{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:10:11Z","timestamp":1793124611001,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University","award":["RG123188AEFD2C0D"],"award-info":[{"award-number":["RG123188AEFD2C0D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs.<\/jats:p>","DOI":"10.3390\/cells13141171","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T15:27:20Z","timestamp":1720538840000},"page":"1171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inositol Restores Appropriate Steroidogenesis in PCOS Ovaries Both In Vitro and In Vivo Experimental Mouse Models"],"prefix":"10.3390","volume":"13","author":[{"given":"Valeria","family":"Fedeli","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University La Sapienza, 00185 Rome, Italy"},{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"},{"name":"The Experts Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1805-3181","authenticated-orcid":false,"given":"Vittorio","family":"Unfer","sequence":"additional","affiliation":[{"name":"The Experts Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), 00161 Rome, Italy"},{"name":"Dept. of Gynaecology, UniCamillus\u2014Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Dinicola","sequence":"additional","affiliation":[{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"},{"name":"The Experts Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1543-2802","authenticated-orcid":false,"given":"Antonio Simone","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Unit of Obstetrics and Gynecology, \u201cPaolo Giaccone\u201d Hospital, Department of Health Promotion, Mother and ChildCare, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Canipari","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Unit of Histology and Medical Embryology, Sapienza, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7512-7984","authenticated-orcid":false,"given":"Noemi","family":"Monti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University La Sapienza, 00185 Rome, Italy"},{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Querqui","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University La Sapienza, 00185 Rome, Italy"},{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3447-6160","authenticated-orcid":false,"given":"Emanuele","family":"Galante","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University La Sapienza, 00185 Rome, Italy"},{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Laurenzi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Unit of Histology and Medical Embryology, Sapienza, University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0408-4136","authenticated-orcid":false,"given":"Mariano","family":"Bizzarri","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University La Sapienza, 00185 Rome, Italy"},{"name":"Systems Biology Group Lab, University La Sapienza, 00185 Rome, Italy"},{"name":"The Experts Group on Inositol in Basic and Clinical Research, and on PCOS (EGOI-PCOS), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Singh, S., Pal, N., Shubham, S., Sarma, D.K., Verma, V., Marotta, F., and Kumar, M. (2023). Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. J. Clin. Med., 12.","DOI":"10.3390\/jcm12041454"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"The Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group (2004). Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril., 81, 19\u201325.","DOI":"10.1016\/j.fertnstert.2003.10.004"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13048-022-01091-0","article-title":"Insulin resistance in polycystic ovary syndrome across various tissues: An updated review of pathogenesis, evaluation, and treatment","volume":"16","author":"Zhao","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chen, W., and Pang, Y. (2021). Metabolic Syndrome and PCOS: Pathogenesis and the Role of Metabolites. Metabolites, 11.","DOI":"10.3390\/metabo11120869"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.bpobgyn.2016.03.009","article-title":"Diagnostic criteria for PCOS: Is there a need for a rethink?","volume":"37","author":"Dewailly","year":"2016","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sun, Y., Gao, S., Ye, C., and Zhao, W. (2023). Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications. Front. Cell Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1142041"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2147\/TACG.S200341","article-title":"Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives","volume":"12","author":"Khan","year":"2019","journal-title":"Appl. Clin. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.mce.2010.08.002","article-title":"The role of low-grade inflammation in the polycystic ovary syndrome","volume":"335","author":"Repaci","year":"2011","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.tem.2023.08.005","article-title":"Questioning PCOS phenotypes for reclassification and tailored therapy","volume":"34","author":"Myers","year":"2023","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1210\/er.16.3.322","article-title":"Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion","volume":"16","author":"Ehrmann","year":"1995","journal-title":"Endocr. Rev."},{"key":"ref_11","unstructured":"Jameson, J.L., and De Groot, L.J. (2016). Ovarian hormone synthesis. Endocrinology: Adult and Pediatric, Saunders\/Elsevier. [7th ed.]."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1210\/mend.13.6.0311","article-title":"Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries","volume":"13","author":"Nelson","year":"1999","journal-title":"Mol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.steroids.2011.10.013","article-title":"Tissue physiology and pathology of aromatase","volume":"77","author":"Stocco","year":"2012","journal-title":"Steroids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1136\/bmj.1.5241.1724","article-title":"Defective Biosynthesis of Ovarian Steroids in the Stein-Leventhal Syndrome","volume":"1","author":"Short","year":"1961","journal-title":"Br. Med. