Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice

Citation
Wg. Tourtellotte et al., Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice, DEVELOPMENT, 126(22), 1999, pp. 5061-5071
Citations number
55
Categorie Soggetti
Cell & Developmental Biology
Journal title
DEVELOPMENT
ISSN journal
09501991 → ACNP
Volume
126
Issue
22
Year of publication
1999
Pages
5061 - 5071
Database
ISI
SICI code
0950-1991(199911)126:22<5061:IAWISA>2.0.ZU;2-Z
Abstract
Male fertility is complex and depends upon endocrine/paracrine regulatory m echanisms ana morphogenetic processes occurring during testicular developme nt, spermatogenesis (mitosis and meiosis) and spermiogenesis (spermatid mat uration). Egr4 (NGF1-C, pAT133), a member of the Egr family of zinc-finger transcription factors, is thought to be involved in cellular growth and dif ferentiation, but its specific function has been previously unknown. We der ived Egr4 null mice through targeted mutagenesis and found that they were p henotypically normal with the exception that males, but not females, were i nfertile. Egr4 is expressed at low levels within male germ cells during mei osis and is critical for germ cell maturation during the early-mid pachyten e stage. While most Egr4 null male germ cells undergo apoptosis during earl y-mid pachytene, some are capable of maturing beyond an apparent Egr4-depen dent developmental restriction point. Consequently, a limited degree of spe rmiogenesis occurs but this is accompanied by markedly abnormal spermatozoo n morphology and severe oligozoospermia, Egr4 appears to regulate critical genes involved in early stages of meiosis and has a singularly important ro le in male murine fertility. These data raise the possibility that Egr4 may contribute to some forms of human idiopathic male infertility.