Sphingosine 1-phosphate protects against radiation-induced ovarian injury in female rats—impact on mitochondrial-related genes

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.

Roles of follicle stimulating hormone and sphingosine 1-phosphate co-administered in the process in mouse ovarian vitrification and transplantation

“…S1P has been shown to inhibit granulosa cell apoptosis in ovaries and promote ovarian autoangiogenesis [ 19 ]. Furthermore, exogenous administration of S1P was shown to protect the ovarian follicle reserve by decreasing apoptosis during chemoradiotherapy [ 20 – 23 ], improve the survival rate of cryopreserved ovaries, increase the vascular density in ovarian grafts, and promote angiogenesis of the transplanted ovaries [ 24 , 25 ]. Nevertheless, S1P has a short half-life and cannot maintain long-term effects in vitro culture [ 26 ].…”

Analysis on the desert adaptability of indigenous sheep in the southern edge of Taklimakan Desert

“…The third shared gene is UQCRH, which is responsible for the electron transfer between cytochrome C and cytochrome C1, representing a part of the most critical step in the electron transfer cascade and being involved in the oxidative phosphorylation of mitochondria. In addition, UQCRH can protect the ovaries of animals from radiation-caused damage 67 .…”

“…Indigenous sheep use these genes to increase the reproductive rate and achieve multiple birth rates, directly or indirectly and in different ways, which is necessary for the continuation of the population in harsh environments. F13A1 improves heat stress tolerance of ewes 68 , while UQCRH protects the organisms from radiation-induced ovarian damage 67 , which is essential for sheep living in desert environments. As for CCDC178 and CNGA1, they are involved in immune repair 77 , 78 , while GLIS3 71 – 73 and GNAQ 76 are involved in stable fetal organ development.…”

Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases

“…Numerous investigators have demonstrated that aberrations related to sphingolipids are the culprit of insulin resistance and mitochondrial dysfunction in T2DM. 149,150 Plasma S1P concentration is reportedly low in T2DM 151 and in diabetic complications, such as cardiovascular autonomic neuropathy, 152 obesity, 153 and vascular dysfunction. 153 Moreover, the mechanisms of S1P axis action and insulin signal transduction in hepatocytes, skeletal muscle cells, adipocytes, and pancreatic β-cells have been extensively discussed.…”

“…Indeed, the development of T2DM is often associated with intracellular lipid dysregulation. Numerous investigators have demonstrated that aberrations related to sphingolipids are the culprit of insulin resistance and mitochondrial dysfunction in T2DM 149,150 . Plasma S1P concentration is reportedly low in T2DM 151 and in diabetic complications, such as cardiovascular autonomic neuropathy, 152 obesity, 153 and vascular dysfunction 153 .…”