Dottorato in MORFOGENESI E INGEGNERIA TISSUTALE

Titolo della tesi: RESTORE OF STEROIDOGENIC PATHWAY UPON (IN VITRO AND IN VIVO) TREATMENT WITH MYO-INS AND D-CHIRO-INS IN PCOS-INDUCED MOUSE MODEL.

Polycystic ovary syndrome (PCOS) is a common metabolic dysfunction and heterogeneous endocrine disorder in women of reproductive age. Women with PCOS develop infertility and non-reproductive metabolic abnormalities, in particular, there is decrease of production of female hormones due to a lack/reduction of Aromatase inside the ovaries. There are several approaches used to restore hormonal balance, but in recent years a lot of attention has been focused on the treatments with natural molecules, myo-Inositol and D-chiro-Inositol. Experimental studies show that a correct treatment strategy could be a combination of both isomers. However, the correct formula is still a matter of debate. We tested the action of both isomers of inositol In vitro, with primary cultures of Granulosa and Theca isolated from the ovaries of PCOS induced mice, and In vivo through treatment of PCOS mice models. Different ratios of both isomers and different dietary supplement concentrations of myo-Ins and D-chiro-Ins were tested in primary culture in order to find the correct formula to use to reverse the molecular phenotype. Through In vitro studies we found that the ratio myo-Ins:D-chiro-Ins 40:1 with concentration of myo-Ins 0.5 mM and D-chiro-Ins 12.5 μM increases the expression of key enzymes involved in steroidogenesis pathway. After that, we increased the expression of enzyme of steroidogenic pathway and female hormone level in blood through In vivo treatment of PCOS mice model with the same ratio and concentration of In vitro studies.