CREBZF expression and hormonal regulation in the mouse uterus

CREBZF is a member of the mammalian ATF/CREB family of the basic region-leucine zipper (bZIP) transcription factors. Two isoforms of CREBZF have been identified from the alternative usage of initiation codons, SMILE (long isoform of CREBZF) and Zhangfei (short isoform of CREBZF). Until recently, the physiological function of CREBZF in mammalian reproductions has not been reported.

Multiple techniques were performed to investigate the spatiotemporal expression and hormonal regulation of the CREBZF gene in the mouse uterus and its role in embryo implantation.

Zhangfei was not detected in the mouse uterus. SMILE immunostaining was mainly expressed in the uterine luminal and glandular epithelium, and the expression levels of both SMILE mRNA and protein gradually decreased from days 1-3 of pregnancy, peaked on day 4, and then declined again on day 6. On day 5 of pregnancy, SMILE protein expression was detected only in the luminal epithelium at implantation sites compared with the expression at inter-implantation sites. SMILE protein was not detected in decidual cells from days 6-8 of pregnancy or artificial decidualisation. Furthermore, SMILE protein was not detected in the mouse uterus on days 3-6 of pseudopregnancy, and SMILE expression was also induced in the delayed-implantation uterus, indicating that the presence of an active blastocyst was required for SMILE expression at the implantation site. Oestrogen significantly stimulated SMILE expression in the ovariectomised mouse uterus. In addition, in cycling mice, high levels of SMILE protein and mRNA expression were also observed in proestrus and oestrus uteri.

Taken together, these results suggested that SMILE expression was closely related to mouse implantation and up-regulated by oestrogen.