Role of the mitochondrial genome in assisted reproductive technologies and embryonic stem cell-based therapeutic cloning

2004 ◽  
Vol 16 (7) ◽  
pp. 743 ◽  
Author(s):  
Carol A. Brenner ◽  
H. Michael Kubisch ◽  
Kenneth E. Pierce
Keyword(s):  
Nuclear Transfer ◽  
Assisted Reproductive Technologies ◽  
Embryonic Stem ◽  
Direct Consequence ◽  
Reproductive Technologies ◽  
Embryonic Cell ◽  
Therapeutic Cloning ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Heteroplasmy ◽  
Invasive Techniques

Mitochondria play a pivotal role in cellular metabolism and are important determinants of embryonic development. Mitochondrial function and biogenesis rely on an intricate coordination of regulation and expression of nuclear and mitochondrial genes. For example, several nucleus-derived transcription factors, such as mitochondrial transcription factor A, are required for mitochondrial DNA replication. Mitochondrial inheritance is strictly maternal while paternally-derived mitochondria are selectively eliminated during early embryonic cell divisions. However, there are reports from animals as well as human patients that paternal mitochondria can occasionally escape elimination, which in some cases has led to severe pathologies. The resulting existence of different mitochondrial genomes within the same cell has been termed mitochondrial heteroplasmy. The increasing use of invasive techniques in assisted reproduction in humans has raised concerns that one of the outcomes of such techniques is an increase in the incidence of mitochondrial heteroplasmy. Indeed, there is evidence that heteroplasmy is a direct consequence of ooplasm transfer, a technique that was used to ‘rescue’ oocytes from older women by injecting ooplasm from young oocytes. Mitochondria from donor and recipient were found in varying proportions in resulting children. Heteroplasmy is also a byproduct of nuclear transfer, as has been shown in studies on cloned sheep, cattle and monkeys. As therapeutic cloning will depend on nuclear transfer into oocytes and the subsequent generation of embryonic stem cells from resulting blastocysts, the prospect of mitochondrial heteroplasmy and its potential problems necessitate further studies in this area.

scholarly journals Generation of monogenetic cattle by different techniques of embryonic cell and somatic cell cloning - their application to biotechnological, agricultural, nutritional, biomedical and transgenic research

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Maria Skrzyszowska ◽  
Marcin Samiec
Keyword(s):  
Somatic Cell ◽  
Nuclear Transfer ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Embryonic Cell ◽  
Cell Cloning ◽  
Genetic Rescue ◽  
The Family ◽  
Current Article

AbstractThe development of effective approaches for not only the in vitro maturation (IVM) of heifer/cow oocytes and their extracorporeal fertilization (IVF) but also the non-surgical collection and transfer of bovine embryos has given rise to optimizing comprehensive in vitro embryo production (IVP) technology and improving other assisted reproductive technologies (ARTs), such as cattle cloning by embryo bisection, embryonic cell nuclear transfer (ECNT) and somatic cell nuclear transfer (SCNT). The primary goal of the present paper is to demonstrate the progress and achievements in the strategies utilized for embryonic cell cloning and somatic cell cloning in cattle. Moreover, the current article is focused on recognizing and identifying the suitability and reliability of bovine cloning techniques for nutritional biotechnology, agri-food and biopharmaceutical industry, biomedical and transgenic research and for the genetic rescue of endangered or extinct breeds and species of domesticated or wild-living artiodactyl mammals (even-toed ungulates) originating from the family Bovidae.

Two Novel Cases of Autosomal Translocations in the Horse: Warmblood Family Segregating t(4;30) and a Cloned Arabian with a de novo t(12;25)

2020 ◽  
Vol 160 (11-12) ◽  
pp. 688-697
Author(s):  
Sharmila Ghosh ◽  
Candice F. Carden ◽  
Rytis Juras ◽  
Mayra N. Mendoza ◽  
Matthew J. Jevit ◽  
...  
Keyword(s):  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Congenital Abnormalities ◽  
Assisted Reproductive Technologies ◽  
De Novo ◽  
Reproductive Technologies ◽  
Balanced Translocation ◽  
Translocation Breakpoints ◽  
Normal Offspring ◽  
Embryonic Death

We report 2 novel autosomal translocations in the horse. In Case 1, a breeding stallion with a balanced t(4p;30) had produced normal foals and those with congenital abnormalities. Of his 9 phenotypically normal offspring, 4 had normal karyotypes, 4 had balanced t(4p;30), and 1 carried an unbalanced translocation with tertiary trisomy of 4p. We argue that unbalanced forms of t(4p;30) are more tolerated and result in viable congenital abnormalities, without causing embryonic death like all other known equine autosomal translocations. In Case 2, two stallions produced by somatic cell nuclear transfer from the same donor were karyotyped because of fertility issues. A balanced translocation t(12q;25) was found in one, but not in the other clone. The findings underscore the importance of routine cytogenetic screening of breeding animals and animals produced by assisted reproductive technologies. These cases will contribute to molecular studies of translocation breakpoints and their genetic consequences in the horse.

