Imprinted genes;
in vitro fertilization;
intracytoplasmic sperm injection;
DNA methylation;
PLAGL1;
IN-VITRO FERTILIZATION;
BECKWITH-WIEDEMANN-SYNDROME;
IMPRINTED GENE NETWORK;
TUMOR-SUPPRESSOR GENE;
SILVER-RUSSELL-SYNDROME;
GENOME-WIDE;
ABNORMAL METHYLATION;
NONIMPRINTED ALLELE;
CONTROL REGIONS;
HUMAN PLACENTAS;
D O I:
10.1016/j.fertnstert.2016.04.036
中图分类号:
R71 [妇产科学];
学科分类号:
100211 ;
摘要:
Objective: To investigate DNA methylation and expression of imprinted genes and an imprinted gene network (IGN) in neonates conceived via assisted reproductive technology (ART). Design: Case control. Setting: Research institution. Patient(s): Two hundred sixty-four cases of cord blood and/or placental villi from neonates (101 IVF, 81 ICSI, 82 naturally conceived). Intervention(s): Placentas were obtained at birth for biopsy and cord blood extraction. Main Outcome Measure(s): DNA methylation and expression of imprinted genes. Result(s): DNA methylation at the PLAGL1 differentially methylated region (DMR) was significantly higher in IVF cord blood (48.0%) compared with controls (46.0%). No differences were found in DNA methylation between conception modes for KvDMR1 and LINE-1 in cord blood and placenta as well as PLAGL1 and PEG10 in placenta villi. PLAGL1 expression was lower in both IVF and ICSI cord blood groups than in controls (relative quantification of 0.65, 0.74, 0.89, respectively). Analyzing the expression of 3 genes in a PLAGL1 regulated IGN revealed different expression between conception modes and a significant correlation to PLAGL1 expression in only one (KCNQ1OT1). Conclusion(s): Our results suggest a stability of DNA methylation at imprinted DMRs; however, we show PLAGL1 methylation/expression to be altered after ART. As PLAGL1 expression correlated with only one of the three IGN genes in cord blood, we propose there is a more complex mechanism of regulating the IGN that may involve other genes and epigenetic modifications in this tissue. Further research investigating IGN-implicated genes in various neonatal tissues is warranted to elucidate the full effects ART-induced alterations to PLAGL1 and the IGN may have on fetal growth/development. (C)2016 by American Society for Reproductive Medicine.
机构:
Univ Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Penova-Veselinovic, B.
Melton, P. E.
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机构:
Univ Western Australia, Sch Populat & Global Hlth, Perth, WA, Australia
Curtin Univ, Sch Pharm & Biomed Sci, Perth, WA, Australia
Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Melton, P. E.
Huang, R. C.
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Univ Western Australia, Fac Hlth & Med Sci, Ctr Child Hlth Res, Perth, WA, Australia
Telethon Kids Inst, Nedlands, WA, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Huang, R. C.
Yovich, J. L.
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Curtin Univ, Sch Pharm & Biomed Sci, Perth, WA, Australia
PIVET Med Ctr, Perth, WA, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Yovich, J. L.
Burton, P.
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机构:
Concept Fertil Ctr, Subiaco, WA, Australia
Edith Cowan Univ, Fac Hlth Sci, Sch Hlth & Med Sci, Perth, WA, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Burton, P.
Wijs, L. A.
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Univ Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Wijs, L. A.
Hart, R. J.
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Univ Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
Bethesda Hosp, Fertil Specialists Western Australia, Claremont, WA, AustraliaUniv Western Australia, Fac Hlth & Med Sci, Div Obstet & Gynaecol, Sci,374 Bagot Rd,2nd Floor,A Block, Perth, WA 6008, Australia
机构:
Rutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USARutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USA
Chemerinski, Anat
Garcia de Paredes, Jessica
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Rutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USARutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USA
Garcia de Paredes, Jessica
Blackledge, Kristin
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Rutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USARutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USA
Blackledge, Kristin
Douglas, Nataki C.
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Rutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USARutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USA
Douglas, Nataki C.
Morelli, Sara S.
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Rutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USARutgers New Jersey Med Sch, Dept Obstet Gynecol & Reprod Hlth, Newark, NJ 07103 USA