Imprinting alterations in sperm may not significantly influence ART outcomes and imprinting patterns in the cord blood of offspring

Abstract

An increase in imprinting disorders in children conceived though assisted reproductive technologies (ARTs) has been the subject of several reports. The transmission of imprinting errors from the sperm of infertile fathers is believed to be a possible reason for the increased occurrence of these disorders. However, whether the imprinting alterations in sperm affect ART outcomes and the imprinting of offspring is unclear. In the current study, we analyzed the methylation of H19, SNRPN and KCNQ1OT1 by pyrosequencing sperm samples from 97 infertile patients and 31 proven fertile males as well as cord blood samples from 13 infantswho were conceived by infertile parents through intracytoplasmic sperm injection (ICSI) and 30 healthy newborns who were conceived naturally. After four cases were excluded owing to the lack of a sequencing signal, the infertile patients were subgrouped into normal (69 cases) and abnormal (24 cases) imprinting groups according to the reference range set by the control group. Between the groups, there were no significant differences in ART outcomes. Significantly different levels of methylation were detected in H19, but none of the imprinted genes were determined to be outside of the methylation reference range set by the values derived from the naturally conceived controls. Three CpG loci were found to be significantly hypomethylated in the maternally imprinted gene KCNQ1OT1 in two patients from the abnormal imprinting group, none of which were caused by sperm imprinting errors. In addition, the paternal H19 gene exhibited discrepant methylation patterns between the sperm controls and the cord blood controls. Our data suggest that increased imprinting errors in the sperm of infertile patients do not have an obvious influence on ART outcomes or the imprinting of offspring.

Alterations in sperm DNA methylation, non-coding RNA expression, and histone retention mediate vinclozolin-induced epigenetic transgenerational inheritance of disease

“…In addition, no known imprinted genes correlated to the DMRs identified. As classic imprinted genes are resistant to environmental alterations in regards to DNA methylation [ 59 ], they do not appear in the differential DNA methylation regions observed.…”

DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis

“…With regard to the involvement of imprinted genes, 10 studies showed no alteration in the imprinted genes analyzed [ 24 , 43 , 45 , 53 , 55 , 58 , 61 , 65 , 66 , 71 ], while another 11 studies showed alterations in at least one of the imprinted genes [ 25 , 26 , 30 , 39 , 41 , 47 , 52 , 59 , 67 , 68 , 70 ]. In particular, among the main genes evaluated in the various studies, we encounter H19 , Insulin-like growth factor 2 ( IGF2 ), Small Nuclear Ribonucleoprotein Polypeptide N ( SNRPN ), Mesoderm Specific Transcript ( MEST ), the Potassium Voltage Differentially Methylated Region 1 ( KvDMR1 ) region of the Potassium Voltage-Gated Channel Subfamily Q Member 1 Opposite Strand / Antisense Transcript 1 ( KCNQ1OT1 ) gene, and Maternally Expressed Gene ( MEG3 ).…”

Minor DNA methylation changes are observed in spermatozoa prepared using different protocols

“…Studies focusing only on the imprinting status in spermatozoa also gave conflicting conclusions. Tang et al 44 compared the methylation of H19 , SNRPN, and KCNQ1OT in fertile and infertile men, but despite finding imprinting failures in spermatozoa, the results suggested that they are not inherited by children. On the contrary, Kobayashi et al 45 concluded that aberrant sperm DNA methylation can increase the chances of imprinting disorders, which may be inherited from the father in some cases.…”