Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment

Ali, Mohamed; Shahin, Sara; Sabri, Nagwa Ali; Al-Hendy, Ayman; Yang, Qiwei

doi:10.1038/s41401-018-0184-6

Cited by 37 publications

(28 citation statements)

References 50 publications

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“…The antigen–antibody complex was detected with the Pierce enhanced chemiluminescence detection kit (Trident Femto Western HRP Substrate (GeneTex, Irvine, CA, USA). Specific protein bands were visualized using the ChemiDoc XRS+ molecular imager (Bio-Rad, Hercules, CA, USA) [ 32 , 39 ]. Quantification of each protein band’s intensity was undertaken using Bio-Rad Image Lab software and normalized against the corresponding β-actin.2.6.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously demonstrated that VitD3 has an inhibitory effect on the UF phenotype and decreases the size of the UFs [ 29 , 30 , 31 ]. It may also diminish the accumulation of DNA damage in UF tissues [ 32 ]. Earlier studies have demonstrated that low serum levels of VitD3 and downregulated vitamin D receptor expression have been observed with UFs, with increases in DNA damage and decreases in DNA repair factors, including the double-strand break (DSB) sensors, the MRN complex, mediators, and effectors in UF cells [ 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D3 Ameliorates DNA Damage Caused by Developmental Exposure to Endocrine Disruptors in the Uterine Myometrial Stem Cells of Eker Rats

Elkafas

Ali

Elmorsy

et al. 2020

Cells

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Early-life exposure of the myometrium to endocrine-disrupting chemicals (EDCs) has been shown to increase the risk of uterine fibroid (UF) prevalence in adulthood. Vitamin D3 (VitD3) is an unique, natural compound that may reduce the risk of developing UFs. However, little is known about the role and molecular mechanism of VitD3 on exposed myometrial stem cells (MMSCs). We investigated the role and molecular mechanism underlying VitD3 action on DNA damage response (DDR) defects in rat MMSCs due to developmental exposure to diethylstilbestrol (DES), with the additional goal of understanding how VitD3 decreases the incidence of UFs later in life. Female newborn Eker rats were exposed to DES or a vehicle early in life; they were then sacrificed at 5 months of age (pro-fibroid stage) and subjected to myometrial Stro1+/CD44+ stem cell isolation. Several techniques were performed to determine the effect of VitD3 treatment on the DNA repair pathway in DES-exposed MMSCs (DES-MMSCs). Results showed that there was a significantly reduced expression of RAD50 and MRE11, key DNA repair proteins in DES-exposed myometrial tissues, compared to vehicle (VEH)-exposed tissues (p < 0.01). VitD3 treatment significantly decreased the DNA damage levels in DES-MMSCs. Concomitantly, the levels of key DNA damage repair members, including the MRN complex, increased in DES-MMSCs following treatment with VitD3 (p < 0.01). VitD3 acts on DNA repair via the MRN complex/ATM axis, restores the DNA repair signaling network, and enhances DDR. This study demonstrates, for the first time, that VitD3 treatment attenuated the DNA damage load in MMSCs exposed to DES and classic DNA damage inducers. Moreover, VitD3 targets primed MMSCs, suggesting a novel therapeutic approach for the prevention of UF development.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin D3 Ameliorates DNA Damage Caused by Developmental Exposure to Endocrine Disruptors in the Uterine Myometrial Stem Cells of Eker Rats

Elkafas

Ali

Elmorsy

et al. 2020

Cells

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“…In 2018, further research proved that vitamin D deficiency could enhance DNA damage in the myometrium toward the UF phenotype [128]. An interesting study by Ali et al (2019) also showed that vitamin D suppressed UFs through targeting different networks in DNA repair [129]. The latest research concerning UFs and vitamin D has focused on the role of vitamin D in the Wnt/β-catenin-dependent pathway.…”

Section: Vitamin D and Uterine Fibroidsmentioning

confidence: 99%

Vitamins and Uterine Fibroids: Current Data on Pathophysiology and Possible Clinical Relevance

Ciebiera

Ali

Zgliczyńska

et al. 2020

IJMS

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Uterine fibroid (UF) is the most common benign tumor pathology of the female reproductive organs. UFs constitute the main reason for a hysterectomy and hospitalization due to gynecological conditions. UFs consist of uterine smooth muscle immersed in a large amount of extracellular matrix (ECM). Genetic studies have demonstrated that UFs are monoclonal tumors originating from the myometrial stem cells that have underwent specific molecular changes to tumor initiating stem cells which proliferate and differentiate later under the influence of steroid hormones. There is growing interest in the role of micronutrients, for example, vitamins, in UFs. This article is a comprehensive review of publications regarding the available data concerning the role of vitamins in the biology and management of UFs. In summary, the results showed that some vitamins are important in the biology and pathophysiology of UFs. For example, vitamins A and D deserve particular attention following studies of their influence on the treatment of UF tumors. Vitamins B3, C, and E have not been as widely studied as the abovementioned vitamins. However, more research could reveal their potential role in UF biology.

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“…Our data suggests that VD treatment may limit cell growth and/or division via maintaining cell cycle arrest. In addition, studies have previously demonstrated VD-enhanced DNA damage repair in uterine fibromas [43] and Ras oncogene-induced senescent fibroblasts [44]. Lending further support to linking VD to associated with induction of BRCA1 gene expression via VDR in breast and prostate cancer cells [46].…”

Section: Discussionmentioning

confidence: 69%

Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers

et al. 2020

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Hypovitaminosis D exacerbates the DNA damage load in human uterine fibroids, which is ameliorated by vitamin D3 treatment

Cited by 37 publications

References 50 publications

Vitamin D3 Ameliorates DNA Damage Caused by Developmental Exposure to Endocrine Disruptors in the Uterine Myometrial Stem Cells of Eker Rats

Vitamin D3 Ameliorates DNA Damage Caused by Developmental Exposure to Endocrine Disruptors in the Uterine Myometrial Stem Cells of Eker Rats

Vitamins and Uterine Fibroids: Current Data on Pathophysiology and Possible Clinical Relevance

Association between vitamin D and ovarian cancer development in BRCA1 mutation carriers

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