scholarly journals Genomic imprints as a model for the analysis of epigenetic stability during assisted reproductive technologies

Reproduction ◽  
2012 ◽  
Vol 144 (4) ◽  
pp. 393-409 ◽  
Author(s):  
Michelle M Denomme ◽  
Mellissa R W Mann
Keyword(s):  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Cellular Mechanisms ◽  
Apparent Lack ◽  
Epigenetic Instability ◽  
Genomic Imprints ◽  
Epigenetic Disruption ◽  
Genome Scale

Gamete and early embryo development are important stages when genome-scale epigenetic transitions are orchestrated. The apparent lack of remodeling of differential imprinted DNA methylation during preimplantation development has lead to the argument that epigenetic disruption by assisted reproductive technologies (ARTs) is restricted to imprinted genes. We contend that aberrant imprinted methylation arising from assisted reproduction or infertility may be an indicator of more global epigenetic instability. Here, we review the current literature on the effects of ARTs, including ovarian stimulation,in vitrooocyte maturation, oocyte cryopreservation, IVF, ICSI, embryo culture, and infertility on genomic imprinting as a model for evaluating epigenetic stability. Undoubtedly, the relationship between impaired fertility, ARTs, and epigenetic stability is unquestionably complex. What is clear is that future studies need to be directed at determining the molecular and cellular mechanisms giving rise to epigenetic errors.

scholarly journals Reproductive technologies, female infertility, and the risk of imprinting-related disorders

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Patricia Fauque ◽  
Jacques De Mouzon ◽  
Aviva Devaux ◽  
Sylvie Epelboin ◽  
Marie-José Gervoise-Boyer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Intrauterine Insemination ◽  
Reproductive Technologies ◽  
Female Infertility ◽  
Global Risk ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Genomic Imprints

Abstract Background Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013–2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. Results Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13–1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43–2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06–1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. Conclusions This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

scholarly journals Structure-based redesigning of pentoxifylline analogs against selective phosphodiesterases to modulate sperm functional competence for assisted reproductive technologies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mutyala Satish ◽  
Sandhya Kumari ◽  
Waghela Deeksha ◽  
Suman Abhishek ◽  
Kulhar Nitin ◽  
...  
Keyword(s):  
Sperm Motility ◽  
In Silico ◽  
Assisted Reproductive Technologies ◽  
Ex Vivo ◽  
Binding Free Energy ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Dna Integrity ◽  
Binding Studies

AbstractPhosphodiesterase (PDE) inhibitors, such as pentoxifylline (PTX), are used as pharmacological agents to enhance sperm motility in assisted reproductive technology (ART), mainly to aid the selection of viable sperm in asthenozoospermic ejaculates and testicular spermatozoa, prior to intracytoplasmic sperm injection (ICSI). However, PTX is reported to induce premature acrosome reaction (AR) and, exert toxic effects on oocyte function and early embryo development. Additionally, in vitro binding studies as well as computational binding free energy (ΔGbind) suggest that PTX exhibits weak binding to sperm PDEs, indicating room for improvement. Aiming to reduce the adverse effects and to enhance the sperm motility, we designed and studied PTX analogues. Using structure-guided in silico approach and by considering the physico-chemical properties of the binding pocket of the PDEs, designed analogues of PTX. In silico assessments indicated that PTX analogues bind more tightly to PDEs and form stable complexes. Particularly, ex vivo evaluation of sperm treated with one of the PTX analogues (PTXm-1), showed comparable beneficial effect at much lower concentration—slower AR, higher DNA integrity and extended longevity of  spermatozoa and  superior embryo quality. PTXm-1 is proposed to be a better pharmacological agent for ART than PTX for sperm function enhancement.

scholarly journals Long-Term Effects Following Fresh/Vitrified Embryo Transfer Are Transmitted by Paternal Germline in a Large Size Rabbit Cohort

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1272 ◽  
Author(s):  
Ximo Garcia-Dominguez ◽  
José Salvador Vicente ◽  
María P. Viudes-de-Castro ◽  
Francisco Marco-Jiménez
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Later Life ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Embryo Cryopreservation ◽  
Long Term Effects ◽  
Adult Body Weight ◽  
Female Germline

