Abstract

Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in-vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma-radiation (3.2 Gy, LD20), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

Highlights

  • Premature ovarian failure (POF) is a heterogeneous disorder defined as cessation of ovarian function with elevated gonadotropins and low estrogen levels before or at the age of 40 [1]

  • Animals treated with sodium selenite alone did not show any significant difference from the control group (Table 1)

  • The molecular mechanisms underlying the potential ovarian and uterine radioprotective effect of sodium selenite has been assessed by studying its effects on different markers of oxidative stress, apoptosis, proliferation and folliculogenesis in an experimental model of radiation-induced ovarian failure

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Summary

Introduction

Premature ovarian failure (POF) is a heterogeneous disorder defined as cessation of ovarian function with elevated gonadotropins and low estrogen levels before or at the age of 40 [1]. It affects approximately one in 10,000 women by age of 20; one in 1,000 women by age of 30; one in 100 women by age of 40 [2]. The increase in ROS production in granulosa cells seems to have a deleterious effect on oocyte fertilization, embryo quality and implantation rate. It seems that germ cells, in comparison with somatic cells, are more susceptible to oxidative stress [8,9]. ; radiotherapy is known to result in oocyte loss [10] and ovarian atrophy, combined with reduce follicle stores, leading subsequently to menstrual irregularities, ovarian failure and associated infertility

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