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nutrientsReviewVitamin D: Mechanism of Action and Biological Effects in Uterine FibroidsDaniele Vergara 1, , William H. Catherino two,3 , Giuseppe Trojano four and Andrea Tinelli five,6,Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, strada Prov. le Lecce-Monteroni, 73100 Lecce, Italy Division of Obstetrics and Gynecology, Uniformed Services University on the Health Sciences, Bethesda, MD 20814, USA; [email protected] Plan in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Youngster Well being and Human Improvement, National Institutes of Health, Bethesda, MD 20814, USA Department of Obstetrics and Gynecology, “Madonna delle Grazie” Hospital, 75100 Matera, Italy; [email protected] Department of Obstetrics and Gynecology, “Veris delli Ponti” Hospital, Scorrano, 73020 Lecce, Italy; [email protected] Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Vito Fazzi Hospital, 73100 Lecce, Italy Laboratory of Human Physiology, Phystech BioMed College, Faculty of Biological Medical Physics, Moscow Institute of Physics and Technology (State University), MDM2 Inhibitor Biological Activity Dolgoprudny, 141701 Moscow, Russia Correspondence: [email protected]: Vergara, D.; Catherino, W.H.; Trojano, G.; Tinelli, A. Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids. Nutrients 2021, 13, 597. https:// doi.org/10.3390/nu13020597 Academic Editors: Giovanni Passeri and Sandro Giannini Received: 24 January 2021 Accepted: eight February 2021 Published: 11 FebruaryAbstract: Uterine fibroids (UFs) would be the most typical benign gynecological tumors. It was estimated that fifty percent of ladies presenting with UFs has symptomatology that negatively influences their top quality of life. Pharmacological and/or surgical remedies are often required, depending on the woman’s wish to preserve fertility, having a high influence on healthcare fees. Frequently, the usage of presently accessible pharmacological treatments might result in unwanted effects. Therefore, there is a developing interest in a natural and secure approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in individuals with UFs raised interest in the prospective biological effects of vitamin D supplementation. In vitro research proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of a variety of biological processes, such as proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in portion the advantageous effects of vitamin D supplementation in decreasing UFs growth and tumor volume. Randomized controlled trials and large population research are mandatory because the prospective clinical rewards are probably to be substantial. Keyword phrases: uterine fibroids; leiomyoma; vitamin D; vitamin D receptor (VDR); cell signalingPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.1. Introduction Uterine fibroids (UFs), also known as uterine leiomyomas or myomas, would be the most frequent benign tumors in ladies of reproductive age. Much more precisely, UFs are monoclonal tumors derived from smooth muscle tissue, the PDE3 Modulator Gene ID myometrium [1]. UFs incidence ranges between 30 and 70 in ladies of reproductive age, increases at the finish on the reproductive age and is larger in some ethnic gro.