Interleukin-6 regulates expression of Fos and Jun genes to affect the development of mouse preimplantation embryos

Abstract

Aim: We investigated whether recombinant mouse interleukin-6 (IL-6) affects the development of preimplantation embryos and induces the -signal transducers and activators of transcription (JAK-STAT) signaling pathway by binding IL-6 signal transducer (IL-6st) and regulating Fos and Jun gene expression, thereby accounting for the negative effect of superovulation on embryo development.

Methods: We compared rates of blastocyst formation from embryos cultured with different concentrations of IL-6 or/and anti-interleukin 6 receptor antibody (anti-IL-6RAb) in superovulated experimental and normal control groups. IL-6 expression in preimplantation embryos was determined by immunofluorescence identification. Fos, Jun and IL-6st messenger RNA expression was detected by PCR and microarray experiments.

Results: Rates of blastocyst formation significantly decreased in superovulated embryos, whether or not they were incubated in 0.1, 1, 25 or 50 pg/mL IL-6, (P < 0.01) compared to embryos from naturally ovulated controls, whereas incubation in 5 and 10 pg/mL IL-6 reversed the negative effects of superovulation. The addition of anti-IL-6RAb to naturally ovulated embryos reduced blastocyst rates to those of superovulated embryos. Gene chip analysis indicated that the JAK-STAT signaling pathway contained differentially expressed IL-6, IL-6st, Jun and Fos genes. Both anti-IL-6RAb or ovarian stimulation downregulated IL-6st, Jun, and Fos messenger RNA expression, but expression of the same three genes increased in 5 pg/mL IL-6.

Conclusion: Ovarian stimulation negatively impacts the development of preimplantation embryos by reducing IL-6 release. IL-6 affects the rate of development of zygotes to blastocyst by regulating IL-6st, Fos and Jun expression in the JAK-STAT signaling pathway.

Keywords: Fos; IL-6; Jun; embryo; mouse; ovarian stimulation; preimplantation.