Effects of pharmacological inhibition of hyaluronic acid synthesis on experimental endometriosis

OLIVARES, CARLA NOEMÍ; RICCI, ANALÍA GABRIELA; BILOTAS, MARIELA ANDREA; ALANIZ, LD; BARAÑAO, ROSA INÉS; MERESMAN, GABRIELA FABIANA

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2022

0014-2972

Background: Hyaluronic acid (HA) has been shown to be implicated in several pathological conditions including endometriosis. 4-Methylumbelliferone (4MU) is an HA synthesis inhibitor with proven antitumor activity. In this study we aim to evaluate the effect of 4MU on endometriosis development both in vivo and in vitro.Methods: Endometriosis was surgically induced in 32 two-month-old BALB/c mice. Animals were designated into the early or late starting treatment group, which initiated on day 2 or on day 15 after endometriosis induction surgery, respectively. Within each of these groups, 200 mg/kg 4MU or 200 µl vehicle (Control) were administered daily by esophageal gavage for 28 days. After sacrifice, number of lesions, lesion size, cell proliferation, vascularization and HA deposition within the endometriotic-like lesions were evaluated. In vitro, cell proliferation was assessed in endometrial epithelial cells (ECC-1) and in endometrial stromal cells (t-HESC); and migration was evaluated in t-HESC.Results: There was a significant reduction in the number of lesions developed in mice that started the 4MU treatment on day 2 compared to the control group. Also, a significant inhibition in lesion size was observed in mice that started the treatment on day 2 compared to those that started on day 15, endometriotic implants’ cell proliferation, vascularization and HA deposition remained unchanged. In vitro, both cell proliferation and cell migration were inhibited by 4MU treatment.Conclusions: The inhibition of HA synthesis could be a beneficial and alternative option to treat endometriosis. Further research is necessary to elucidate better strategies for delivering this promising drug.