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.

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

2011 ◽  
Vol 23 (8) ◽  
pp. 990 ◽  
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).

Characterization of isolated bovine preantral follicles based on morphology, diameter and cell number

Zygote ◽  
2020 ◽  
Vol 28 (2) ◽  
pp. 154-159
Author(s):  
Juliana I. Candelaria ◽  
Anna C. Denicol
Keyword(s):  
Granulosa Cells ◽  
Developmental Stages ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Cell Number ◽  
Culture Conditions ◽  
Preantral Follicles ◽  
Secondary Stage

SummaryPreantral follicles are a potential reservoir of oocytes to be used in assisted reproductive technologies. With the increasing interest in developing techniques to grow preantral follicles in vitro, and as the bovine emerges as an appropriate model species to understand human folliculogenesis, the establishment of an accurate classification of developmental stages is needed. Classification of bovine preantral follicles has been mostly based on histological analysis and estimation models, which may not translate well to correctly characterize preantral follicles isolated from the ovary. In this study, we classified bovine preantral follicles by morphology upon isolation, determined diameter and number of granulosa cells by direct counting, and compared our results with previous studies reporting bovine preantral follicle classification. Follicles were isolated via homogenization of ovary tissue and classified into primary, early secondary and secondary stage based on morphology and number of layers of granulosa cells. Diameter was individually measured and Hoechst 33342 was used as a nuclear stain to count granulosa cells. We found that follicles classified by morphology into primary, early secondary, and secondary had different mean diameter and cell number (P < 0.01); cell number and diameter were positively correlated, as were cell density and cell number in each developmental stage (P < 0.01). Results obtained here were mostly in agreement with previous classifications based on histological sections and on isolated follicles, with some discrepancies. The present data add accuracy to classification of bovine preantral follicles that is critical to optimize culture conditions to produce developmentally competent oocytes.

Physiological, metabolic and transcriptional postnatal phenotypes ofin vitrofertilization (IVF) in the mouse

2017 ◽  
Vol 8 (4) ◽  
pp. 403-410 ◽  
Author(s):  
S. K. Feuer ◽  
P. F. Rinaudo
Keyword(s):  
Assisted Reproductive Technologies ◽  
Biological Significance ◽  
Great Majority ◽  
Reproductive Technologies ◽  
Culture Conditions ◽  
Molecular Evidence ◽  
Metabolic Dysfunction ◽  
Molecular Physiology ◽  
The Life Course

Approximately 1–4% of children today are conceived using assisted reproductive technologies (ARTs), includingin vitrofertilization (IVF). IVF is considered safe and the great majority of these children are healthy, yet there is increasing physiological and molecular evidence from animal models that ART is associated with postnatal metabolic and cardiovascular alterations. Understanding the mechanisms underlying these changes and determining whether they have biological significance is of paramount importance for optimizing the design of culture conditions and improving the health of ART children across the life course. In this review, we examine the evidence of molecular changes present in adult tissues of rodent offspring generated by preimplantation manipulation of gametes and embryos. Although embryo manipulationin vitrocan induce common transcriptional effects in the blastocyst, transcriptional and metabolomic signatures in adult IVF tissues are largely tissue-specific. However, there is pervasive evidence of oxidative stress and metabolic dysfunction, indicating a lasting effect of IVF on molecular physiology.

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

2005 ◽  
Vol 17 (3) ◽  
pp. 361 ◽  
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.

scholarly journals Deadly decisions: the role of genes regulating programmed cell death in human preimplantation embryo development

Reproduction ◽  
2004 ◽  
Vol 128 (3) ◽  
pp. 281-291 ◽  
Author(s):  
Andrea Jurisicova ◽  
Beth M Acton
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Cell Fate ◽  
Embryo Development ◽  
Preimplantation Embryo ◽  
Culture Media ◽  
Culture Conditions ◽  
Early Embryo ◽  
Preimplantation Embryo Development