The concept of developmental programming suggests that the early life environment influences offspring phenotype in later life, whose effects may also be manifested in further generations. Valuable pieces of evidence come from the fields applying assisted reproductive technologies (ARTs), which deprive embryos of their optimal maternal environment and were thus associated with subsequent developmental deviations. Recently, we demonstrated that the in vitro manipulations during a vitrified embryo transfer procedure incurs a cumulative and transgenerational decline in the growth performance of the resulting offspring. Here, we provide a longitudinal study to investigate whether previous developmental deviations could be indistinctly paternally or maternally transmitted using crossbred mattings. Our findings revealed that early embryo manipulations through fresh and vitrified embryo transfer incurred paternally transmissible effects over the growth pattern and adult body weight, which seemed not inheritable via the female germline. Similar inheritable effects were observed after fresh and vitrified embryo transfer, suggesting that disturbing optimal embryo development through in vitro manipulations was the principal trigger of transmissible effects, rather than embryo cryopreservation per se.

scholarly journals Comparison of Histone H3K4me3 between IVF and ICSI Technologies and between Boy and Girl Offspring

2021 ◽  
Vol 22 (16) ◽  
pp. 8574
Author(s):  
Huixia Yang ◽  
Zhi Ma ◽  
Lin Peng ◽  
Christina Kuhn ◽  
Martina Rahmeh ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Histone Modifications ◽  
Assisted Reproductive Technologies ◽  
Histone H3 ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Vital Role ◽  
Vitro Fertilization ◽  
Cord Blood Mononuclear Cell

Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications remain limited. In the current study, we carried out immunohistochemistry, chip-sequence analysis, and a series of in vitro experiments. Our results demonstrated that placentas from intra-cytoplasmic sperm injection (ICSI), but not in vitro fertilization (IVF), showed global tri-methylated-histone-H3-lysine-4 (H3K4me3) alteration compared to those from natural conception. However, for acetylated-histone-H3-lysine-9 (H3K9ac) and acetylated-histone-H3-lysine-27 (H3K27ac), no significant differences between groups could be found. Further, sex -stratified analysis found that, compared with the same-gender newborn cord blood mononuclear cell (CBMC) from natural conceptions, CBMC from ICSI-boys presented more genes with differentially enriched H3K4me3 (n = 198) than those from ICSI-girls (n = 79), IVF-girls (n = 5), and IVF-boys (n = 2). We also found that varying oxygen conditions, RNA polymerase II subunit A (Polr2A), and lysine demethylase 5A (KDM5A) regulated H3K4me3. These findings revealed a difference between IVF and ICSI and a difference between boys and girls in H3K4me3 modification, providing greater insight into ART-associated epigenetic alteration.

Impacts of and interactions between environmental stress and epigenetic programming during early embryo development

2015 ◽  
Vol 27 (8) ◽  
pp. 1125 ◽  
Author(s):  
Michael J. Bertoldo ◽  
Yann Locatelli ◽  
Christopher O'Neill ◽  
Pascal Mermillod
Keyword(s):  
Embryo Development ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Culture Conditions ◽  
Early Embryo ◽  
Signalling Pathways ◽  
Epigenetic Programming ◽  
Altered Gene ◽  
Vitro Development

The processes of assisted reproductive technologies (ART) involve a variety of interventions that impact on the oocyte and embryo. Critically, these interventions cause considerable stress and coincide with important imprinting events throughout gametogenesis, fertilisation and early embryonic development. It is now accepted that the IVM and in vitro development of gametes and embryos can perturb the natural course of development to varying degrees of severity. Altered gene expression and, more recently, imprinting disorders relating to ART have become a focused area of research. Although various hypotheses have been put forward, most research has been observational, with little attempt to discover the mechanisms and periods of sensitivity during embryo development that are influenced by the culture conditions following fertilisation. The embryo possesses innate survival factor signalling pathways, yet when an embryo is placed in culture, this signalling in response to in vitro stress becomes critically important in mitigating the effects of stresses caused by the in vitro environment. It is apparent that not all embryos possess this ability to adequately adapt to the stresses experienced in vitro, most probably due to an inadequate oocyte. It is speculated that it is important that embryos use their survival signalling mechanisms to maintain normal epigenetic programming. The seeming redundancy in the function of various survival signalling pathways would support this notion. Any invasion into the natural, highly orchestrated and dynamic process of sexual reproduction could perturb the normal progression of epigenetic programming. Therefore the source of gametes and the subsequent culture conditions of gametes and embryos are critically important and require careful attention. It is the aim of this review to highlight avenues of research to elucidate the effects of stress and the relationship with epigenetic programming. The short- and long-term health and viability of human and animal embryos derived in vitro will also be discussed.

