TY - JOUR
T1 - DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm
AU - Kobayashi, Hisato
AU - Hiura, Hitoshi
AU - John, Rosalind M.
AU - Sato, Akiko
AU - Otsu, Eiko
AU - Kobayashi, Naoko
AU - Suzuki, Rei
AU - Suzuki, Fumihiko
AU - Hayashi, Chika
AU - Utsunomiya, Takafumi
AU - Yaegashi, Nobuo
AU - Arima, Takahiro
N1 - Funding Information:
We thank Miss M Nasu for technical assistance and all the members of our laboratory for their support and valuable suggestions. Patients’ agreement was obtained and all work was performed with the approval of the institutional ethics committee and Japan Society of Obstetrics and Gynecology. This work was supported by grants from the Ministry of Health and Welfare of Japan (19390423 and 20017003), Japan Science and Technology Agency (JST), Avon Support Foundation, Suzuken Memorial Foundation, Takeda Science Foundation, Children’s Cancer Association of Japan, Uehara Memorial Foundation, Kampo Medical Foundation, Osteoporosis Foundation, Hiromi Foundation, Daiwa Foundation, NIG Cooperative Research Program (2008-B), Smoking Research Foundation, Nakatomi Foundation, The Salt Science Research Foundation (0829), Nestle Nutrition Council Japan, Kobayashi Institute for Innovative Cancer Chemotherapy, Yamada Bee Farm Grant for Honeybee Research (TA) and Sagawa Cancer Foundation, Suzuken Memorial Foundation (YN). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing the report.
PY - 2009
Y1 - 2009
N2 - There is an increased prevalence of imprinting disorders, such as Beckwith-Wiedemann syndrome, associated with human assisted reproductive technologies (ART). Work on animal models suggests that in vitro culture may be the source of these imprinting errors. However, in this study we report that, in some cases, the errors are inherited from the father. We analyzed DNA methylation at seven autosomal imprinted loci and the XIST locus in 78 paired DNA samples. In seven out of seventeen cases where there was abnormal DNA methylation in the ART sample (41%), the identical alterations were present in the parental sperm. Furthermore, we also identified DNA sequence variations in the gene encoding DNMT3L, which were associated with the abnormal paternal DNA methylation. Both the imprinting errors and the DNA sequence variants were more prevalent in patients with oligospermia. Our data suggest that the increase in the incidence of imprinting disorders in individuals born by ART may be due, in some cases, to the use of sperm with intrinsic imprinting mutations.
AB - There is an increased prevalence of imprinting disorders, such as Beckwith-Wiedemann syndrome, associated with human assisted reproductive technologies (ART). Work on animal models suggests that in vitro culture may be the source of these imprinting errors. However, in this study we report that, in some cases, the errors are inherited from the father. We analyzed DNA methylation at seven autosomal imprinted loci and the XIST locus in 78 paired DNA samples. In seven out of seventeen cases where there was abnormal DNA methylation in the ART sample (41%), the identical alterations were present in the parental sperm. Furthermore, we also identified DNA sequence variations in the gene encoding DNMT3L, which were associated with the abnormal paternal DNA methylation. Both the imprinting errors and the DNA sequence variants were more prevalent in patients with oligospermia. Our data suggest that the increase in the incidence of imprinting disorders in individuals born by ART may be due, in some cases, to the use of sperm with intrinsic imprinting mutations.
UR - http://www.scopus.com/inward/record.url?scp=70450252294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70450252294&partnerID=8YFLogxK
U2 - 10.1038/ejhg.2009.68
DO - 10.1038/ejhg.2009.68
M3 - Article
C2 - 19471309
AN - SCOPUS:70450252294
VL - 17
SP - 1582
EP - 1591
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 12
ER -