Characterization of Glutathione Peroxidase 4 in Rat Oocytes, Preimplantation Embryos, and Selected Maternal Tissues during Early Development and Implantation

Abstract

This study aimed to describe glutathione peroxidase 4 (GPx4) in rat oocytes, preimplantation embryos, and female genital organs. After copulation, Sprague Dawley female rats were euthanized with anesthetic on the first (D1), third (D3), and fifth days of pregnancy (D5). Ovaries, oviducts, and uterine horns were removed, and oocytes and preimplantation embryos were obtained. Immunohistochemical, immunofluorescent, and Western blot methods were employed. Using immunofluorescence, we detected GPx4 in both the oocytes and preimplantation embryos. Whereas in the oocytes, GPx4 was homogeneously diffused, in the blastomeres, granules were formed, and in the blastocysts, even clusters were present mainly around the cell nuclei. Employing immunohistochemistry, we detected GPx4 inside the ovary in the corpus luteum, stroma, follicles, and blood vessels. In the oviduct, the enzyme was present in the epithelium, stroma, blood vessels, and smooth muscles. In the uterus, GPx4 was found in the endometrium, myometrium, blood vessels, and stroma. Moreover, we observed GPx4 positive granules in the uterine gland epithelium on D1 and D3 and cytoplasm of fibroblasts forming in the decidua on D5. Western blot showed the highest GPx4 levels in the uterus and the lowest levels in the ovary. Our results show that the GPx4 is necessary as early as in the preimplantation development of a new individual because we detected it in an unfertilized oocyte in a blastocyst and not only after implantation, as was previously thought.

Liver protection from acetaminophen hepatotoxicity using copper(I)-nicotinic acid complex

“…Oxygen radicals bind nitric oxide producing nitrogen radicals. Both oxygen and nitrogen free radicals have severed destructive effects on the cell's structural and functional components ranging from a mild effect on the cell membrane until affecting nuclei acids in the nucleus [18][19][20]. A direct correlation between levels of nitric oxide and histopathological findings could be observed.…”

Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis

“…6F). Considering the cytoplasmic distribution of GPX4 and the multidomain, transmembrane nature of TMEM16A [22], the GPX4-binding region of TMEM16A was speculated to be located in the cytoplasm. Using the Prediction of Transmembrane Helices in Proteins tool (https:// services.healthtech.dtu.dk/service.php?TMHMM-2.0), residues 755-782 within the 733-986 aa region of TMEM16A were predicted to be responsible for binding to GPX4.…”