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

Patrizia Carrarelli, Chih-Feng Yen, Chih‐Feng Yen, Lucia Funghi, Felice Arcuri, Claudia Tosti, Giuseppe Bifulco, Alice Luddi, Chyi‐Long Lee, Chyi-Long Lee, Felice Petraglia
Reproductive sciences (Thousand Oaks, Calif.) · 2016 · vol. 24(3) , pp. 369–375 · doi:10.1177/1933719116657192 · PMID:27440813 · W2500246545
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⚙ AI-generated summary by claude@2026-06+body, 2026-06-06 ⓘ

Adenomyotic nodules express higher levels of inflammatory and neurogenic mediators like IL-1β, CRH, Ucn, and NGF compared to eutopic endometrium.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-06 · read from full text ⓘ

This prospective study examined inflammatory mediators (IL-1β, CRH, urocortin) and neurogenic markers (NGF, synaptophysin, MAP2) in adenomyotic nodules and eutopic endometrium from 16 women undergoing hysterectomy (8 with nodular adenomyosis, 8 controls), using real-time PCR for mRNA and immunohistochemical/immunofluorescence methods for protein confirmation. Adenomyotic nodules showed markedly higher expression of both inflammatory and neurogenic factors compared with eutopic endometrium and control tissues (P<.001), and the adenomyosis-associated endometrium specifically had higher IL-1β and CRH expression versus control. In cultured human endometrial stromal cells, urocortin increased NGF mRNA expression, supporting an in vitro regulatory link. The main limitation is the small sample size (n=16) and the correlative nature of tissue expression, with limited functional validation beyond the urocortin→NGF effect in vitro. This paper is centrally about endometriosis and/or adenomyosis—adenomyosis—specifically demonstrating inflammatory and neurogenic mediator expression in adenomyotic nodules and proposing a pathogenetic role.

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Abstract

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 1β [IL-1β], 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-1β, 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-1β, 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-1β 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. Similar content being viewed by others

References

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Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Carrarelli, P., Yen, CF., Funghi, L. et al. Expression of Inflammatory and Neurogenic Mediators in Adenomyosis: A Pathogenetic Role. Reprod. Sci. 24, 369–375 (2017). https://doi.org/10.1177/1933719116657192 Published: Issue date: DOI: https://doi.org/10.1177/1933719116657192

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adenomyosis

MeSH descriptors

Adenomyosis Corticotropin-Releasing Hormone Interleukin-1beta Microtubule-Associated Proteins Nerve Growth Factors Synaptophysin Urocortins Uterus Adenomyosis Adenomyosis Corticotropin-Releasing Hormone Corticotropin-Releasing Hormone Endometrium Endometrium Female Humans Interleukin-1beta Interleukin-1beta Microtubule-Associated Proteins Microtubule-Associated Proteins

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