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1210\/jcem-49-4-514","article-title":"Functional studies of aromatase activity in human granulosa cells from normal and polycystic ovaries","volume":"49","author":"Erickson","year":"1979","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","unstructured":"Serio, M. (1976). Functional aberrations of the hypothalamic-pituitary system in polycystic ovary syndrome: A consideration of the pathogenesis. The Endocrine Function of Human Ovary, Academic Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0039-128X(96)00181-X","article-title":"Expression of aromatase in the ovary: Down-regulation of mRNA by the ovulatory luteinizing hormone surge","volume":"62","author":"Fitzpatrick","year":"1997","journal-title":"Steroids"},{"key":"ref_18","first-page":"1739","article-title":"Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: Impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood","volume":"82","author":"Mullis","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1038\/s41598-023-28260-5","article-title":"Effects of time-restricted feeding on letrozole-induced mouse model of polycystic ovary syndrome","volume":"13","author":"Ryu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e923073","DOI":"10.12659\/MSM.923073","article-title":"Letrozole Rat Model Mimics Human Polycystic Ovarian Syndrome and Changes in Insulin Signal Pathways","volume":"26","author":"Xu","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dinicola, S., Unfer, V., Facchinetti, F., Soulage, C.O., Greene, N.D., Bizzarri, M., Lagana, A.S., Chan, S.Y., Bevilacqua, A., and Pkhaladze, L. (2021). Inositols: From Established Knowledge to Novel Approaches. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910575"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Unfer, V., Russo, M., Aragona, C., Bilotta, G., Montanino Oliva, M., and Bizzarri, M. (2023). Treatment with Myo-Inositol Does Not Improve the Clinical Features in All PCOS Phenotypes. Biomedicines, 11.","DOI":"10.3390\/biomedicines11061759"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bizzarri, M., Monti, N., Piombarolo, A., Angeloni, A., and Verna, R. (2023). Myo-Inositol and D-Chiro-Inositol as Modulators of Ovary Steroidogenesis: A Narrative Review. Nutrients, 15.","DOI":"10.3390\/nu15081875"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1080\/09513590903015544","article-title":"Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome","volume":"25","author":"Zacche","year":"2009","journal-title":"Gynecol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1473612","DOI":"10.1155\/2016\/1473612","article-title":"Myo-Inositol in the Treatment of Teenagers Affected by PCOS","volume":"2016","author":"Pkhaladze","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.lfs.2017.10.020","article-title":"Hormone-induced rat model of polycystic ovary syndrome: A systematic review","volume":"191","author":"Noroozzadeh","year":"2017","journal-title":"Life Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0015-0282(16)41297-5","article-title":"Dehydroepiandrosterone-induced polycystic ovaries and acyclicity in the rat","volume":"26","author":"Knudsen","year":"1975","journal-title":"Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.111.097808","article-title":"Rodent models for human polycystic ovary syndrome","volume":"86","author":"Walters","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1590\/S1413-95962004000600006","article-title":"Polycystic ovarian syndrome: Temporal characterization of the induction and reversion process in an experimental model","volume":"41","author":"Salvetti","year":"2004","journal-title":"Braz. J. Vet. Res. Anim. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kang, X., Jia, L., and Shen, X. (2015). Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/943694"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chu, W., Zhai, J., Xu, J., Li, S., Li, W., Chen, Z.J., and Du, Y. (2019). Continuous Light-Induced PCOS-Like Changes in Reproduction, Metabolism, and Gut Microbiota in Sprague-Dawley Rats. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.03145"},{"key":"ref_32","first-page":"86","article-title":"A Challenging Task\u2014How to Successfully Separate Theca and Granulosa Cells: A Mandatory Step for Investigating Ovary Steroidogenesis","volume":"4","author":"Fedeli","year":"2020","journal-title":"Org. J. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1080\/17425255.2019.1651839","article-title":"Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors","volume":"15","author":"Garzon","year":"2019","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000228720","article-title":"Identification of suitable normalizing genes for quantitative real-time RT-PCR analysis of gene expression in fetal mouse gonads","volume":"3","author":"Svingen","year":"2009","journal-title":"Sex. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/0002-9378(69)90510-9","article-title":"Induction of polycystic ovarian disease in rats by continuous light. I. The reproductive cycle, organ weights, and histology of the ovaries","volume":"103","author":"Singh","year":"1969","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nrendo.2017.57","article-title":"PCOS: Animal models for PCOS\u2014Not the real thing","volume":"13","author":"Azziz","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.fertnstert.2005.06.013","article-title":"Persistent estrus rat models of polycystic ovary disease: An update","volume":"84","author":"Singh","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9387","DOI":"10.1002\/jcp.27623","article-title":"Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model","volume":"234","author":"Bevilacqua","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0303-7207(00)00425-1","article-title":"Type 5 17beta-hydroxysteroid dehydrogenase: Its role in the formation of androgens in women","volume":"171","author":"Dufort","year":"2001","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1210\/jcem-49-5-687","article-title":"The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro","volume":"49","author":"McNatty","year":"1979","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/1071-5576(94)00061-5","article-title":"The effects of insulin on 3 beta-hydroxysteroid dehydrogenase expression in human luteinized granulosa cells","volume":"2","author":"McGee","year":"1995","journal-title":"J. Soc. Gynecol. