Extracellular matrix remodeling and inflammatory pathway in human endometrium: insights from uterine leiomyomas

The endometrium of women with type 3 leiomyoma exhibits differential expression of metalloproteinases, their inhibitors, and interleukins. This observation indicates a different endometrial molecular profile that may impair endometrial receptivity.

VOLUME 116, ISSUE 5, P1404-1414


Laura Governini, Ph.D., Camilla Marrocco, Ph.D., Bianca Semplici, Ph.D., Valentina Pavone, Ph.D., Giuseppe Belmonte, B.Sc., Stefano Luisi, Ph.D., Felice Petraglia, M.D., Alice Luddi, Ph.D., Paola Piomboni, Ph.D.



To compare the expression profiles of matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases, TIMPs) in the endometrium of women with and without type 3 leiomyomas and to understand their relationship with inflammatory status.


Molecular and in silico studies.


University hospital.


Patients with type 3 leiomyomas ranging from 3 to 10 cm in diameter (n = 18) and control age-matched women undergoing surgery for ovarian cysts (n = 18) who underwent endometrial biopsies.


Endometrial biopsies.

Main Outcome Measure(s)

To evaluate the expression levels of MMPs and TIMPs in the endometrium, quantitative reverse transcriptase polymerase chain reaction and Western blot were performed. With the use of immunofluorescence analysis, the investigated proteins were localized in the tissues. The expression levels of inflammatory mediators such as IL-1β, IL-6, IL-10, TGF, COX1, COX2, STAT3, and VEGF were evaluated by quantitative reverse transcriptase polymerase chain reaction, and their relationships were detected by the STRING approach.


The endometrium of women with type 3 leiomyomas exhibited differential expression of MMPs and TIMPs, particularly MMP2, MMP11, and MMP14, as well as different topographic distribution, suggesting that leiomyomas may influence the endometrial molecular profile. Significant decreases in IL-1β, IL-6, and IL-10 expression, along with increases in COX1 and COX2, as well as VEGF, were highlighted. The STRING approach suggests that this altered gene expression profile may affect the Th17 cell differentiation pathway.


The differential expression and localization of MMPs and TIMPs observed in women with type 3 leiomyomas, along with the reported derangement in the expression of key molecules involved in the inflammatory pathway, may contribute to changes in endometrial receptivity in these patients.