scholarly journals Future developments in assisted reproduction in humans

Reproduction ◽  
2002 ◽  
pp. 171-183 ◽  
Author(s):  
K Hardy ◽  
C Wright ◽  
S Rice ◽  
M Tachataki ◽  
R Roberts ◽  
...  
Keyword(s):  
Assisted Reproduction ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Embryo Biopsy ◽  
Screening Methods ◽  
Success Rates ◽  
Aneuploidy Screening ◽  
Vitro Fertilization

The advent of human in vitro fertilization (IVF) over 30 years ago has made the oocyte and preimplantation embryo uniquely accessible. This accessibility has given rise to new micromanipulation techniques, such as intracytoplasmic sperm injection for treatment of male infertility, as well as embryo biopsy for preimplantation diagnosis of both genetic disease and aneuploidy, a major cause of early embryo demise and miscarriage. In the UK, average pregnancy rates after IVF and embryo transfer are < 25%, even after transfer of several embryos. Unfortunately, a third of these pregnancies involve multiple gestations. Research is currently focusing on methods to improve IVF success rates while reducing twin and triplet pregnancies and their associated increased morbidity and mortality. One approach is to develop screening methods to identify the most viable embryos, so that transfer of fewer healthy embryos will result in a higher proportion of singleton pregnancies. Screening methods include optimizing culture conditions for prolonged culture and selection of viable blastocysts for transfer, or embryo biopsy and aneuploidy screening. Assisted reproduction is also increasingly important in other branches of medicine: survival rates for cancer sufferers are improving continually and there is now a significant need for approaches to preserve fertility after sterilizing chemo-and radiotherapy treatment. Techniques for cryopreserving male and female gametes or gonadal tissue are being developed, although systems to grow and mature these gametes are in their infancy. Finally, there are also concerns regarding the safety of these new assisted reproductive technologies.

207 Female Reproductive Fluids and Epigenetics

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 114-114
Author(s):  
Sebastian Canovas ◽  
Raquel Romar ◽  
Pilar Coy
Keyword(s):  
Assisted Reproductive Technologies ◽  
Culture Media ◽  
Morphological Changes ◽  
Adult Life ◽  
Specific Effect ◽  
Reproductive Technologies ◽  
Early Embryo ◽  
Vitro Fertilization

Abstract Physiological fertilization, and early embryo development, involves dramatic transcriptomic, epigenetic and morphological changes in a short temporal window. During this period gametes and early embryos are surrounded by reproductive fluids (oviductal and uterine), which contain nutrients, growth factors, hormones and extracellular vesicles acting as carriers of DNA, RNA, proteins and other factors with putative roles in intercellular communication. Under in vitro conditions, and in the absence of these fluids, embryos derived from Assisted Reproductive Technologies (ART) reveal transcriptional and epigenetic differences compared with in vivo embryos, which could result in long-term phenotypic consequences in adult life. Therefore, reproductive fluids supplementation in the culture medium offers an alternative to imitate physiological conditions and decrease these consequences. In vitro, oviductal fluid (OF) can modulate capacitation-associated events and sperm-zona pellucida interactions and contribute to the control of polyspermy in pigs. The use of in vitro fertilization media supplemented with reproductive fluids (Natur-IVF) improves embryo quality and blastocysts hatching ability. Moreover, Natur-IVF embryos show expression and methylation patterns closer to in vivo blastocysts. In cows, supplementation of culture media with reproductive fluids, or some isolated factors, improves blastocyst rate and survival after embryo transfer, and reverses the expression of some altered genes. However, considering the complexity of the oviductal and uterine fluids, it seems difficult that the use of just a few factors in isolation can reverse all undesired consequences of the IVP. On the other hand, sex-specific embryonic plasticity, as a consequence of the oviductal regulatory signals, have been proposed. Thus, we have analysed the sex-specific effect of supplementation with reproductive fluids in bovine embryos and data reveal sex-dependent impact in DNA methylation. All these results confirm that developmental programme can be modulated by reproductive fluids and it shows sex-specific effects. This strategy allows the possibility of minimizing undesired in vitro derived consequences.

