scholarly journals Analyses of child cardiometabolic phenotype following assisted reproductive technologies using a pragmatic trial emulation approach

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jonathan Yinhao Huang ◽  
Shirong Cai ◽  
Zhongwei Huang ◽  
Mya Thway Tint ◽  
Wen Lun Yuan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Pragmatic Trial ◽  
Reproductive Technologies ◽  
Negative Control ◽  
Polygenic Risk Score ◽  
Weak Selection ◽  
Comparison Groups ◽  
Metabolic Biomarkers

AbstractAssisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (−0.5 SD [95% CI: −0.7, −0.2]), lighter (−0.6 SD [−0.9, −0.3]) and have lower skinfold thicknesses (e.g. −14% [−24%, −3%] suprailiac), and blood pressure (−3 mmHg [−6, −0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype.

Modifiable aspects of assisted reproductive technologies (ART) procedures lead to alterations in placental DNA methylation

2014 ◽  
Vol 102 (3) ◽  
pp. e42-e43
Author(s):  
R.S. Weinerman ◽  
J. Ghosh ◽  
S. Song ◽  
M. Truongcao ◽  
C. Sapienza ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies

scholarly journals DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sebastian Canovas ◽  
Elena Ivanova ◽  
Raquel Romar ◽  
Soledad García-Martínez ◽  
Cristina Soriano-Úbeda ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Cell Number ◽  
Rna Seq ◽  
Methylation Analysis ◽  
Number Of Children ◽  
Methylation Patterns

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.

Comparison of Genome-Wide and Gene-Specific DNA Methylation between Pregnancies Conceived Naturally Versus ART (Assisted Reproductive Technologies)

Placenta ◽  
2013 ◽  
Vol 34 (9) ◽  
pp. A56 ◽  
Author(s):  
Nir Melamed ◽  
Sanaa Choufani ◽  
Louise Wilkins-Haug ◽  
Ellen Greenblatt ◽  
Rosanna Weksberg
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Genome Wide

Assisted reproductive technologies do not enhance the variability of DNA methylation imprints in human

2009 ◽  
Vol 47 (6) ◽  
pp. 371-376 ◽  
Author(s):  
S. Tierling ◽  
N. Y. Souren ◽  
J. Gries ◽  
C. LoPorto ◽  
M. Groth ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies

scholarly journals Culture Medium and Sex Drive Epigenetic Reprogramming in Preimplantation Bovine Embryos

2021 ◽  
Vol 22 (12) ◽  
pp. 6426
Author(s):  
Sebastian Canovas ◽  
Elena Ivanova ◽  
Meriem Hamdi ◽  
Fernando Perez-Sanz ◽  
Dimitrios Rizos ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Developmental Process ◽  
Reproductive Technologies ◽  
Sexually Dimorphic ◽  
Element Analysis ◽  
Global Methylation ◽  
The Impact

Assisted reproductive technologies impact transcriptome and epigenome of embryos and can result in long-term phenotypic consequences. Whole-genome DNA methylation profiles from individual bovine blastocysts in vivo- and in vitro-derived (using three sources of protein: reproductive fluids, blood serum and bovine serum albumin) were generated. The impact of in vitro culture on DNA methylation was analyzed, and sex-specific methylation differences at blastocyst stage were uncovered. In vivo embryos showed the highest levels of methylation (29.5%), close to those produced in vitro with serum, whilst embryos produced in vitro with reproductive fluids or albumin showed less global methylation (25–25.4%). During repetitive element analysis, the serum group was the most affected. DNA methylation differences between in vivo and in vitro groups were more frequent in the first intron than in CpGi in promoters. Moreover, hierarchical cluster analysis showed that sex produced a stronger bias in the results than embryo origin. For each group, distance between male and female embryos varied, with in vivo blastocyst showing a lesser distance. Between the sexually dimorphic methylated tiles, which were biased to X-chromosome, critical factors for reproduction, developmental process, cell proliferation and DNA methylation machinery were included. These results support the idea that blastocysts show sexually-dimorphic DNA methylation patterns, and the known picture about the blastocyst methylome should be reconsidered.

