TY - JOUR
T1 - Low-Dose Radiation Can Cause Epigenetic Alterations Associated With Impairments in Both Male and Female Reproductive Cells
AU - Leung, Chi Tim
AU - Yang, Yi
AU - Yu, Kwan Ngok
AU - Tam, Nathan
AU - Chan, Ting Fung
AU - Lin, Xiao
AU - Kong, Richard Yuen Chong
AU - Chiu, Jill Man Ying
AU - Wong, Alice Sze Tsai
AU - Lui, Wing Yee
AU - Yuen, Karen Wing Yee
AU - Lai, Keng Po
AU - Wu, Rudolf Shiu Sun
N1 - Funding Information:
This project was supported by the Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (SMSEGL20SC02). KL was supported by the Hong Kong SAR, Macao SAR, and Taiwan Province Talented Young Scientist Program of Guangxi.
Publisher Copyright:
© 2021 Leung, Yang, Yu, Tam, Chan, Lin, Kong, Chiu, Wong, Lui, Yuen, Lai and Wu.
PY - 2021/8/2
Y1 - 2021/8/2
N2 - Humans are regularly and continuously exposed to ionizing radiation from both natural and artificial sources. Cumulating evidence shows adverse effects of ionizing radiation on both male and female reproductive systems, including reduction of testis weight and sperm count and reduction of female germ cells and premature ovarian failure. While most of the observed effects were caused by DNA damage and disturbance of DNA repairment, ionizing radiation may also alter DNA methylation, histone, and chromatin modification, leading to epigenetic changes and transgenerational effects. However, the molecular mechanisms underlying the epigenetic changes and transgenerational reproductive impairment induced by low-dose radiation remain largely unknown. In this study, two different types of human ovarian cells and two different types of testicular cells were exposed to low dose of ionizing radiation, followed by bioinformatics analysis (including gene ontology functional analysis and Ingenuity Pathway Analysis), to unravel and compare epigenetic effects and pathway changes in male and female reproductive cells induced by ionizing radiation. Our findings showed that the radiation could alter the expression of gene cluster related to DNA damage responses through the control of MYC. Furthermore, ionizing radiation could lead to gender-specific reproductive impairment through deregulation of different gene networks. More importantly, the observed epigenetic modifications induced by ionizing radiation are mediated through the alteration of chromatin remodeling and telomere function. This study, for the first time, demonstrated that ionizing radiation may alter the epigenome of germ cells, leading to transgenerational reproductive impairments, and correspondingly call for research in this new emerging area which remains almost unknown.
AB - Humans are regularly and continuously exposed to ionizing radiation from both natural and artificial sources. Cumulating evidence shows adverse effects of ionizing radiation on both male and female reproductive systems, including reduction of testis weight and sperm count and reduction of female germ cells and premature ovarian failure. While most of the observed effects were caused by DNA damage and disturbance of DNA repairment, ionizing radiation may also alter DNA methylation, histone, and chromatin modification, leading to epigenetic changes and transgenerational effects. However, the molecular mechanisms underlying the epigenetic changes and transgenerational reproductive impairment induced by low-dose radiation remain largely unknown. In this study, two different types of human ovarian cells and two different types of testicular cells were exposed to low dose of ionizing radiation, followed by bioinformatics analysis (including gene ontology functional analysis and Ingenuity Pathway Analysis), to unravel and compare epigenetic effects and pathway changes in male and female reproductive cells induced by ionizing radiation. Our findings showed that the radiation could alter the expression of gene cluster related to DNA damage responses through the control of MYC. Furthermore, ionizing radiation could lead to gender-specific reproductive impairment through deregulation of different gene networks. More importantly, the observed epigenetic modifications induced by ionizing radiation are mediated through the alteration of chromatin remodeling and telomere function. This study, for the first time, demonstrated that ionizing radiation may alter the epigenome of germ cells, leading to transgenerational reproductive impairments, and correspondingly call for research in this new emerging area which remains almost unknown.
KW - environmental radiation
KW - epigenetic
KW - ovarian
KW - reproductive impairments
KW - testicular
UR - https://doi.org/10.3389/fgene.2022.945115
UR - http://www.scopus.com/inward/record.url?scp=85112763557&partnerID=8YFLogxK
U2 - 10.3389/fgene.2021.710143
DO - 10.3389/fgene.2021.710143
M3 - Journal article
AN - SCOPUS:85112763557
SN - 1664-8021
VL - 12
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 710143
ER -