Ovulation Induction Changes Epigenetic Marks of Imprinting Genes in Mice Fetus Organs

Document Type : Original Article

Authors

1 Department of Biology, Fars Science and Research Branch, Islamic Azad University, Fars, Iran;Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran

2 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;4Department of Cell and Molecular Biology, School of Biology, College of Science, University of Te

3 Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

4 5School of Nursing and Midwifery, Guilan University of Medical Sciences, Rasht, Iran

5 6Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Abstract

Objective
Genomic imprinting is an epigenetic phenomenon that plays a critical role in normal development of embryo. Using exogenous hormones during assisted reproductive technology (ART) can change an organism hormonal profile and subsequently affect epigenetic events. Ovarian stimulation changes gene expression and epigenetic pattern of imprinted genes in the organs of mouse fetus.
Materials and Methods
For this experimental study, expression of three imprinted genes H19, Igf2 (Insulin-like growth factor 2) and Cdkn1c (Cyclin-dependent kinase inhibitor 1C), which have important roles in development of placenta and embryo, and the epigenetic profile of their regulatory region in some tissues of 19-days-old female fetuses, from female mice subjected to ovarian stimulation, were evaluated by quantitative reverse-transcription PCR (qRT-PCR) and Chromatin immunoprecipitation (ChIP) methods.
Results
H19 gene was significantly lower in heart (P < 0.05), liver (P < 0.05), lung (P < 0.01), placenta (P < 0.01) and ovary (P < 0.01). It was significantly higher in kidney of ovarian stimulation group compared to control fetuses (P < 0.05). Igf2 expression was significantly higher in brain (P < 0.05) and kidney (P < 0.05), while it was significantly lower in lung of experimental group fetuses in comparison with control fetuses (P < 0.05). Cdkn1c expression was significantly higher in lung (P < 0.05). It was significantly decreased in placenta of experimental group fetuses rather than the control fetuses (P < 0.05). Histone modification data and DNA methylation data were in accordance to the gene expression profiles.
Conclusion
Results showed altered gene expressions in line with changes in epigenetic pattern of their promoters in the ovarian stimulation group, compared to normal cycle.

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