Gerald Phillip Schatten Pittsburgh Development Center Obstetrics, Gynecology & Reproductive Sciences Division of Developmental & Regenerative Medicine School of Medicine Pittsburgh (PA), USA

Declared receipt of grants and contracts from the National Institute of Health The role of epigenetic and imprinting in extended culture: would it affect the health of the child?

G.P. Schatten (USA) Paternal Stress Exposure Alters Sperm MicroRNA Content and Reprograms Offspring HPA Stress Axis Regulation. Rodgers et al. The Journal of Neuroscience, 33(21): 9003- 9012; doi: 10.1523/JNEUROSCI.0914-13.2013 The Tutsi genocide and transgenerational transmission of maternal stress: and of the HPA axis

The World Journal of Biological Psychiatry, May 2014, Vol. 15, No. 4 : Pages 334 -345

Nader Perroud , Eugene Rutembesa , Ariane Paoloni- Giacobino , Jean Mutabaruka , Léon Mutesa , Ludwig Stenz , Alain Malafosse , Félicien Karege

(doi: 10.3109/15622975.2013.866693)

Brian G. Dias , Stephanie A. Maddox , Torsten Klengel , Kerry J. Ressler Trends in Neurosciences, Volume 38, Issue 2, 2015, 96 - 107 Epigenetic mechanisms underlying learning and the inheritance of learned behaviors

A summary of imprinted gene functions during embryogenesis.

Robert N. Plasschaert, and Marisa S. Bartolomei Development 2014;141:1805-1813 Genomic imprinting is the epigenetic phenomenon by which certain genes are expressed in a parent -of -origin-specific manner. If the allele inherited from the father is imprinted, it is thereby silenced, and only the allele from the mother is expressed.

Establishment, maintenance and erasure of genomic imprints during mouse development.

Robert N. Plasschaert, and Marisa S. Bartolomei Development 2014;141:1805-1813

Differential methylation in glucoregulatory genes of offspring born before vs. after maternal gastrointestinal bypass surgery

a b,c b,c d Frédéric Guénard , Yves Deshaies , Katherine Cianflone , John G. Kral , Picard c,e a,1 Marceau , and Marie-Claude Vohl

Proc Natl Acad Sci U S A. 2013 Jul 9; 110(28): 11439–11444. Published online 2013 May 28. doi: 10.1073/pnas.1216959110 PMCID: PMC3710842 Mechanisms Linking Fetal Nutrient Supply to Later Phenotypes Uteroplacental insufficiency decreases availability of key substrates such as oxygen and glucose to the fetus. Altered substrate availability (e.g., decreased acetyl Co -A or S -Adenosyl ...

Oliver J. Rando , Rebecca A. Simmons

I’m Eating for Two: Parental Dietary Effects on Offspring Metabolism

Cell, 161, 2015, 93 – 105 http://dx.doi.org/10.1016/j.cell.2015.02.021

WHY SHOULD WE BE CONCERNED ABOUT EPIGENETIC ALTERATIONS IN ART OFFSPRING? WHY SHOULD WE BE CONCERNED ABOUT EPIGENETIC ALTERATIONS IN ART OFFSPRING?

Differences from Natural Conception Culture Media Plastics, Gases, pH, etc. IVF vs ICSI vs ELSI Sperm Preparation Patient Population

Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc.

Gerald Schatten Oregon Regional Research Center and Oregon Health Sciences University Portland OR, USA

Epigenetics: Cellular memory erased in human Wolf Reik & Gavin Kelsey

Nature 511, 540–541 2014 doi:10.1038/nature13648

Are imprinting disorders more prevalent after human in vitro fertilization or intracytoplasmic sperm injection?

Jan P. W. Vermeiden, Ph.D. and Rob E. Bernardus, M.D., Ph.D. Nij Barrahus Fertility Center, Wolvega, the Netherlands

Eight epidemiologic studies were suitable to calculate the weighted relative risk for the birth of a child with Beckwith Wiedemann syndrome following IVF or ICSI compared with the risk in the normal population. This relative risk was 5.2 (95% CI 1.6–7.4). In one study the relative risk was corrected for parents’ fertility problems and no significant association was found. Data on the Silver-Russell syndrome are too sparse to draw conclusions, but a positive association with IVF or ICSI treatment is probable. No significant associations were found between the incidences of the Angelman and Prader- Willi syndromes and IVF or ICSI treatments. Children with Prader-Willi syndrome or Angelman syndrome are more likely to be born to parents with fertility problems. All retinoblastomas in children born after IVF or ICSI could be explained by de novo mutations in the RB1 gene and were not associated with imprinted genes. Imprinted diseases result from methylation errors already present in sperms or oocytes.

There is no proof of a causal relationship between imprinted diseases and IVF or ICSI treatments. (Fertil Steril 2013;99:642–51.)

Epigenomics: Roadmap for regulation Romanoski et al. 518, 314–316 (19 February 2015) doi:10.1038/518314a Tissues and cell types profiled in the Roadmap Epigenomics Consortium.

Roadmap Epigenomics Consortium et al. Nature 518, 317-330 (2015) doi:10.1038/nature14248 Epigenomic enrichments of genetic variants associated with diverse traits.

Roadmap Epigenomics Consortium et al. Nature 518 , 317-330 (2015) doi:10.1038/nature14248 Published by AAAS T H Murray Science 2014;343:1208-1210

Summary—ART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.

The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders Asli Uyar a,b and Emre Seli aPMCID: PMC4123998 Curr Opin Obstet Gynecol. 2014 Jun; 26(3): 210–221. The role of epigenetic and imprinting in extended embryo culture:

Would it affect the health of the child?

YES, in animal pups…

The role of epigenetic and imprinting in extended embryo culture:

Would it affect the health of the child?

YES, in animal pups…