scholarly journals Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1043 ◽  
Author(s):  
Ximo Garcia-Dominguez ◽  
Francisco Marco-Jiménez ◽  
David S. Peñaranda ◽  
José Salvador Vicente
Keyword(s):  
Growth Performance ◽  
Embryo Transfer ◽  
Developmental Plasticity ◽  
Assisted Reproductive Technologies ◽  
Rabbit Model ◽  
Reproductive Technologies ◽  
Long Term Effects ◽  
Mammal Species

Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.

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 Long-term phenotypic effects following vitrified-thawed embryo transfer in a rabbit model

2018 ◽  
Author(s):  
Ximo Garcia-Dominguez ◽  
David. S. Peñaranda ◽  
Guillem Estruch ◽  
José Blanca ◽  
Victor García-Carpintero ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Rabbit Model ◽  
Reproductive Technologies ◽  
Zinc Homeostasis ◽  
Differentially Expressed ◽  
Heart Weight ◽  
In Vitro Fertilisation ◽  
Hepatic Tissue

AbstractSince the first human was conceived through in vitro fertilisation in 1978, over 6.5 million babies have been born by assisted reproductive technologies (ARTs). Although most ART babies and children seem healthy, in recent years several studies have evidenced a potential impact of ARTs on long-term development and health. Herein, we have developed an animal model to determine whether vitrified embryo transfer procedure induces phenotypic changes over the growth performance and in the complementary transcriptomic and proteomic analyses at hepatic level. To this end, 2 populations were developed; vitrified embryos transferred to the surrogate mothers (VT) and naturally conceived animals (NC). After delivery, animals were weighed weekly from 1 to 20 weeks of age. In adulthood, animals were euthanized and organs were harvested and weighed. After that, liver tissue was used to identify changes in the transcriptomic and proteomic profile. At adulthood, VT group showed significant lower body, liver and heart weight. After functional analysis of RNA-Seq data, a subset of 96 differentially expressed transcripts in VT animal were related to alteration in zinc homeostasis, lipid metabolism, and hepatic immune pathways. After proteomic analysis, a subset of 76 differentially expressed proteins also revealed some disturbed metabolic pathways related with the lipid and glycan metabolism, and an impaired oxidative metabolism related to ATP synthesis in the mitochondria. Current findings suggest that progeny derived after transfer of vitrified embryos have long-term consequences on growth rate and vital organs weights in adulthood, correlated with molecular signatures at transcriptomic and proteomic level of hepatic tissue.

scholarly journals Effect of Embryo Vitrification on the Steroid Biosynthesis of Liver Tissue in Rabbit Offspring

2020 ◽  
Vol 21 (22) ◽  
pp. 8642
Author(s):  
Francisco Marco-Jiménez ◽  
Ximo Garcia-Dominguez ◽  
Marta Domínguez-Martínez ◽  
María Pilar Viudes-de-Castro ◽  
Gianfranco Diretto ◽  
...  
Keyword(s):  
Liver Function ◽  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Preimplantation Embryo ◽  
Rabbit Model ◽  
Reproductive Technologies ◽  
Long Term Outcomes ◽  
Steroid Biosynthesis ◽  
Foetal Life

Preimplantation embryo manipulations during standard assisted reproductive technologies (ART) have significant repercussions on offspring. However, few studies to date have investigated the potential long-term outcomes associated with the vitrification procedure. Here, we performed an experiment to unravel the particular effects related to stress induced by embryo transfer and vitrification techniques on offspring phenotype from the foetal period through to prepuberal age, using a rabbit model. In addition, the focus was extended to the liver function at prepuberal age. We showed that, compared to naturally conceived animals (NC), offspring derived after embryo exposure to the transfer procedure (FT) or cryopreservation-transfer procedure (VT) exhibited variation in growth and body weight from foetal life to prepuberal age. Strikingly, we found a nonlinear relationship between FT and VT stressors, most of which were already present in the FT animals. Furthermore, we displayed evidence of variation in liver function at prepuberal age, most of which occurred in both FT and VT animals. The present major novel finding includes a significant alteration of the steroid biosynthesis profile. In summary, here we provide that embryonic manipulation during the vitrification process is linked with embryo phenotypic adaptation detected from foetal life to prepuberal age and suggests that this phenotypic variation may be associated, to a great extent, with the effect of embryo transfer.

