Wg. Tourtellotte et al., Infertility associated with incomplete spermatogenic arrest and oligozoospermia in Egr4-deficient mice, DEVELOPMENT, 126(22), 1999, pp. 5061-5071
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.