High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries |
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Authors: | Arturo Bevilacqua Jessica Dragotto Micaela Lucarelli Giovanna Di Emidio Giovanni Monastra Carla Tatone |
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Affiliation: | 1.Department of Dynamic, Clinical Psychology and Health, Sapienza University of Rome, 00185 Rome, Italy;2.Systems Biology Group Lab., The Experts Group on Inositols in Basic and Clinical Research (EGOI), 00185 Rome, Italy;3.Department of Neuroscience, European Brain Research Institute (EBRI), Rome 00185, Italy; (J.D.); (M.L.);4.Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (G.D.E.); (C.T.) |
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Abstract: | Administration of 1000–1500 mg/day D-Chiro-Inositol (DCIns) or a combination of Myo-Inositol (MyoIns) and DCIns in their plasma molar ratio (40:1) for three or more months are among recommended treatments for metabolic syndrome and/or Polycystic Ovary Syndrome (PCOS). We previously confirmed the efficacy of this formulation (8.2 mg/day MyoIns and 0.2 mg/day DCIns for 10 days) in a mouse PCOS model, but also observed negative effects on ovarian histology and function of formulations containing 0.4–1.6 mg/day DCIns. We therefore analyzed effects of higher doses of DCIns, 5, 10 and 20 mg/day, administered to young adult female mice for 21 days, on ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. Five mg/day DCIns (human correspondence: 1200 mg/day) altered ovarian histology, increased serum testosterone levels and reduced the amount of aromatase of negative controls, suggesting the induction of an androgenic PCOS model. In contrast, 10–20 mg/day DCIns (human correspondence: 2400–4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles. |
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Keywords: | inositol letrozole mouse ovary PCOS model aromatase testosterone androgenic phenotype menopause |
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