DNA Methylation in Embryo Development: Epigenetic Impact of ART (Assisted Reproductive Technologies)

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.

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Epigenetic imprinting during assisted reproductive technologies: The effect of temporal and cumulative fluctuations in methionine cycling on the DNA methylation state

Molecular Reproduction and Development ◽

10.1002/mrd.22605 ◽

2016 ◽

Vol 83 (2) ◽

pp. 94-107 ◽

Cited By ~ 7

Author(s):

Lianne Hoeijmakers ◽

Hermannus Kempe ◽

Pernette J. Verschure

Keyword(s):

Dna Methylation ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Methylation State

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Microphysiologic systems in female reproductive biology

Experimental Biology and Medicine ◽

10.1177/1535370217697386 ◽

2017 ◽

Vol 242 (17) ◽

pp. 1690-1700 ◽

Cited By ~ 10

Author(s):

Alexandria N Young ◽

Georgette Moyle-Heyrman ◽

J Julie Kim ◽

Joanna E Burdette

Keyword(s):

Reproductive Biology ◽

Embryo Development ◽

Reproductive Tract ◽

New Technologies ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Female Reproductive Tract ◽

The Body ◽

Technological Advancement ◽

Organ Systems

Microphysiologic systems (MPS), including new organ-on-a-chip technologies, recapitulate tissue microenvironments by employing specially designed tissue or cell culturing techniques and microfluidic flow. Such systems are designed to incorporate physiologic factors that conventional 2D or even 3D systems cannot, such as the multicellular dynamics of a tissue–tissue interface or physical forces like fluid sheer stress. The female reproductive system is a series of interconnected organs that are necessary to produce eggs, support embryo development and female health, and impact the functioning of non-reproductive tissues throughout the body. Despite its importance, the human reproductive tract has received less attention than other organ systems, such as the liver and kidney, in terms of modeling with MPS. In this review, we discuss current gaps in the field and areas for technological advancement through the application of MPS. We explore current MPS research in female reproductive biology, including fertilization, pregnancy, and female reproductive tract diseases, with a focus on their clinical applications. Impact statement This review discusses existing microphysiologic systems technology that may be applied to study of the female reproductive tract, and those currently in development to specifically investigate gametes, fertilization, embryo development, pregnancy, and diseases of the female reproductive tract. We focus on the clinical applicability of these new technologies in fields such as assisted reproductive technologies, drug testing, disease diagnostics, and personalized medicine.

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Ex vivo early embryo development and effects on gene expression and imprinting

Reproduction Fertility and Development ◽

10.1071/rd04103 ◽

2005 ◽

Vol 17 (3) ◽

pp. 361 ◽

Cited By ~ 103

Author(s):

David K. Gardner ◽

Michelle Lane

Keyword(s):

Gene Expression ◽

Embryo Development ◽

Assisted Reproductive Technologies ◽

Ex Vivo ◽

Reproductive Technologies ◽

Developmental Competence ◽

Laboratory Animals ◽

Cell Physiology ◽

Mammalian Embryo

The environment to which the mammalian embryo is exposed during the preimplantation period of development has a profound effect on the physiology and viability of the conceptus. It has been demonstrated that conditions that alter gene expression, and in some instances the imprinting status of specific genes, have all previously been shown to adversely affect cell physiology. Thus, questions are raised regarding the aetiology of abnormal gene expression and altered imprinting patterns, and whether problems can be averted by using more physiological culture conditions. It is also of note that the sensitivity of the embryo to its surroundings decreases as development proceeds. Post compaction, environmental conditions have a lesser effect on gene function. This, therefore, has implications regarding the conditions used for IVF and the culture of the cleavage stage embryo. The developmental competence of the oocyte also impacts gene expression in the embryo, and therefore superovulation has been implicated in abnormal methylation and imprinting in the resultant embryo. Furthermore, the genetics and dietary status of the mother have a profound impact on embryo development and gene expression. The significance of specific animal models for human assisted reproductive technologies (ART) is questioned, given that most cattle data have been obtained from in vitro-matured oocytes and that genes imprinted in domestic and laboratory animals are not necessarily imprinted in the human. Patients treated with ART have fertility problems, which in turn may predispose their gametes or embryos to greater sensitivities to the process of ART. Whether this is from the drugs involved in the ovulation induction or from the IVF, intracytoplasmic sperm injection or culture procedures themselves remains to be determined. Alternatively, it may be that epigenetic alterations are associated with infertility and symptoms are subsequently revealed through ART. Whatever the aetiology, continued long-term monitoring of the children conceived through ART is warranted.

