Elkafas, H., Badary, O., Elmorsy, E., Kamel, R., Yang, Q., Al-Hendy, A. (2021). Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids. Journal of Advanced Pharmacy Research, 5(2), 260-275. doi: 10.21608/aprh.2021.66748.1124
Hoda Elkafas; Osama Ahmed Badary; Engy Elmorsy; Rehab Kamel; Qiwei Yang; Ayman Al-Hendy. "Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids". Journal of Advanced Pharmacy Research, 5, 2, 2021, 260-275. doi: 10.21608/aprh.2021.66748.1124
Elkafas, H., Badary, O., Elmorsy, E., Kamel, R., Yang, Q., Al-Hendy, A. (2021). 'Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids', Journal of Advanced Pharmacy Research, 5(2), pp. 260-275. doi: 10.21608/aprh.2021.66748.1124
Elkafas, H., Badary, O., Elmorsy, E., Kamel, R., Yang, Q., Al-Hendy, A. Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids. Journal of Advanced Pharmacy Research, 2021; 5(2): 260-275. doi: 10.21608/aprh.2021.66748.1124
Endocrine-Disrupting Chemicals and Vitamin D Deficiency in the Pathogenesis of Uterine Fibroids
1Department of Pharmacology and Toxicology, Egyptian Drug Authority (EDA) formally, (NODCAR), Cairo 35521, Egypt.
2Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60612, USA
3Department of Pharmacology, Faculty of Pharmacy, British University in Egypt
4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt
5Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, 60637, USA
Abstract
Uterine fibroids (UFs) are the most prevalent gynecologic neoplasm, affecting 70–80% of women over their lifespan. Although UFs are benign, they can become life-threatening and require invasive surgeries such as myomectomy and hysterectomy. Notwithstanding the significant negative influence, UFs have on female reproductive health, very little is known about early events that initiate tumor development. Several risk factors for UFs have been identified, including vitamin D deficiency, inflammation, DNA repair deficiency, and environmental exposures to endocrine-disrupting chemicals (EDCs). EDCs have come under scrutiny recently due to their role in UF development. Epidemiologic studies have found an association between increased risk for early UF diagnosis and in utero EDC exposure. Environmental exposure to EDCs during uterine development increases UF incidence in a UF animal model. Notably, several studies demonstrated that abnormal myometrial stem cells (MMSCs) are the cell origin for UFs development. Our recent studies demonstrated that early-life EDC exposure reprogrammed the MMSCs toward a pro-fibroid landscape and altered the DNA repair and inflammation pathways. Notably, Vitamin D3 (VITD3) as a natural compound shrank the UF growth concomitantly with the reversion of several abnormal biological pathways. It ameliorated the developmental exposure-induced DNA damage and pro-inflammation pathway in primed MMSCs. This review highlights and emphasizes the importance of multiple pathway interactions in the context of hypovitaminosis D at the MMSCs level and provides proof-of-concept information that can help develop a safe, long-term, durable, and non-surgical therapeutic option for UFs.
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