Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca²⁺ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy.

Hyperandrogenism is a key hallmark of polycystic ovary syndrome, a prevalent endocrine disorder affecting women of reproductive age and often leading to infertility. We previously observed that high doses of D‐chiro‐inositol in mice reduce ovarian aromatase expression, contributing to a hyperandrogenic state. Given that similar effects have been reported in tumour‐derived human KGN granulosa cells treated with bacterial lipopolysaccharide, we investigated whether D‐chiro‐inositol could elicit a comparable hyperandrogenic response in these cells, thereby shedding light on aberrant mechanisms potentially involved in polycystic ovary syndrome. Using lipopolysaccharide and myo‐inositol as controls, we assessed KGN cells for proliferation, viability, inflammatory response, cellular and mitochondrial reactive oxygen species, expression of antioxidant enzyme genes, aromatase expression, and estradiol secretion. None of the treatments affected cell proliferation or viability. Both D‐chiro‐inositol and myo‐inositol showed anti‐inflammatory and antioxidant effects, whereas lipopolysaccharide induced inflammation and acted as a pro‐oxidant. Notably, D‐chiro‐inositol and lipopolysaccharide downregulated aromatase gene and protein expression, resulting in reduced estradiol secretion. In contrast, myo‐inositol had no significant impact on aromatase expression or oestrogen production. These findings suggest that D‐chiro‐inositol and lipopolysaccharide may serve as useful tools for probing the dysregulated molecular and cellular pathways associated with polycystic ovary syndrome, particularly those contributing to hyperandrogenism.

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositols may influence oocyte maturation, improve intracellular Ca2⁺ oscillation in the oocytes and have been proposed as potential interventions for restoring spontaneous ovulation. MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase thus regulating androgen synthesis. Under physiological conditions, MYO/DCI ratio is maintained at 40:1 in the plasma. In women with PCOS, MYO/DCI ratio lowers to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositols may be a promising strategy to address female infertility and sustain healthy pregnancy.