Assisted reproductive technologies impair the expression and methylation of insulin-induced gene 1 and sterol regulatory element-binding factor 1 in the fetus and placenta.
OBJECTIVE
To evaluate the cholesterol metabolism linked to assisted reproductive technology (ART) by analyzing the expression levels and DNA methylation patterns of the insulin-induced gene (INSIG), sterol regulatory element-binding protein (SREBP), and SREBP cleavage-activating protein in the fetus and placenta.


METHODS
Experimental research study.


METHODS
An IVF center, university-affiliated teaching hospital.


METHODS
Four patients groups were recruited: pregnancies after IVF/intracytoplasmic sperm injection (ICSI) (n = 55), natural pregnancies (n = 40), multifetal reduction after IVF/ICSI (n = 56), and multifetal reduction after controlled ovarian hyperstimulation (COH) (n = 42).


METHODS
Expression and DNA methylation of INSIG-SREBP- SREBP cleavage-activating protein in the fetus and placenta samples were determined.


METHODS
The expression and DNA methylation patterns were tested by real-time quantitative polymerase chain reaction (PCR) and pyrosequencing.


RESULTS
In the ICSI treatment group, significantly higher levels of triglycerides and apolipoprotein-B were observed in cord blood compared with controls. Meanwhile, in ICSI-conceived fetuses, the expression of INSIG1 was significantly higher, and methylation rates were lower, than in the IVF and control groups. Furthermore, in the placenta, the INSIG1 and SREBF1 transcripts were also significantly higher with lower methylation rates in the ICSI group than in the IVF and control groups.


CONCLUSIONS
Our results indicated that the dysregulation of INSIG1 and SREBF1 caused by ART were observed not only in the fetus but also in the placenta, primarily in the ICSI group. However, the long-term sequelae of this dysregulation should be closely followed.
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, People's Republic of China.
Hangying
H
Lou
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Fang
F
Le
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Yingming
Y
Zheng
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Lejun
L
Li
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Liya
L
Wang
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Ning
N
Wang
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, People's Republic of China.
Yimin
Y
Zhu
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, People's Republic of China.
Hefeng
H
Huang
Center of Reproductive Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, People's Republic of China. Electronic address: jinfan@zju.edu.cn.
Fan
F
Jin
D000328:Adult; D002784:Cholesterol / Q000378:metabolism*; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D005333:Fetus; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*
C108626:INSIG1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D002784:Cholesterol
Assisted reproductive technology (ART); fetus; insulin-induced gene 1 (INSIG1); placenta; sterol regulatory element binding protein 1 (SREBP1)