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. 2013 Jul;30(7):969-74.
doi: 10.1007/s10815-013-0029-7. Epub 2013 Jun 30.

Uterine fibroids are characterized by an impaired antioxidant cellular system: potential role of hypoxia in the pathophysiology of uterine fibroids

N M Fletcher  1 , M G Saed, H M Abu-Soud, A Al-Hendy, M P Diamond, G M Saed
Affiliations

Uterine fibroids are characterized by an impaired antioxidant cellular system: potential role of hypoxia in the pathophysiology of uterine fibroids

N M Fletcher et al. J Assist Reprod Genet. 2013 Jul.

Abstract

Purpose: Fibroids are the most common smooth muscle overgrowth in women. This study determined the expression and the effect of hypoxia on two potent antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) on human fibroid cells.

Methods: Immortalized human leiomyoma (fibroid) and myometrial cells were subjected to hypoxia (2 % O2, 24 h). Total RNA and cell homogenate were obtained from control and treated cells; CAT and SOD mRNA and activity levels were determined by real-time RT-PCR and ELISA, respectively.

Results: Fibroid cells have significantly lower antioxidant enzymes, SOD and CAT mRNA and activity levels than normal myometrial cells (p < 0.05). Hypoxia treatment significantly increased SOD activity in myometrial cells while significantly decreasing CAT activity in fibroid cells (p < 0.05). There was no significant difference in CAT mRNA levels or activity in response to hypoxia in myometrial cells. Also, there was no significant difference in SOD mRNA levels in response to hypoxia in myometrial cells.

Conclusion: This is the first report to show that uterine fibroids are characterized by an impaired antioxidant cellular enzymatic system. More importantly, our results indicate a role for hypoxia in the modulation of the balance of those enzymes in fibroid and myometrial cells. Collectively, these results shed light on the pathophysiology of fibroids thereby providing potential targets for novel fibroid treatment.

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Figures

Fig. 1
Fig. 1
Normal human myometrial cells and fibroid cells were treated with and without hypoxia (2 % O2, 24 h). a Real-time RT-PCR was utilized to measure CAT mRNA levels in RNA isolated from normal myometrial and fibroid cells. b CAT activity was detected in protein obtained from normal myometrial and fibroid cells. *Indicates statistical significance as compared to untreated normal myometrial cells and **indicates statistical significance as compared to untreated fibroid cells (p < 0.05). Error bars represent standard deviation of the mean
Fig. 2
Fig. 2
Normal human myometrial cells and fibroid cells were treated with and without hypoxia (2 % O2, 24 h). a Real-time RT-PCR was utilized to measure SOD3 mRNA levels in RNA isolated from normal myometrial and fibroid cells. b SOD activity was detected in protein obtained from normal myometrial and fibroid cells. *Indicates statistical significance as compared to untreated normal myometrial cells (p < 0.05). Error bars represent standard deviation of the mean
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