Variation in DNA methylation in the KvDMR1 (ICR2) region in first-trimester human pregnancies

Levels of DNA methylation in the KvDMR1 are variable in embryonic and extraembryonic tissues from first trimester human pregnancies. Term placental villi showed a normal methylation at KVDMR1 region.

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Volume 111, Issue 6, Pages 1186–1193

Authors:

Cristiana Libardi Miranda Furtado, Ph.D., Karina Bezerra Salomão, Ph.D., Carolina Gennari Verruma, M.Sc., Sarah Blima Paulino Leite, Ph.D., Álvaro Fabrício Lopes Rios, Ph.D., Monika Bialecka, Ph.D., Ioannis Moustakas, M.Sc., Hailiang Mei, Ph.D., Claudia Cristina Paro de Paz, Ph.D., Geraldo Duarte, M.D., Ph.D., Susana M. Chuva de Sousa Lopes, Ph.D., Ester Silveira Ramos, M.D., Ph.D.

Abstract:

Objective

To investigate the levels of DNA methylation in the KvDMR1 (KvLQT1 differentially methylated region 1) in embryonic and extra-embryonic tissues.

Design

Cross-sectional study.

Setting

University medical center and clinical hospital.

Patient(s)

Embryonic and/or extraembryonic tissues (umbilical cord, chorionic villus, chorion, decidua, and/or amnion) collected from 27 first-trimester pregnancies (up to 12 weeks of gestation, single embryos) from elective abortions, extravillous trophoblasts (EVTs) from the top of individual chorionic villi, and chorionic villi from 10 normal full-term placentas collected after birth.

Intervention(s)

None.

Main Outcome Measure(s)

DNA methylation of the KvDMR1 region evaluated using quantitative analysis of DNA methylation followed by real-time polymerase chain reaction (qAMP) and bisulfite sequencing (bis-seq) analysis.

Result(s)

The results showed variability in KvDMR1 DNA methylation in different tissues from the same pregnancy. The average of DNA methylation was not different between the embryo, umbilical cord, amnion, and chorionic villi, despite the relatively low level of methylation observed in the amnion (33.50% ± 14.48%). Chorionic villi from term placentas showed a normal methylation pattern at KvDMR1 (42.60% ± 6.08%). The normal methylation pattern at KvDMR1 in chorionic villi (as well as in EVTs) from first-trimester placentas was confirmed by bis-seq.

Conclusion(s)

Our results highlight an existing heterogeneity in DNA methylation of the KvDMR1 region during first trimester and a consistent hypomethylation in the amnion in this period of gestation.


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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