J
DJ
Siefker
Ed
E
Bargar
Tom
T
Doglio
Lynn
L
Crawford
Susan E
SE
Todd
Gordon L
GL
Govindarajan
Venkatesh
V
Hess
Rex A
RA
Band
Vimla
V
Naramura
Mayumi
M
Band
Hamid
H
D000818:Animals; D004705:Endocytosis; D005260:Female; D007248:Infertility, Male / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
C485640:Ehd1 protein, mouse; D033921:Vesicular Transport Proteins