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Expression of Inflammatory and Neurogenic Mediators in Adenomyosis: 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.

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Author information

Authors and Affiliations

  1. Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Policlinico “Santa Maria alle Scotte,” Viale Bracci, 53100, Siena, Italy

    Patrizia Carrarelli, Lucia Funghi, Felice Arcuri, Claudia Tosti, Alice Luddi & Felice Petraglia MD

  2. Department of Obstetrics and Gynecology, Linkou Chang Gung Memorial Hospital, Tao-Yuan, Taiwan

    Chih-Feng Yen MD, PhD

  3. Chang Gung University College of Medicine, Taoyuan, Taiwan

    Chih-Feng Yen MD, PhD & Chyi-Long Lee MD, PhD

  4. Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taipei, Taiwan

    Chih-Feng Yen MD, PhD

  5. Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, Naples, Italy

    Giuseppe Bifulco

  6. Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

    Chyi-Long Lee MD, PhD

Authors
  1. Patrizia Carrarelli
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  2. Chih-Feng Yen MD, PhD
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  3. Lucia Funghi
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  4. Felice Arcuri
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  5. Claudia Tosti
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  6. Giuseppe Bifulco
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  7. Alice Luddi
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  8. Chyi-Long Lee MD, PhD
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  9. Felice Petraglia MD
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Corresponding author

Correspondence to Felice Petraglia MD.

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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

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  • DOI: https://doi.org/10.1177/1933719116657192

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