scholarly journals Author response: DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids

2017 ◽  
Author(s):  
Sebastian Canovas ◽  
Elena Ivanova ◽  
Raquel Romar ◽  
Soledad García-Martínez ◽  
Cristina Soriano-Úbeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Author Response

The influence of in vitro fertilization and embryo culture on the embryo epigenetic constituents and the possible consequences in the bovine model

2017 ◽  
Vol 8 (4) ◽  
pp. 411-417 ◽  
Author(s):  
M.-A. Sirard
Keyword(s):  
Dna Methylation ◽  
Assisted Reproductive Technologies ◽  
Genetic Model ◽  
Culture Media ◽  
Reproductive Technologies ◽  
The Body ◽  
Model Systems ◽  
Gene Perturbations

Medically assisted reproductive technologies, such as in vitro embryo production, are increasingly being used to palliate infertility. Eggs are produced following a hormonal regimen that stimulates the ovaries to produce a large number of oocytes. Collected oocytes are then fertilized in vitro and allowed to develop in vitro until they are either frozen or transferred to mothers. There are controversial reports on the adverse impacts of these technologies on early embryos and their potential long-term effects. Using newly developed technological platforms that enable global gene expression and global DNA methylation profiling, we evaluated gene perturbations caused by such artificial procedures. We know that cells in the early embryo produce all cells in the body and are able to respond to their in vitro environment. However, it is not known whether gene perturbations are part of a normal response to the environment or are due to distress and will have long-term impacts. While the mouse is an established genetic model used for quality control of culture media in clinics, the bovine is a large mono-ovulating mammal with similar embryonic kinetics as humans during the studied developmental window. These model systems are critical to understand the effects of assisted reproduction without the confounding impact of infertility and without the limitations imposed by the scarcity of donated human samples and ethical issues. The data presented in this review come mostly from our own experimentation, publications, and collaborations. Together they demonstrate that the in vitro environment has a significant impact on embryos at the transcriptomic level and at the DNA methylation level.

scholarly journals On the origin of sperm epigenetic heterogeneity

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. R71-R78 ◽  
Author(s):  
Sandra Laurentino ◽  
Jennifer Borgmann ◽  
Jörg Gromoll
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Cancer Biology ◽  
Assisted Reproductive Technologies ◽  
Human Sperm ◽  
Cell Types ◽  
Reproductive Technologies ◽  
Aberrant Dna Methylation ◽  
Near Future ◽  
Sperm Epigenetics

AbstractThe influence of epigenetic modifications on reproduction and on the function of male germ cells has been thoroughly demonstrated. In particular, aberrant DNA methylation levels in sperm have been associated with abnormal sperm parameters, lower fertilization rates and impaired embryo development. Recent reports have indicated that human sperm might be epigenetically heterogeneous and that abnormal DNA methylation levels found in the sperm of infertile men could be due to the presence of sperm populations with different epigenetic quality. However, the origin and the contribution of different germ cell types to this suspected heterogeneity remain unclear. In this review, we focus on sperm epigenetics at the DNA methylation level and its importance in reproduction. We take into account the latest developments and hypotheses concerning the functional significance of epigenetic heterogeneity coming from the field of stem cell and cancer biology and discuss the potential importance and consequences of sperm epigenetic heterogeneity for reproduction, male (in)fertility and assisted reproductive technologies (ART). Based on the current information, we propose a model in which spermatogonial stem cell variability, either intrinsic or due to external factors (such as endocrine action and environmental stimuli), can lead to epigenetic sperm heterogeneity, sperm epimutations and male infertility. The elucidation of the precise causes for epimutations, the conception of adequate therapeutic options and the development of sperm selection technologies based on epigenetic quality should be regarded as crucial to the improvement of ART outcome in the near future.

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