P-375 Effect of D-Chiro-Inositol in a mouse model of endometriosis
Authors: Placidi M , Vergara T , Casoli G , Cocciolone D , Palmerini M G , Mascitti I A , D'Alessandro A M , Gambioli R , Tatone C , Bevilacqua A , Di Emidio G 
Published: June 2023

Study question

Can D-Chiro Inositol administration mitigate the phenotype of endometriosis in a mouse model?

Summary answer

Based on an endometriosis mouse model, we demonstrated that administration of D-Chiro Inositol can reduce development of endometriotic lesions.

What is known already

Endometriosis, a disease affecting 5-10% of women of reproductive age, is characterized by the spread of endometrial-like tissue outside the uterine cavity that produces ectopic endometriotic lesions causing pain and infertility. The sensitivity of endometriosis to estrogens is a characteristic that can be used for therapeutic purposes. D-Chiro Inositol (DCI), one of the nine isomers of Inositol, is known to decrease the CYP19A1 aromatase gene expression in granulosa cells. Based on these premises, it was suggested that treatment with DCI may have clinical application in conditions where decreased estrogen levels is required.

Study design, size, duration

To address the study question, a mouse model of endometriosis was generated. Out of 20 CD1 mice, 4 mice were randomly selected as donors of uterine fragments and the remaining 16 were recipient mice. The first day after transplantation, mice were randomly assigned to four experimental group which received for 28 days 2ml of water containing: none (CTRL); DCI 0.4mg (DCI 0.4); DCI 0.2mg and Dienogest 0.33ng (DCI 0.2+DG 0.33); DG 0.67ng (DG 0.67).

Participants/materials, setting, methods

Uterine horns were removed from donor mice at the diestrous stage of the reproductive cycle. The tissue cut into fragments was inoculated in recipient mice by intraperitoneal injection. Four weeks after induction, all mice were sacrificed. Their endometriotic lesions were excised, measured by number and size, and examined for the presence of blood vessels vascularization under stereomicroscope. Then, lesions were processed for histology examination by hematoxilin-eosin (H&E) and Azan Mallory staining.

Main results and the role of chance

Endometriotic lesions developed in recipient mice met all criteria for endometriosis, including the presence of endometrial epithelial and stromal cells, and encapsulation in neighboring tissues or organs. The lesions number was reduced in all the treatment groups when compared to control (p &lt; 0.05, t-test), and no differences were observed among DCI 0.4, DCI 0.2+DG 0.33 and DG 0.67. Concomitantly the rate of vascularized lesions was lower in the treated groups, with more pronounced effect in the DCI 0.4 group where no vascularized lesions were observed (p &lt; 0.05, t-test). The histological analysis revealed a marked reduction of endometriotic foci in all groups. These results provide evidence that DCI can reduce development and vascularization of endometriotic lesions in a mouse model, an effect that is not observed when it is employed at lower dose in association with DG. Although molecular mechanisms underlying DCI effects requires further investigation, present findings support the hypothesis that DCI could be more effective than DG in mitigating endometriosis phenotype.

Limitations, reasons for caution

Results from animal studies should be extrapolated to humans with caution.

Wider implications of the findings

Present findings may open new avenue in testing whether DCI may have clinical application in endometriosis therapy.

Trial registration number

Not Applicable