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Inositols: From Established Knowledge to Novel Approaches

Systems Biology Group Lab, 00161 Rome, Italy
Obstetrics and Gynecology Unit, Mother-Infant and Adult Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41121 Modena, Italy
CarMeN Lab, INSA-Lyon, INSERM U1060, INRA, University Claude Bernard Lyon 1, 69100 Villeurbanne, France
Newlife Birth Defects Research Centre and Developmental Biology and Cancer Programme, Institute of Child Health, University College London, London WC1E 6BT, UK
Department of Experimental Medicine, University La Sapienza, 00161 Rome, Italy
Department of Obstetrics and Gynecology, Hospital “Filippo Del Ponte”, University of Insubria, 21100 Varese, Italy
Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Department of Dynamic, Clinical Psychology and Health Studies, Sapienza University, 00161 Rome, Italy
Zhordania and Khomasuridze Institute of Reproductology, Tbilisi 0112, Georgia
Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
National Center for Drug Research and Evaluation, Italian National Institute of Health, 00161 Rome, Italy
U.O. Endocrinology in Livorno Hospital, USL Nordovest Toscana, 57100 Livorno, Italy
Oncological Endocrinology Unit, Regina Elena National Cancer Institute, IRCCS, 00161 Rome, Italy
Institute for Interpersonal Cognitive Therapy, 00100 Rome, Italy
Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
IVF Centre, Hong Kong 999077, China
Department of Human Pathology, University of Messina, 98122 Messina, Italy
Faculty of Medicine, University of Lille, 59000 Lille, France
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino, 04100 Latina, Italy
Department of Endocrinology and Diabetes, HYGEIA Hospital, Marousi, 15123 Athens, Greece
Human Reproduction Department, Hospital Juárez de México, Universidad Nacional Autónoma de México (UNAM), Mexico City 07760, Mexico
Department of Obstetrics and Gynecology Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel
Department of Internal Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria
Department of Obstetrics and Gynecology, Santo Spirito Hospital, 00193 Rome, Italy
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA
A.S.L. RMF, 00053 Civitavecchia, Italy
Department of Obstetrics and Gynecology, Near East University Hospital, Nicosia 99138, Cyprus
Women’s Health Centre, USL UMBRIA 2, 05100 Terni, Italy
IAKENTRO, Infertility Treatment Center, 54250 Thessaloniki, Greece
Reproductive Endocrinology and Infertility, South Florida Institute for Reproductive Medicine (IVFMD), Boca Raton, FL 33458, USA
Instituto de Biología y Medicina Experimental (IBYME, CONICET-FIBYME), Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET), Buenos Aires 2490, Argentina
Department of Medical & Research Technology and Pathology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
Diagnostic Techniques Unit, Medical University of Lublin, 20-081 Lublin, Poland
Author to whom correspondence should be addressed.
All authors are members of The Experts Group on Inositol in Basic and Clinical Research (EGOI).
Academic Editors: Saad Amer and Raheela N. Khan
Int. J. Mol. Sci. 2021, 22(19), 10575;
Received: 23 July 2021 / Revised: 13 September 2021 / Accepted: 22 September 2021 / Published: 30 September 2021
(This article belongs to the Special Issue Polycystic Ovary Syndrome: From Molecular Mechanisms to Therapies 2.0)
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects. View Full-Text
Keywords: myo-Inositol; D-chiro-Inositol; epimerase; FSH; PCOS; steroidogenesis; aromatase; testosterone; GDM; neural tube defects myo-Inositol; D-chiro-Inositol; epimerase; FSH; PCOS; steroidogenesis; aromatase; testosterone; GDM; neural tube defects
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MDPI and ACS Style

Dinicola, S.; Unfer, V.; Facchinetti, F.; Soulage, C.O.; Greene, N.D.; Bizzarri, M.; Laganà, A.S.; Chan, S.-Y.; Bevilacqua, A.; Pkhaladze, L.; Benvenga, S.; Stringaro, A.; Barbaro, D.; Appetecchia, M.; Aragona, C.; Bezerra Espinola, M.S.; Cantelmi, T.; Cavalli, P.; Chiu, T.T.; Copp, A.J.; D’Anna, R.; Dewailly, D.; Di Lorenzo, C.; Diamanti-Kandarakis, E.; Hernández Marín, I.; Hod, M.; Kamenov, Z.; Kandaraki, E.; Monastra, G.; Montanino Oliva, M.; Nestler, J.E.; Nordio, M.; Ozay, A.C.; Papalou, O.; Porcaro, G.; Prapas, N.; Roseff, S.; Vazquez-Levin, M.; Vucenik, I.; Wdowiak, A. Inositols: From Established Knowledge to Novel Approaches. Int. J. Mol. Sci. 2021, 22, 10575.

AMA Style

Dinicola S, Unfer V, Facchinetti F, Soulage CO, Greene ND, Bizzarri M, Laganà AS, Chan S-Y, Bevilacqua A, Pkhaladze L, Benvenga S, Stringaro A, Barbaro D, Appetecchia M, Aragona C, Bezerra Espinola MS, Cantelmi T, Cavalli P, Chiu TT, Copp AJ, D’Anna R, Dewailly D, Di Lorenzo C, Diamanti-Kandarakis E, Hernández Marín I, Hod M, Kamenov Z, Kandaraki E, Monastra G, Montanino Oliva M, Nestler JE, Nordio M, Ozay AC, Papalou O, Porcaro G, Prapas N, Roseff S, Vazquez-Levin M, Vucenik I, Wdowiak A. Inositols: From Established Knowledge to Novel Approaches. International Journal of Molecular Sciences. 2021; 22(19):10575.

Chicago/Turabian Style

Dinicola, Simona, Vittorio Unfer, Fabio Facchinetti, Christophe O. Soulage, Nicholas D. Greene, Mariano Bizzarri, Antonio S. Laganà, Shiao-Yng Chan, Arturo Bevilacqua, Lali Pkhaladze, Salvatore Benvenga, Annarita Stringaro, Daniele Barbaro, Marialuisa Appetecchia, Cesare Aragona, Maria S. Bezerra Espinola, Tonino Cantelmi, Pietro Cavalli, Tony T. Chiu, Andrew J. Copp, Rosario D’Anna, Didier Dewailly, Cherubino Di Lorenzo, Evanthia Diamanti-Kandarakis, Imelda Hernández Marín, Moshe Hod, Zdravko Kamenov, Eleni Kandaraki, Giovanni Monastra, Mario Montanino Oliva, John E. Nestler, Maurizio Nordio, Ali C. Ozay, Olga Papalou, Giuseppina Porcaro, Nikos Prapas, Scott Roseff, Monica Vazquez-Levin, Ivana Vucenik, and Artur Wdowiak. 2021. "Inositols: From Established Knowledge to Novel Approaches" International Journal of Molecular Sciences 22, no. 19: 10575.

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