Expression of Inflammatory and Neurogenic Mediators in Adenomyosis: A Pathogenetic Role

Objective: Adenomyosis is a uterine disorder characterized by dysmenorrhea, dyspareunia, abnormal uterine bleeding, and infertility. Pathogenesis indicates that endometrial cells invade and proliferate within myometrium, and inflammatory mediators participate to the intense painful symptoms. The aim of the present study was to investigate the messenger RNA (mRNA) and protein expression of inflammatory (interleukin 1 beta [IL-1 beta], corticotropin-releasing hormone [CRH], urocortin [Ucn]) and neurogenic (nerve growth factors [NGFs], synaptophysin [SYN], microtubule-associated protein 2 [MAP2]) factors in adenomyotic nodules. Materials and Methods: This prospective study enrolled 16 women, 8 women with nodular adenomyosis and 8 control women undergoing to hysterectomy. Specimens from adenomyotic nodules and eutopic endometrium were collected after surgery. Endometrial tissue was also obtained from the control group and also used for preparing primary culture of human endometrial stromal cells (HESCs). Messenger RNA expression of inflammatory mediators (IL-1 beta, CRH, and Ucn) and neurogenic factors (NGF, SYN, and MAP2) was analyzed by real-time polymerase chain reaction. The in vitro effects of CRH/Ucn on NGF or SYN mRNA expression were also investigated. Results: Adenomyotic nodules highly expressed IL-1 beta, CRH, and Ucn mRNAs, as well as NGF, SYN, and MAP2 mRNAs (P < .001 vs eutopic endometrium and control). Endometrium of women with adenomyosis showed high expression of IL-1b and CRH (P < .001 vs control). Protein expression of CRH, NGF, and SYN in adenomyotic nodules was confirmed by immunohistochemical and immunofluorescence analyses. Urocortin increased NGF mRNA expression in cultured HESCs. Conclusion: The present study showed that adenomyotic nodules are novel site of expression of inflammatory and neurogenic factors, probably involved in the pathogenesis of adenomyosis.