Human preimplantation embryo development is prone to high rates of early embryo wastage, particularly under currentin vitroculture conditions. There are many possible underlying causes for embryo demise, including DNA damage, poor embryo metabolism and the effect of suboptimal culture media, all of which could result in an imbalance in gene expression and the failed execution of basic embryonic decisions. In view of the complex interactions involved in embryo development, a thorough understanding of these parameters is essential to improving embryo quality. An increasing body of evidence indicates that cell fate (i.e. survival/differentiation or death) is determined by the outcome of specific intracellular interactions between pro- and anti-apoptotic proteins, many of which are expressed during oocyte and preimplantation embryo development. The recent availability of mutant mice lacking expression of various genes involved in the regulation of cell survival has enabled rapid progress towards identifying those molecules that are functionally important for normal oocyte and preimplantation embryo development. In this review we will discuss the current understanding of the regulation of cell death gene expression during preimplantation embryo development, with a focus on human embryology and a discussion of animal models where appropriate.

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.

scholarly journals Effects of Progesterone on in Vitro Developmental Competence of Bovine Embryos

2020 ◽  
Vol 8 (1) ◽  
pp. 42
Author(s):  
Orhan Örnek ◽  
Yusuf Ziya Güzey
Keyword(s):  
Embryo Development ◽  
Culture Media ◽  
Early Embryo ◽  
Developmental Competence ◽  
Direct Role ◽  
Vitro Fertilization ◽  
Morula Stage ◽  
Vitro Development

Progesterone plays a key role in the establishment and maintenance of pregnancy in mammalian. Increasing levels of circulating progesterone in the post-conception period are associated with conceptus elongation and high pregnancy rates in cattle. Contradictory results are available on the direct role of progesterone in early embryo development. The objective of this study was to evaluate direct effects of progesterone on in vitro development of cattle embryos. Immature oocytes collected from slaughtered animals and cultured in the presence of different concentrations of progesterone (25, 50, 100 ng/mL) following in vitro fertilization. Cleavage rates in 25 and 50 ng/mL concentrations of progesterone were significantly higher than those in controls and 100 ng/mL. Rate of embryos that reached to the morula stage was similar in all groups. Supplementation of 25 and 50 ng/mL progesterone to the culture media significantly increased blastocyst yield while 100 ng/mL progesterone resulted in a decrease. As a conclusion, we can suggest that progesterone supplementation in in vitro culture may support embryo development at low levels.

scholarly journals Advantages of the outgrowth model for evaluating the implantation competence of blastocysts

2020 ◽  
Vol 47 (2) ◽  
pp. 85-93
Author(s):  
Jihyun Kim ◽  
Jaewang Lee ◽  
Jin Hyun Jun
Keyword(s):  
Maternal Effects ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Animal Experimentation ◽  
In Utero ◽  
Culture Conditions ◽  
Research Model ◽  
Ethical Problems ◽  
Implantation Process

The implantation process is highly complex and difficult to mimic <i>in vitro</i>, and a reliable experimental model of implantation has yet to be established. Many researchers have used embryo transfer (ET) to assess implantation potential; however, ET with pseudopregnant mice requires expert surgical skills and numerous sacrificial animals. To overcome those economic and ethical problems, several researchers have tried to use outgrowth models to evaluate the implantation potential of embryos. Many previous studies, as well as our experiments, have found significant correlations between blastocyst outgrowth <i>in vitro</i> and implantation in utero by ET. This review proposes the blastocyst outgrowth model as a possible alternative to animal experimentation involving ET in utero. In particular, the outgrowth model might be a cost- and time-effective alternative method to ET for evaluating the effectiveness of culture conditions or treatments. An advanced outgrowth model and further culture of outgrowth embryos could provide a subtle research model of peri- and postimplantation development, excluding maternal effects, and thereby could facilitate progress in assisted reproductive technologies. Recently, we found that outgrowth embryos secreted extracellular vesicles containing specific microRNAs. The function of microRNAs from outgrowth embryos should be elucidated in further researches.

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