Differential expression of neuregulin 1 (NRG1) and candidate miRNA regulating NRG1 transcription in the chicken oviduct in response to hormonal changes

Neuregulin 1 (NRG1), a signaling protein that binds to members of the erythroblastoma (ErbB) family, is known to play essential biological roles in mediating cell-cell interactions and orchestrating vital cell functions in the heart and nervous system. NRG1 is closely associated with developmental processes in various organs and expression of several NRG1 isoforms are regulated by estrogen. However, NRG1 expression and its hormonal regulation during development of the female reproductive tract remain unknown. The reproductive system of chickens undergoes dynamic morphological and functional changes in response to estrogen and the molting process. Therefore, in the current study, we found differential expression of NRG1 and candidate microRNA regulating chicken NRG1 transcription in response to estrogen stimulation and/or the molting process. The results revealed that relative expression of NRG1 mRNA increased in the oviducts of chicks treated with diesthylstilbestrol (DES; a synthetic non- steroidal estrogen). Additionally, abundant NRG1 mRNA expression was primarily in the glandular (GE) and luminal (LE) epithelia of the magnum in the developing chick oviduct in response to exogenous estrogen. Also, NRG1 expression decreased during regression of the oviduct following induced molting by feeding high levels of zinc in the diet, and then gradually resurged as the oviduct underwent remodeling and recrudescence in laying hens. In addition, the present results revealed changes in relative expression of candidate chicken microRNA (miR-222a, miR-222b-3p and miR-1611) targeting NRG1 transcription in chicken oviducts in response to exogenous estrogen. In conclusion, these results provide the first evidence that NRG1 is a novel estrogen-responsive gene closely correlated with the estrogen-dependent development of the oviduct of chicks and regeneration of the oviduct after molting. Further, regulation of NRG1 expression involving at least 3 chicken miRNA is likely a prerequisite for those estrogen regulated developmental events.