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Roles of steroid hormones in oviductal function

Reproduction ◽

10.1530/rep-19-0189 ◽

2020 ◽

Vol 159 (3) ◽

pp. R125-R137 ◽

Cited By ~ 4

Author(s):

Brooke E Barton ◽

Gerardo G Herrera ◽

Prashanth Anamthathmakula ◽

Jenna K Rock ◽

Anna M Willie ◽

...

Keyword(s):

Steroid Hormones ◽

Embryo Development ◽

Muscle Cell ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Farm Animals ◽

Cell Functions ◽

Laboratory Rodents ◽

Embryo Transport ◽

And Function

The oviduct (known as the fallopian tube in humans) is the site for fertilization and pre-implantation embryo development. Female steroid hormones, estrogen and progesterone, are known to modulate the morphology and function of cells in the oviduct. In this review, we focus on the actions of estrogen and progesterone on secretory, ciliated, and muscle cell functions and morphologies during fertilization, pre-implantation embryo development, and embryo transport in humans, laboratory rodents and farm animals. We review some aspects of oviductal anatomy and histology and discuss current assisted reproductive technologies (ARTs) that bypass the oviduct and their effects on embryo quality. Lastly, we review the causes of alterations in secretory, ciliated, and muscle cell functions that could result in embryo transport defects.

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PP-025 - Impact of oxygen concentration on embryo development and outcome of extended culture in assisted reproductive technologies

Reproductive BioMedicine Online ◽

10.1016/s1472-6483(16)30160-2 ◽

2016 ◽

Vol 32 ◽

pp. S13

Author(s):

Christiane Wittemer ◽

Thérèse Schweitzer ◽

Florence Lestrade ◽

Jean Pierre Ragage ◽

Richard Wasels

Keyword(s):

Oxygen Concentration ◽

Embryo Development ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Extended Culture

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Dose-dependent effects of gonadotropin on oocyte developmental competence and apoptosis

Reproduction Fertility and Development ◽

10.1071/rd11079 ◽

2011 ◽

Vol 23 (8) ◽

pp. 990 ◽

Cited By ~ 9

Author(s):

Shan Liu ◽

Huai L. Feng ◽

Dennis Marchesi ◽

Zi-Jiang Chen ◽

Avner Hershlag

Keyword(s):

Embryo Development ◽

Assisted Reproductive Technologies ◽

Cumulus Cells ◽

Reproductive Technologies ◽

Developmental Competence ◽

Beneficial Effects ◽

Nuclear Maturation ◽

High Concentrations ◽

Vitro Development

The aim of the present study was to evaluate the effect of gonadotropins (Gn) on oocyte maturation, developmental competence and apoptosis in an animal model. Bovine cumulus–oocyte complexes (COCs) were matured for 24 h in media supplemented with varying concentrations of Bravelle (B), B + Menopur (B + M) or B + Repronex (B + R) (Ferring Pharmaceuticals, Parsiappany, NJ, USA). Then, nuclear maturation, embryo development, and apoptosis in cumulus cells and oocytes were evaluated. Low to moderate Gn concentrations (75–7500 mIU mL–1) effectively improved nuclear maturation and in vitro development. Higher concentrations of Gn (75 000 mIU mL–1) did not have any added beneficial effects and nuclear maturation and blastocyst rates in the presence of these concentrations were comparable to control (P > 0.05). Most COCs showed slight apoptosis when exposed to 75, 750 and 7500 mIU mL–1 Gn; however, when the concentration was increased to 75 000 mIU mL–1, the proportion of moderately apoptotic COCs increased. In conclusion, extremely high concentrations of Gn have detrimental effects on oocyte nuclear maturation and embryo development and increase apoptosis in cumulus cells, suggesting the importance of judicious use of Gn in assisted reproductive technologies (ART).

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