scholarly journals Assessing the epigenetic risks of assisted reproductive technologies: a way forward

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 217-222 ◽  
Author(s):  
Federica Zacchini ◽  
Silvestre Sampino ◽  
Adrian M. Stankiewicz ◽  
Thomas Haaf ◽  
Grazyna E. Ptak
Keyword(s):  
Assisted Reproductive Technologies ◽  
Safety Evaluation ◽  
Reproductive Technologies ◽  
Long Term Effects ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Health And Disease ◽  
Civilization Disease

Since the birth of the first baby conceived by in vitro fertilization (IVF), assisted reproductive technologies (ART) have been constantly evolving to accomodate needs of a growing number of infertile couples. Rapidly developing ART procedures are directly applied for human infertility treatment without prior long-term safety evaluation. Although the majority of ART babies are healthy at birth, a comprehensive assessment of the long-term risks associated with ART is still lacking. An increased risk of epigenetic errors has been associated with the use of ART, which may contribute to the onset of civilization disease later in adolescence/adulthood and/or in subsequent generations. Therefore, our investigations should not focus on (or be limited to) the occurrence of a few very rare imprinting disorders in ART children, which might be associated with parental age and/or the use of ART, but on the possibly increased disease susceptibilities later in life and their potential transmission to the subsequent generations. Retrospective studies do not offer exhaustive information on long-term consequences of ART. Animal models are useful tools to study long-term effects including transgenerational ones and the epigenetic risk of a given ART procedure, which could then be translated to the human context. The final goal is the establishment of common guidelines for assessing the epigenetic risk of ART in humans, which will contribute to two key objectives of the Horizon2020 programme, i.e. to improve our understanding of the causes and mechanisms underlying health and disease, and to improve our ability to monitor health and prevent/manage disease.

scholarly journals Epigenetic Effects of Assisted Reproductive Technology in Human Offspring

2019 ◽  
Author(s):  
Wei Chen ◽  
Yong Peng ◽  
Xinyi Ma ◽  
Siming Kong ◽  
Shuangyan Tang ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Adult Life ◽  
Reproductive Technologies ◽  
Fresh Embryo Transfer ◽  
Vitro Fertilization ◽  
Nuclear Families ◽  
Genome Wide ◽  
Parental Background

AbstractThe births of more than 8 million infants have been enabled globally through assisted reproductive technologies (ARTs), including conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with either fresh embryo transfer (ET) or frozen embryo transfer (FET). However, the potential for elevated risks of ART-related disorders persists in adult life, and the underlying epigenetic mechanisms are largely uncharacterized. Here, we recruited 100 nuclear families and profiled the DNA methylomes, genome-wide histone modifications and transcriptomes to clarify the inherent extra risks attributable to specific ART procedures. We discovered that IVF-ET seemed to introduce less disturbance into the infant epigenome than IVF-FET or ICSI-ET did. Furthermore, we noted approximately half of the DNA methylomic changes in ART-conceived offspring could be explained by parental background biases. Through removal of the parental effect, we confirmed that ART per se would introduce minor DNA methylation changes locally. More importantly, we found that ART-induced epigenomic alterations were highly enriched in the processes which might contribute to increased incidence of preeclampsia during pregnancy and metabolic syndrome in offspring. Overall, our study provides an epigenetic basis for the potential long-term health risks in ART-conceived offspring that reinforces the need to review all methods of human ART.

scholarly journals Efficient marmoset genome engineering by autologous embryo transfer and CRISPR/Cas9 technology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yukiko Abe ◽  
Harumi Nakao ◽  
Motoki Goto ◽  
Moe Tamano ◽  
Michinori Koebis ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Genome Engineering ◽  
Assisted Reproductive Technologies ◽  
Small Body ◽  
Common Marmoset ◽  
Reproductive Technologies ◽  
Reproductive Capacity ◽  
Primate Species ◽  
Novel Method

AbstractGenetic engineering of non-human primates, which are most closely related to humans, has been expected to generate ideal animal models for human genetic diseases. The common marmoset (Callithrix jacchus) is a non-human primate species adequate for the production of genetically modified animals because of their small body size and high reproductive capacity. Autologous embryo transfer (AET) is routinely utilized in assisted reproductive technologies for humans but not for experimental animals. This study has developed a novel method for efficiently producing mutant marmosets using AET and CRISPR/Cas9 systems. The embryos were recovered from oviducts of naturally mated females, injected with Cas9/guide RNA, and transferred into the oviducts of the donors. This AET method can reduce the time for in vitro culture of embryos to less than 30 min. This method uses an embryo donor as the recipient, thus reducing the number of animals and allowing for “Reduction” in the 3R principles of humane experimental technique. Furthermore, this method can utilize nulliparous females as well as parous females. We applied our novel method and generated the 6 marmosets carrying mutations in the fragile X mental retardation 1 (FMR1) gene using only 18 females including 14 nulliparous females.

