Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice

Manju George, Mark A. Rainey, Mayumi Naramura, GuoGuang Ying, Don W. Harms, Martha H. Vitaterna, Lynn Doglio, Susan E. Crawford, Rex A. Hess, Vimla Band, Hamid Band

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulate endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4-/- mice confirmed EHD4 deletion. Ehd4-/- mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (Day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (Day 31) were seen in the Ehd4-/- testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium, and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4-/- males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and EHD4 levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1 in the adult Ehd4-/- testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of postmitotic and postmeiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function.

Original languageEnglish (US)
Pages (from-to)328-342
Number of pages15
JournalGenesis
Volume48
Issue number5
DOIs
StatePublished - May 1 2010

Fingerprint

Fertility
Testis
Germ Cells
Apoptosis
Seminiferous Epithelium
Gene Knockout Techniques
Seminiferous Tubules
Spermatocytes
Sperm Count
Spermatids
Western Blotting
Head
Cell Proliferation
Weights and Measures
Polymerase Chain Reaction
Protein Domains
DNA

Keywords

  • Compensation
  • EHD proteins
  • Endocytic recycling
  • Functional redundancy
  • Testis spermatogenesis

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice. / George, Manju; Rainey, Mark A.; Naramura, Mayumi; Ying, GuoGuang; Harms, Don W.; Vitaterna, Martha H.; Doglio, Lynn; Crawford, Susan E.; Hess, Rex A.; Band, Vimla; Band, Hamid.

In: Genesis, Vol. 48, No. 5, 01.05.2010, p. 328-342.

Research output: Contribution to journalArticle

George, M, Rainey, MA, Naramura, M, Ying, G, Harms, DW, Vitaterna, MH, Doglio, L, Crawford, SE, Hess, RA, Band, V & Band, H 2010, 'Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice', Genesis, vol. 48, no. 5, pp. 328-342. https://doi.org/10.1002/dvg.20620
George, Manju ; Rainey, Mark A. ; Naramura, Mayumi ; Ying, GuoGuang ; Harms, Don W. ; Vitaterna, Martha H. ; Doglio, Lynn ; Crawford, Susan E. ; Hess, Rex A. ; Band, Vimla ; Band, Hamid. / Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice. In: Genesis. 2010 ; Vol. 48, No. 5. pp. 328-342.
@article{20e3d0b3fd0f49b0a9367afc723531db,
title = "Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice",
abstract = "The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulate endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4-/- mice confirmed EHD4 deletion. Ehd4-/- mice were viable and born at expected Mendelian ratios; however, males showed a 50{\%} reduction in testis weight, obvious from postnatal day 31. An early (Day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (Day 31) were seen in the Ehd4-/- testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium, and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4-/- males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and EHD4 levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1 in the adult Ehd4-/- testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of postmitotic and postmeiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function.",
keywords = "Compensation, EHD proteins, Endocytic recycling, Functional redundancy, Testis spermatogenesis",
author = "Manju George and Rainey, {Mark A.} and Mayumi Naramura and GuoGuang Ying and Harms, {Don W.} and Vitaterna, {Martha H.} and Lynn Doglio and Crawford, {Susan E.} and Hess, {Rex A.} and Vimla Band and Hamid Band",
year = "2010",
month = "5",
day = "1",
doi = "10.1002/dvg.20620",
language = "English (US)",
volume = "48",
pages = "328--342",
journal = "Genesis",
issn = "1526-954X",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Ehd4 is required to attain normal prepubertal testis size but dispensable for fertility in male mice

AU - George, Manju

AU - Rainey, Mark A.

AU - Naramura, Mayumi

AU - Ying, GuoGuang

AU - Harms, Don W.

AU - Vitaterna, Martha H.

AU - Doglio, Lynn

AU - Crawford, Susan E.

AU - Hess, Rex A.

AU - Band, Vimla

AU - Band, Hamid

PY - 2010/5/1

Y1 - 2010/5/1

N2 - The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulate endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4-/- mice confirmed EHD4 deletion. Ehd4-/- mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (Day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (Day 31) were seen in the Ehd4-/- testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium, and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4-/- males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and EHD4 levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1 in the adult Ehd4-/- testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of postmitotic and postmeiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function.

AB - The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulate endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4-/- mice confirmed EHD4 deletion. Ehd4-/- mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (Day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (Day 31) were seen in the Ehd4-/- testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium, and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4-/- males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and EHD4 levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1 in the adult Ehd4-/- testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of postmitotic and postmeiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function.

KW - Compensation

KW - EHD proteins

KW - Endocytic recycling

KW - Functional redundancy

KW - Testis spermatogenesis

UR - http://www.scopus.com/inward/record.url?scp=77952046067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952046067&partnerID=8YFLogxK

U2 - 10.1002/dvg.20620

DO - 10.1002/dvg.20620

M3 - Article

C2 - 20213691

AN - SCOPUS:77952046067

VL - 48

SP - 328

EP - 342

JO - Genesis

JF - Genesis

SN - 1526-954X

IS - 5

ER -