Thickness of endometrium: predictor of the effectiveness of IVF/ICSI programs (literature review)

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 113-116
Author(s):  
L A Bagdasaryan ◽  
I E Korneyeva
Keyword(s):  
Assisted Reproductive Technologies ◽  
Endometrial Thickness ◽  
Molecular Genetic ◽  
Uterine Cavity ◽  
Reproductive Technologies ◽  
Genetic Characteristics ◽  
Vitro Fertilization ◽  
Need To Evaluate ◽  
The Relationship

The aim of the study is to systematically analyze the data available in the modern literature on the relationship between endometrial thickness and the frequency of pregnancy in the program of assisted reproductive technologies (ART). Materials and methods. The review includes data from foreign and domestic articles found in PubMed on this topic. Results. The article presents data on the relationship between the thickness of the endometrium and the frequency of pregnancy in ART programs. The greatest number of studies is devoted to the evaluation of the relationship between the thickness of the endometrium and the frequency of pregnancy on the day of the ovulation trigger. Data are presented on the existence of a correlation between the thickness of the endometrium measured on the day of the ovulation trigger and the frequency of clinical pregnancy, as well as data on the need to evaluate the structure of the endometrium and the state of subendometric blood flow. The importance of multilayered (three-layered) endometrium as a prognostic marker of success in in vitro fertilization/intracytoplasmic sperm injection programs in the ovum is emphasized. The conclusion. The thickness of the endometrium can not be used as an argument for canceling the cycle or abolishing embryo transfer to the uterine cavity. Further studies in this direction are needed with a study of the morphological and molecular genetic characteristics of the endometrium, which in the future will allow us to evaluate the relationship between the thickness of the endometrium and the probability of pregnancy.

Legal restrictions on pre-implantation genetic diagnostics in the framework of in vitro fertilization procedure: foreign experience and Russian perspective

2019 ◽  
Author(s):  
N.A. Altinnik , S.S. Zenin , V.V. Komarova et all
Keyword(s):  
In Vitro Fertilization ◽  
Assisted Reproductive Technologies ◽  
Genetic Diseases ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Legal Regulation ◽  
Genetic Diagnostics ◽  
Vitro Fertilization ◽  
Medical Indications

The article discusses the factors that determine the content of the legal limitations of pre-implantation genetic diagnosis in the framework of the in vitro fertilization procedure, taking into account international experience and modern domestic regulatory legal regulation of the field of assisted reproductive technologies. The authors substantiates the conclusion that it is necessary to legislate a list of medical indications for preimplantation genetic diagnosis, as well as the categories of hereditary or other genetic diseases diagnosed in the framework of this procedure.

scholarly journals Prevalence of pathogenic copy number variants among children conceived by donor oocyte

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra Monfort ◽  
Carmen Orellana ◽  
Silvestre Oltra ◽  
Mónica Rosello ◽  
Alfonso Caro-Llopis ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Copy Number ◽  
Assisted Reproductive Technologies ◽  
Copy Number Variants ◽  
Reproductive Technologies ◽  
Significant Excess ◽  
Vitro Fertilization ◽  
Donor Oocyte ◽  
Increased Risk

AbstractDevelopment of assisted reproductive technologies to address infertility has favored the birth of many children in the last years. The majority of children born with these treatments are healthy, but some concerns remain on the safety of these medical procedures. We have retrospectively analyzed both the fertilization method and the microarray results in all those children born between 2010 and 2019 with multiple congenital anomalies, developmental delay and/or autistic spectrum disorder (n = 486) referred for array study in our center. This analysis showed a significant excess of pathogenic copy number variants among those patients conceived after in vitro fertilization with donor oocyte with respect to those patients conceived by natural fertilization (p = 0.0001). On the other hand, no significant excess of pathogenic copy number variants was observed among patients born by autologous oocyte in vitro fertilization. Further studies are necessary to confirm these results and in order to identify the factors that may contribute to an increased risk of genomic rearrangements, as well as consider the screening for genomic alterations after oocyte donation in prenatal diagnosis.

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