Possibility of elimination of pathogen from Babesia infected animals by means of embryo transfer

2014 ◽  
Vol 11 (2) ◽  
pp. 36-42
Author(s):  
P Erdenetogtokh ◽  
S Ganbat ◽  
Hiroshi Suzuki
Keyword(s):  
Embryo Transfer ◽  
Assisted Reproductive Technologies ◽  
Morphological Characteristics ◽  
Reproductive Technologies ◽  
Development Stage ◽  
Babesia Microti ◽  
Control Group ◽  
Mice Model ◽  
Economic Sectors

Babesia infections occur mainly in animals, and are transmitted by ticks. The severity of the diseases varies considerably depending on the species of Babesia involved as well as the immune response of the infected animal. In Mongolia infection produced by Babesia parasites is widely spread, provoking severe damage to the agricultural and economic sectors. Currently, strategies to control and prevent the infection are inefficient. Indeed, the necessity to look for suitable and accessible strategies to obtain animals free from the infection is needed. Currently, assisted reproductive technologies (ART) are used for the improvement of productivity in livestock. Moreover, embryo transfer seams to be useful approach to obtain clean embryos obtained from infected animals. Therefore, by using a mice model (ICR) infected with Babesia microti, an alternative method to obtain animals free from infection was examined. ICR mice at 8 weeks old were challenged with 0.2 ml of 1x107 IRBC/ml by i.p injection. After infection, superovulation was induced and then embryos were obtained and washed. Then, their development stage along with their morphological characteristics were monitored. In vitro embryos obtained from uninfected mice were used as a control group. The results indicate that the infection does not have any influence on pre-implantation embryonic development and morphological characteristics. Thus, we suggest that embryos obtained from infected animals might be useful for embryo transfer in order to improve productivity of livestock and reduce the risk of congenital infection. In summary, ART such as embryo transfer might be an useful technique in countries where Babesiosis is an endemic disease. DOI: http://dx.doi.org/10.5564/mjas.v11i2.214 Mongolian Journal of Agricultural Sciences Vol.11(2) 2013 pp.36-42

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 Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging—A Study of New Molecular Markers

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1265
Author(s):  
Błażej Chermuła ◽  
Wiesława Kranc ◽  
Karol Jopek ◽  
Joanna Budna-Tukan ◽  
Greg Hutchings ◽  
...  
Keyword(s):  
Cell Death ◽  
In Vitro Culture ◽  
Expression Analysis ◽  
Assisted Reproductive Technologies ◽  
Cumulus Cells ◽  
Reproductive Technologies ◽  
Oocyte Quality ◽  
Genetic Profile

In the ovarian follicle, maturation of the oocyte increases in the presence of somatic cells called cumulus cells (CCs). These cells form a direct barrier between the oocyte and external environment. Thanks to bidirectional communication, they have a direct impact on the oocyte, its quality and development potential. Understanding the genetic profile of CCs appears to be important in elucidating the physiology of oocytes. Long-term in vitro culture of CCs collected from patients undergoing controlled ovarian stimulation during in vitro fertilization procedure was conducted. Using microarray expression analysis, transcript levels were assessed on day 1, 7, 15, and 30 of culture. Apoptosis and aging of CCs strictly influence oocyte quality and subsequently the outcome of assisted reproductive technologies (ART). Thus, particular attention was paid to the analysis of genes involved in programmed cell death, aging, and apoptosis. Due to the detailed level of expression analysis of each of the 133 analyzed genes, three groups were selected: first with significantly decreased expression during the culture; second with the statistically lowest increase in expression; and third with the highest significant increase in expression. COL3A1, SFRP4, CTGF, HTR2B, VCAM1, TNFRSF11B genes, belonging to the third group, were identified as potential carriers of information on oocyte quality.

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