Modulation of imprinted gene expression following superovulation

Amanda L Fortier; Serge McGraw; Flavia L Lopes; Kirsten M Niles; Mylène Landry; Jacquetta M Trasler

doi:10.1016/j.mce.2014.03.003

Modulation of imprinted gene expression following superovulation

Mol Cell Endocrinol. 2014 May 5;388(1-2):51-7. doi: 10.1016/j.mce.2014.03.003. Epub 2014 Mar 12.

Authors

Amanda L Fortier¹, Serge McGraw², Flavia L Lopes², Kirsten M Niles¹, Mylène Landry³, Jacquetta M Trasler⁴

Affiliations

¹ Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Human Genetics, McGill University, Montreal, Quebec H3H 1P3, Canada.
² Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Human Genetics, McGill University, Montreal, Quebec H3H 1P3, Canada; Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Pediatrics, McGill University, Montreal, Quebec H3H 1P3, Canada.
³ Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Pediatrics, McGill University, Montreal, Quebec H3H 1P3, Canada.
⁴ Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Human Genetics, McGill University, Montreal, Quebec H3H 1P3, Canada; Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Pediatrics, McGill University, Montreal, Quebec H3H 1P3, Canada; Research Institute at the Montreal Children's Hospital of the McGill University Health Centre and Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3H 1P3, Canada. Electronic address: jacquetta.trasler@mcgill.ca.

PMID: 24631781
DOI: 10.1016/j.mce.2014.03.003

Abstract

Although assisted reproductive technologies increase the risk of low birth weight and genomic imprinting disorders, the precise underlying causes remain unclear. Using a mouse model, we previously showed that superovulation alters the expression of imprinted genes in the placenta at 9.5days (E9.5) of gestation. Here, we investigate whether effects of superovulation on genomic imprinting persisted at later stages of development and assess the surviving fetuses for growth and morphological abnormalities. Superovulation, followed by embryo transfer at E3.5, as compared to spontaneous ovulation (controls), resulted in embryos of normal size and weight at 14.5 and 18.5days of gestation. The normal monoallelic expression of the imprinted genes H19, Snrpn and Kcnq1ot1 was unaffected in either the placentae or the embryos from the superovulated females at E14.5 or E18.5. However, for the paternally expressed imprinted gene Igf2, superovulation generated placentae with reduced production of the mature protein at E9.5 and significantly more variable mRNA levels at E14.5. We propose that superovulation results in the ovulation of abnormal oocytes with altered expression of imprinted genes, but that the coregulated genes of the imprinted gene network result in modulated expression.

Keywords: H19; Igf2; Imprinting; Mouse; Placenta; Superovulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA Methylation
Embryo, Mammalian / metabolism
Epigenesis, Genetic*
Female
Genomic Imprinting*
Insulin-Like Growth Factor II / genetics
Insulin-Like Growth Factor II / metabolism
Mice
Organ Size
Placenta / metabolism
Placentation
Pregnancy
Pregnancy Outcome
RNA, Long Noncoding / genetics
Superovulation / genetics
Superovulation / metabolism*

Substances

H19 long non-coding RNA
IGF2 protein, mouse
RNA, Long Noncoding
Insulin-Like Growth Factor II

Grants and funding

Canadian Institutes of Health Research/Canada