The Effect of Mesenchymal Stem Cells on Fertility in Experimental Retrocervical Endometriosis

Abstract

Purpose To evaluate the effect of mesenchymal stem cells (MSCs) on fertility in experimental retrocervical endometriosis. Methods A total of 27 New Zealand rabbits were divided into three groups: endometriosis, in which endometrial implants were created; mesenchymal, in which MSCs were applied in addition to the creation of endometrial implants; and control, the group without endometriosis. Fisher's exact test was performed to compare the dichotomous qualitative variables among the groups. The quantitative variables were compared by the nonparametric Mann-Whitney and Kruskal-Wallis tests. The MannWhitney test was used for post-hoc multiple comparison with Boniferroni correction. Results Regarding the beginning of the fertile period, the three groups had medians of 14 AE 12.7, 40 AE 5, and 33 AE 8.9 days respectively (p ¼ 0.005). With regard to fertility (number of pregnancies), the endometriosis and control groups showed a rate of 77.78%, whereas the mesenchymal group showed a rate of 11.20% (p ¼ 0.015). No differences in Keenan's histological classification were observed among the groups (p ¼ 0.730). With regard to the macroscopic appearance of the lesions, the mesenchymal group showed the most pelvic adhesions. Conclusion The use of MSCs in endometriosis negatively contributed to fertility, suggesting the role of these cells in the development of this disease.

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies

“…Although BMDCs decreased in situ TNF-α and VEGFR levels, they did not affect lesion size [264]. In another study, bone marrow-derived MSCs were injected locally into an endometriotic implant in a rabbit endometriosis model [265]. The MSC group had significantly more intra-abdominal adhesions and a lower pregnancy rate than did the control group, and no reduction in implant size with MSC treatment was noted [265].…”

“…In another study, bone marrow-derived MSCs were injected locally into an endometriotic implant in a rabbit endometriosis model [265]. The MSC group had significantly more intra-abdominal adhesions and a lower pregnancy rate than did the control group, and no reduction in implant size with MSC treatment was noted [265]. When human umbilical cord mesenchymal stem cells were used to treat cultured endometriotic cells, the cytokine expression of IL-1β and proliferation rate of endometriotic cells increased in vitro [266].…”

Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis

“…It inhibits PI3K/AKT signaling by converting PIP3 to PIP2 . Of particular interest to endometriosis is its ability in maintaining genomic stability …”

“…140 Of particular interest to endometriosis is its ability in maintaining genomic stability. [143][144][145] In endometriosis, the first attempt to evaluate PTEN mutation yielded negative results, 146 but the other study reported a mutation frequency of 21% (7/34) in OMA. 147 One study found no mutation at PTEN (0/23), 87 but the negative finding may be simply attributable to lack of adequate statistical power due to moderate sample size.…”

Malignant Transformation and Associated Biomarkers of Ovarian Endometriosis: A Narrative Review

“…PTEN inhibits PI3K/AKT signaling by converting phosphatidylinositol (3,4,5)trisphosphate (PIP3) to phosphatidylinositol 4,5-bisphosphate (PIP2) [146]. Of particular interest to endometriosis is its ability to maintain genomic stability [147][148][149]. In endometriosis, the first attempt to evaluate PTEN mutation yielded negative results [150], but another study reported a mutation frequency of 21% (7/34) in endometriomas [99].…”