Superovulation induces defective methylation in line-1 retrotransposon elements in blastocyst

Abstract

BackgroundSeries of epigenetic events happen during preimplantation development. Therefore assistant reproduction techniques (ART) have the potential to disrupt epigenetic regulation during embryo development. The purpose of this study was to investigate whether defects in methylation patterns in blastocyst due to superovulation originate from abnormal expression of Dnmts.MethodsLow- (6 IU) and high- (10 IU) dosage of PMSG was used to stimulate the female mice. The metaphase II(MII) oocytes, zygotes and blastocyst stage embryos were collected. Global methylation and methylation at H3K9 in zygote, and methylation at repeated sequence Line 1 and IAP in blastocysts were assayed. In addition, expression of Dnmts was examined in oocytes and zygotes.ResultsGlobal DNA methylation and methylation at H3K9 in zygotes derived from females after low- or high-dosage hormone treatment were unaltered compared to that in controls. Moreover, DNA methylation at IAP in blastocysts was also unaffected, regardless of hormone dosage. In contrast, methylation at Line1 decreased when high-dose hormone was administered. Unexpectedly, expression of Dnmt3a, Dnmt3b, Dnmt3L as well as maintenance Dnmt1o in oocytes and zygotes was not disrupted.ConclusionsThe results suggest that defects in embryonic methylation patterns do not originate from the disruption of Dnmt expression.

Supraphysiological estradiol level in ovarian stimulation cycles affects the birthweight of neonates conceived through subsequent frozen‐thawed cycles: a retrospective study

“…On the day of triggering, the median peak E 2 level was 4389 (2779-6307.5) pg/ml and the mean progesterone level 1.46 AE 1.71 ng/ml. The median oocyte number was 13 (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The number of oocytes was significantly associated Supporting Information Tables S2 and S5), the E 2 level as a continuous variable was negatively associated with both the z-score and the birthweight of the newborns (adjusted P-value 0.009 and 0.01, respectively).…”

“…Superovulation might be a source of developing epigenetic disorders in embryos derived from ART . It may partially explain the mechanism by which COS affected birthweight.…”

“…Superovulation might be a source of developing epigenetic disorders in embryos derived from ART. 10,11,13,29 It may partially explain the mechanism by which COS affected birthweight. The methylation and expression of imprinted regions have been linked with the phenotypes of fetal growth, [30][31][32] which were suggested to contribute to the developmental programming of chronic disease in adulthood.…”

Superovulation alters embryonic poly(A)-binding protein (Epab) and poly(A)-binding protein, cytoplasmic 1 (Pabpc1) gene expression in mouse oocytes and early embryos

“…In addition, superovulation leads to delayed in vitro blastocyst hatching, decreased in vivo blastocyst formation, lower implantation rates, more resorption sites and 40% fetal development retardation compared with naturally ovulating females (Van der Auwera and D'Hooghe 2001). Superovulation also disrupts the methylation status or expression levels of certain genes, such as H19 (Fauque et al 2007;Fortier et al 2008), PEG1 (Sato et al 2007), Snrpn (Fortier et al 2008), insulin-like growth factor 2 (Igf2) (Fortier et al 2008) and long interspersed nuclear element 1 (Line1) (Liang et al 2013), in human or mouse oocytes, embryos or placentas. All studies in this field are summarised in Fig.…”

Non-Genetic Inheritance, Fertility and Assisted Reproductive Technologies

“…Data from animal models supports the notion that 'over-riding' of the natural hormonal cycle is in itself associated with molecular changes to the oocyte which may impact on development of the embryo and pregnancy. A mouse study established that the superovulation process altered the epigenetic marks in oocytes with disrupted H19 expression and loss of methylation in several maternally imprinted genes in a dose-dependent manner [54]. Further, studies on both mice and cows have demonstrated changes to the epigenetic marks in the oocytes as well as fundamental changes in the epigenetic machinery of the oocyte obtained from superovulation [55].…”