Evaluation of Global DNA Methylation and Gene Expression of <i>Izumo1</i> and <i>Izumo1r</i> in Gonads after High- and Low-Dose Radiation in Neonatal Mice

The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed...

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Main Authors: Akifumi Nakata, Keisuke Sato, Yohei Fujishima, Valerie Goh Swee Ting, Kanade Nakayama, Kentaro Ariyoshi, Chizuru Tsuruoka, Yi Shang, Daisuke Iizuka, Shizuko Kakinuma, Hideaki Yamashiro, Tomisato Miura
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/10/12/1270
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Summary:The intergenerational effects from chronic low-dose exposure are matters of concern. It is thus important to elucidate the radiation-induced effects of germ cell maturation, fertilization and embryonic development. It is well known that DNA methylation levels in CpG sites in gametes are reprogrammed in stages during their maturity. Furthermore, the binding of <i>Izumo</i> on the surface of sperm and <i>Juno</i> on the surface of oocytes is essential for fertilization. Thus, there is a possibility that these genes are useful indicators to evaluate fertility in mice after irradiation exposure. Therefore, in this study, we analyzed global DNA methylation patterns in the testes and gene expression of <i>Izumo1</i> and <i>Izumo1r</i> (<i>Juno</i>) in the gonads of mice after neonatal acute high-dose ionizing radiation (HDR) and chronic low-dose ionizing radiation (LDR). One-week-old male and female mice were irradiated with a total dose of 4 Gy, with acute HDR at 7 days at a dose rate of 30 Gy/h and LDR continuously at a dose rate of 6 mGy/h from 7 to 35 days. Their gonads were subsequently analyzed. The results of global DNA methylation patterns in the testes showed that methylation level increased with age in the control group, the LDR group maintained its DNA methylation level, and the HDR group showed decreased DNA methylation levels with age. In the control group, the gene expression level of <i>Izumo1</i> in the testis did not show age-related changes, although there was high expression at 100 days of age. However, in the LDR group, the expression level recovered after the end of irradiation, while it remained low regardless of age in the HDR group. Conversely, gene expression of <i>Izumo1r</i> (<i>Izumo1</i> receptor) in the ovary decreased with age in the control group. Although the gene expression of <i>Izumo1r</i> decreased with age in the LDR group, it remained low in the HDR group. Our results indicate that LDR can induce different DNA methylation patterns, and both high- and low-dose radiation before sexual maturity might affect gametogenesis and fertility.
ISSN:2079-7737