CREBZF expression and hormonal regulation in the mouse uterus

Pengfei Lin,Fenglei Chen,Xiao Li,Aihua Wang,Jinhua Zhou,Xiangguo Wang,Nan Wang,Yaping Jin

doi:10.1186/1477-7827-11-110

Pengfei Lin, Fenglei Chen + Show 6 more

Open Access

https://doi.org/10.1186/1477-7827-11-110

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Abstract

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

Highlights

CREBZF is a member of the mammalian Activating transcription factor (ATF)/cAMP-response-element-binding protein (CREB) family of the basic region-leucine zipper transcription factors
These results indicated that SMILE was the predominant form in this study, whereas Zhangfei was not detected in the mouse uterus
Localisation of SMILE in mouse embryos during the peri-implantation period To further study the role of SMILE in embryo implantation, we examined its localisation in the mouse embryos from the zygote to the blastocyst stage

Summary

Introduction

CREBZF is a member of the mammalian ATF/CREB family of the basic region-leucine zipper (bZIP) transcription factors. Zhangfei was first identified via its interaction with the Herpes Simplex Virus-1 (HSV-1)-related cellular protein Host Cell Factor 1 (HCF-1) and has been proposed to play a role in inhibiting the replication of the herpes simplex virus [2,5]. Recent studies have shown that Zhangfei could potentially play an important role in the mammalian unfolded protein response (UPR) [6,7,8]. SMILE has been reported as a novel transcriptional co-regulator of a variety of nuclear receptors, including oestrogen receptors, glucocorticoid receptor, constitutive androstane receptor, hepatocyte nuclear factor 4α and oestrogen receptor-related receptor γ [3,12,13]. To explore the potential function of CREBZF during pregnancy, we sought to investigate in detail the expression and regulation of CREBZF mRNA and protein in the mouse uterus during the oestrous cycle and peri-implantation period

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