Abstract
The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns’ heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.
Highlights
Assisted reproductive technology (ART) involves fertilizing a human egg in vitro and the transplantation of the resulting embryo into the uterus for conception (Van Voorhis, 2007; Belva et al, 2016; Boulet et al, 2016; De Geyter et al, 2018)
After the methylation beta level (0–1) was divided into approximately 20 intervals, the results revealed that such hypomethylation in the assisted reproductive technology (ART) group was mainly caused by the decreased ratio in CpG sites with high DNA methylation levels, with 29.61% in the ART group and 30.52% in the control group, and the increased ratio in the CpG site with low and medium DNA methylation levels, with 70.39% in the ART group and 69.48% in the control group (Figures 1E,F)
In a comparison involving the imprinted and housekeeping gene database, we identified 3 differential methylation sites (DMSs) located in 2 imprinted genes (Table 2) and 28 DMSs located in 26 housekeeping genes (Table 3)
Summary
Assisted reproductive technology (ART) involves fertilizing a human egg in vitro and the transplantation of the resulting embryo into the uterus for conception (Van Voorhis, 2007; Belva et al, 2016; Boulet et al, 2016; De Geyter et al, 2018). Epidemiological and animal experiments show that the early stage of fetal development is sensitive to changes in the environment and that the environmental abnormalities suffered during this period may lead to problems later in life (Faulk and Dolinoy, 2011; Hanson and Gluckman, 2014; Grandjean et al, 2015; Heindel et al, 2017; Li T. et al, 2019) During this sensitive period, adverse environmental stimulation may affect cell proliferation and lineage differentiation by affecting normal epigenetic reprogramming processes, leading to abnormal epigenetic modification levels and permanent changes in gene expression patterns (Yamazaki et al, 2003; Hanson and Gluckman, 2014; Nelissen et al, 2014; Koot et al, 2016). Epidemiological studies have reported the abnormal development of the immune system (Tan et al, 2016; Kollmann et al, 2017; Pathare et al, 2017), increased risk of neurological diseases, the presence of metabolic abnormalities, and the presence of congenital anomalies in ART-assisted human offspring, including autism spectrum disorders, intellectual disability, specific congenital heart defects, cardiovascular disease, and metabolic disorder (Sandin et al, 2013; Tararbit et al, 2013; Guo et al, 2017; Liu et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
