Combating Radiation Therapy-Induced Damage to the Ovarian Environment

Duncan, Francesca E.; Kimler, Bruce F.; Briley, Shawn M.

doi:10.2217/fon-2016-0121

Cited by 28 publications

(25 citation statements)

References 21 publications

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“…Radiotherapy is one of the most important therapies for cancer that relies on DNA damage to eradicate tumors [1]. However, this process has the unintended off-target effect of permanently damaging normal tissues that are within the treatment field [2, 3] during or shortly after the completion of irradiation and thus limiting its therapeutic outcome [4]. As the life expectancy of young cancer patients has significantly increased due to advances in cytotoxic treatments, more females of reproductive age are experiencing premature ovarian failure (POF) after radiotherapy [5], and thus, it is now considered necessary to take appropriate measures for fertility preservation in surviving cancer patients [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Mahran

Badr

Aldosari

et al. 2019

Oxidative Medicine and Cellular Longevity

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Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD20) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.

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Section: Introductionmentioning

confidence: 99%

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Mahran

Badr

Aldosari

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…In fact, we recently showed that a single dose exposure to 1 Gy TBI elicited significant germ cell damage without any overt stromal damage even up to 5 weeks post-exposure [ 44 ]. Thus, additional impacts of radiation damage that have been observed in human ovaries, such as stromal fibrosis and impaired vasculature, are late effects [ 4 , 9 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although these approaches are lifesaving, they can have unintended off target health consequences. For example, exposure to radiation can accelerate reproductive aging and entry into menopause [ 4 , 5 ]. This accelerated reproductive aging in turn can lead to subfertility, infertility, or increased complications during pregnancies that are achieved [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Use of a Small Animal Radiation Research Platform (SARRP) facilitates analysis of systemic versus targeted radiation effects in the mouse ovary

2018

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BackgroundRadiation exposure is known to cause accelerated aging and damage to the ovary, but the contribution of indirect versus direct effects is not well understood. We used the Small Animal Radiation Research Platform (SARRP) (Xstrahl) to deliver radiation to precise fields equivalent to clinical practice, allowing us to investigate systemic versus targeted damage in a structure as small as the mouse ovary. The X-ray dose was kept constant at 1 Gy, but the field varied. Mice either received total body irradiation (TBI), radiation targeted to both ovaries (T2), or radiation targeted to one ovary (left) while the contralateral ovary (right) was spared (T1). Sham mice, handled similarly to the other cohorts but not exposed to radiation, served as controls. Two weeks post-exposure, ovaries were harvested and analyzed histologically to identify and count follicles within each ovary.ResultsRadiation significantly reduced primordial follicles in the TBI and T2 cohorts compared to the Sham cohort. There were no significant differences between these two irradiated groups. These findings suggest that at 1 Gy, the extent of damage to the ovary caused by radiation is similar despite the different delivery methods. When investigating the T1 cohort, targeted ovaries showed a significant decrease in primordial and growing follicles compared to non-targeted contralateral ovaries.ConclusionsThese findings demonstrate that the SARRP is an effective strategy for delivering precise ionizing radiation to small organs such as mouse ovaries. Such tools will facilitate identifying the relative risks to ovarian function associated with different radiation fields as well as screening the efficacy of emerging fertoprotective agents.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0442-8) contains supplementary material, which is available to authorized users.

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“…Like the male reproductive system, the female reproductive system is also susceptible to radiation damage, but even more so. The human oocyte has been estimated to have an LD 50 value of <2 Gy [142]. The functional unit of the ovary is the 'follicle' and is comprised of the oocyte and its companion somatic granulosa cells: the latter dividing cells are thought to be the initial target/site of radiation damage and ultimate contributor of follicular death [142].…”

Section: 25mentioning

confidence: 99%

“…The human oocyte has been estimated to have an LD 50 value of <2 Gy [142]. The functional unit of the ovary is the 'follicle' and is comprised of the oocyte and its companion somatic granulosa cells: the latter dividing cells are thought to be the initial target/site of radiation damage and ultimate contributor of follicular death [142]. Irradiation of the ovaries leads to a reduction in the number of ova with the consequence of a dose-dependent earlier onset of the menopause.…”

Section: 25mentioning

confidence: 99%

Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

Singh

Seed²

2020

Expert Opinion on Pharmacotherapy

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Introduction: There is a limited array of currently available medicinals that are useful for either the prevention, mitigation or treatment of bodily injuries arising from ionizing radiation exposure. Area covered: In this brief article, the authors review those pharmacologic agents that either are currently being used to counter the injurious effects of radiation exposure, or those that show promise and are currently under development. Expert opinion: Although significant, but limited progress has been made in the development and fielding of safe and effective pharmacotherapeutics for select types of acute radiation-associated injuries, additional effort is needed to broaden the scope of drug development so that overall health risks associated with both short-and long-term injuries in various organ systems can be reduced and effectively managed. There are several promising radiation countermeasures that may gain regulatory approval from the government in the near future for use in clinical settings and in the aftermath of nuclear/radiological exposure contingencies. ARTICLE HISTORY

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Combating Radiation Therapy-Induced Damage to the Ovarian Environment

Cited by 28 publications

References 21 publications

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

Use of a Small Animal Radiation Research Platform (SARRP) facilitates analysis of systemic versus targeted radiation effects in the mouse ovary

Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

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