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/0005-2760(83)90108-X","article-title":"Free and total lipid myo-inositol concentrations decrease with age in human brain","volume":"753","author":"Stokes","year":"1983","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1210\/en.2016-1252","article-title":"The Hydroxysteroid (17beta) Dehydrogenase Family Gene HSD17B12 Is Involved in the Prostaglandin Synthesis Pathway, the Ovarian Function, and Regulation of Fertility","volume":"157","author":"Kemilainen","year":"2016","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.reprotox.2022.04.010","article-title":"DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges","volume":"111","author":"Liu","year":"2022","journal-title":"Reprod. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/humupd\/dmab004","article-title":"Adipocyte and steroidogenic cell cross-talk in polycystic ovary syndrome","volume":"27","author":"Rodgers","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1177\/1933719113518985","article-title":"Hyperinsulinemia Alters Myoinositol to d-chiroinositol Ratio in the Follicular Fluid of Patients With PCOS","volume":"21","author":"Unfer","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Monastra, G., Vucenik, I., Harrath, A.H., Alwasel, S.H., Kamenov, Z.A., Lagana, A.S., Monti, N., Fedeli, V., and Bizzarri, M. (2021). PCOS and Inositols: Controversial Results and Necessary Clarifications. Basic Differences Between D-Chiro and Myo-Inositol. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.660381"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12978-021-01073-3","article-title":"Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies","volume":"18","author":"Merviel","year":"2021","journal-title":"Reprod. Health"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Sacchi, S., Marinaro, F., Tondelli, D., Lui, J., Xella, S., Marsella, T., Tagliasacchi, D., Argento, C., Tirelli, A., and Giulini, S. (2016). Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol. Reprod. Biol. Endocrinol., 14.","DOI":"10.1186\/s12958-016-0189-2"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bevilacqua, A., Dragotto, J., Lucarelli, M., Di Emidio, G., Monastra, G., and Tatone, C. (2021). High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115691"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Chu, W., Li, S., Geng, X., Wang, D., Zhai, J., Lu, G., Chan, W.Y., Chen, Z.J., and Du, Y. (2022). Long-term environmental exposure of darkness induces hyperandrogenism in PCOS via melatonin receptor 1A and aromatase reduction. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.954186"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1677\/joe.1.05762","article-title":"Androgen generation in adipose tissue in women with simple obesity--a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5","volume":"183","author":"Quinkler","year":"2004","journal-title":"J. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1530\/EC-17-0243","article-title":"Myo-inositol effects in women with PCOS: A meta-analysis of randomized controlled trials","volume":"6","author":"Unfer","year":"2017","journal-title":"Endocr. Connect."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/09513590.2019.1576620","article-title":"Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: A randomized controlled trial","volume":"35","author":"Mendoza","year":"2019","journal-title":"Gynecol. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Greff, D., Juhasz, A.E., Vancsa, S., Varadi, A., Sipos, Z., Szinte, J., Park, S., Hegyi, P., Nyirady, P., and Acs, N. (2023). Inositol is an effective and safe treatment in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials. Reprod. Biol. Endocrinol., 21.","DOI":"10.1186\/s12958-023-01055-z"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1080\/09513590701672405","article-title":"Myo-inositol in patients with polycystic ovary syndrome: A novel method for ovulation induction","volume":"23","author":"Papaleo","year":"2007","journal-title":"Gynecol. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/17425255.2024.2306851","article-title":"Inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: Now and the future","volume":"20","author":"Lagana","year":"2024","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000536163","article-title":"The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria","volume":"89","author":"Pustotina","year":"2024","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2301554","DOI":"10.1080\/09513590.2023.2301554","article-title":"Update on the combination of myo-inositol\/d-chiro-inositol for the treatment of polycystic ovary syndrome","volume":"40","author":"Lete","year":"2024","journal-title":"Gynecol. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1056\/NEJM199904293401703","article-title":"Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome","volume":"340","author":"Nestler","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.metabol.2008.05.008","article-title":"Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome","volume":"57","author":"Cheang","year":"2008","journal-title":"Metabolism"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1507\/endocrj.EJ13-0423","article-title":"Decreased myo-inositol to chiro-inositol (M\/C) ratios and increased M\/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls","volume":"61","author":"Heimark","year":"2014","journal-title":"Endocr. J."},{"key":"ref_63","first-page":"2001","article-title":"Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system","volume":"83","author":"Nestler","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fedeli, V., Catizone, A., Querqui, A., Unfer, V., and Bizzarri, M. (2023). The Role of Inositols in the Hyperandrogenic Phenotypes of PCOS: A Re-Reading of Larner\u2019s Results. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076296"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12610-021-00131-x","article-title":"D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: A pilot study","volume":"31","author":"Monastra","year":"2021","journal-title":"Basic. Clin. Androl."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:12:22Z","timestamp":1760109142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/14\/1171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,9]]},"references-count":65,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["cells13141171"],"URL":"https:\/\/doi.org\/10.3390\/cells13141171","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,9]]}}}