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Abstract
The toxic effects of ionizing radiation on the gonads have been widely recognized. Sphingosine 1-phosphate (S1P) has a protective effect on ovarian injury, and although it is known that mitochondria are involved in this process, the specific mechanism is not fully understood. The present study analysed the changes in the serum AMH and ovarian histology in Sprague-Dawley female rats exposed to X-ray radiation only or co-administered with S1P. The mRNA expression profile of ovarian tissue was further analysed via next-generation sequencing and bioinformatics approaches to screen out candidate mitochondria-related genes. Finally, differentially expressed target genes were verified by real-time PCR. The results showed that ionizing radiation could reduce the serum AMH level, destroy ovarian structure and decrease the number of follicles in rats, while S1P administration significantly attenuated the impairment of ovarian function. Gene ontology (GO) and KEGG pathway analysis revealed that a variety of genes related to mitochondrial function were differentially expressed, and the protective effect of S1P on mitochondria was more obvious in the acute phase 24 h after radiation. The differentially expressed mitochondrial function-related genes associated with the protective effect of S1P were UQCRH, MICU2 and GPX4, which were subsequently verified by RT-PCR. Therefore, ionizing radiation has a significant effect on ovarian function, and S1P has a protective effect on radiation-induced ovarian injury, in which mitochondria may play an important role. This study sheds new light on the mechanism of radiation-induced ovarian injury and helps develop a novel potential strategy to control it.
Highlights
Ionizing radiation refers to the radiation that carries enough energy to make the electrons in atoms or molecules become unbound from their orbit and produce an ionization effect
The administration of Sphingosine 1-phosphate (S1P) prevented a decrease in Anti-Müllerian hormone (AMH) levels when compared to the radiation groups
This study showed that the protective effect of S1P on mitochondria was more significant 24 h after radiation, which we speculated might be related to the generation of mitochondrial dysfunction and the time of reactive oxygen species (ROS) production after radiation
Summary
Ionizing radiation refers to the radiation that carries enough energy to make the electrons in atoms or molecules become unbound from their orbit and produce an ionization effect. Zhao et al Reproductive Biology and Endocrinology (2020) 18:99 are highly sensitive to ionizing radiation. Radiation has a profound effect on ovarian function; this effect is characterized by follicular atrophy and reduced follicular storage. This can accelerate the natural decline in the number of follicles, leading to impaired ovarian hormone secretion, uterine dysfunction due to insufficient oestrogen exposure, early menopause and infertility. Mitochondria play an important role in radiationinduced cellular responses and may participate in the process of radiation damage, but the specific role and mechanism still need to be fully elucidated [5]
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