98 BLASTOCYST DEVELOPMENT RATE OF CLONED CAT EMBRYOS USING SERIAL CLONING

2007 ◽  
Vol 19 (1) ◽  
pp. 166
Author(s):  
X. J. Yin ◽  
H. S. Lee ◽  
E. G. Choi ◽  
X. F. Yu ◽  
B. H. Choi ◽  
...  
Keyword(s):  
Nuclear Transfer ◽  
Second Generation ◽  
Assisted Reproductive Technologies ◽  
Polar Body ◽  
Donor Cell ◽  
Fibroblast Cell ◽  
Cumulus Cells ◽  
Reproductive Technologies ◽  
Blastocyst Development ◽  
First Polar Body

Domestic cats are a useful research model to develop assisted reproductive technologies for the conservation of endangered felids. Previously, we produced cloned offspring derived from somatic cell nuclear transfer of ear skin fibroblasts obtained from a deaf, odd-eyed, male Turkish Angora. The aim of this study was to assess the cloning efficiency of the fibroblasts derived from a cloned cat. Fibroblast cell lines were established from 6-mm skin biopsies taken from a deaf, odd-eyed, male Turkish Angora and his clone. The protocol for nuclear transfer was described previously (Yin et al. 2005 Reproduction 129, 245–249). Briefly, cumulus cells were removed from the ova by gently pipetting them into TCM-199 supplemented with 0.1% hyaluronidase. The denuded oocytes were then cultured in TCM-199 supplemented with 0.2 �g mL-1 demecolcine for 1 h and placed into TCM-199 containing 5 �g mL-1 cytochalasin B and 0.2 �g mL-1 demecolcine. The first polar body and protruded chromatin plate were removed with a beveled micropipette. Micromanipulation was used to place a single donor cell nucleus into the perivitelline space of enucleated ova. The ovum-cell couplets were fused and pulse activated. The activated couplets were cultured in 500 �L of CRI medium supplemented with 0.3% BSA for 2 days. The cleaved embryos were cultured in CRII medium supplemented with 10% FBS for 5 days. The cleavage and blastocyst development rates were 38.5% and 3.5% for second generation cloned embryos. A total of 310 second generation cloned embryos were transplanted to 9 surrogates, and 2 pregnancies at 30 days were determined by ultrasonography. One pregnancy was aborted at 40 days of gestation; the second pregnancy continued. These results indicate that the serial cloning of a cat can be generated efficiently up until pregnancy. This work was supported by KOSEF (grant #M10525010001-05N2501-00110).

Nuclear transfer and oocyte cryopreservation

2009 ◽  
Vol 21 (1) ◽  
pp. 37 ◽  
Author(s):  
Ching-Chien Chang ◽  
Li-Ying Sung ◽  
Tomokazu Amano ◽  
X. Cindy Tian ◽  
Xiangzhong Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Regenerative Medicine ◽  
Nuclear Transfer ◽  
Embryonic Stem ◽  
Present Review ◽  
Oocyte Cryopreservation ◽  
Patient Specific ◽  
Therapeutic Cloning ◽  
Human Oocytes

Somatic cells can be reprogrammed to a totipotent state through nuclear transfer or cloning, because it has been demonstrated that the oocyte has the ability to reprogramme an adult nucleus into an embryonic state that can initiate the development of a new organism. Therapeutic cloning, whereby nuclear transfer is used to derive patient-specific embryonic stem cells, embraces an entire new opportunity for regenerative medicine. However, a key obstacle for human therapeutic cloning is that the source of fresh human oocytes is extremely limited. In the present review, we propose prospective sources of human oocytes by using oocyte cryopreservation, such as an oocyte bank and immature oocytes. We also address some potential issues associated with nuclear transfer when using cryopreserved oocytes. In the future, if the efficacy and efficiency of cryopreserved oocytes are comparable to those of fresh oocytes in human therapeutic cloning, the use of cryopreserved oocytes would be invaluable and generate a great impact to regenerative medicine.

Response to “May a Woman Clone Herself” by Jean Chambers (CQ Vol 10, No 2)

2002 ◽  
Vol 11 (1) ◽  
pp. 83-86
Author(s):  
Timothy F. Murphy
Keyword(s):  
Nuclear Transfer ◽  
Assisted Reproductive Technologies ◽  
Married Couples ◽  
Reproductive Technologies ◽  
Same Sex ◽  
Reproductive Cloning ◽  
Same Sex Couples ◽  
Human Reproductive ◽  
Somatic Nuclear Transfer ◽  
Do So

For many commentators in bioethics and the law, safety is the fulcrum for evaluating the ethics of human reproductive cloning. Carson Strong has argued that if cloning were effective and safe it should be available to married couples who have tried to have children through various assisted reproductive technologies (ARTs) but been unable to do so. On his view, cloning should be available only as reproductive last resort. I challenged that limited use by trying to show that the arguments Strong adduces in favor of reproductive somatic nuclear transfer (SNT) for married couples extend to same-sex couples as well, who face a different kind of infertility. I also went on to argue that his justifications would in fact extend the legitimate use of SNT to any couples regardless of whether they had fertility difficulties or not.

scholarly journals Human therapeutic cloning, pitfalls and lack luster because of rapid developments in induced pluripotent stem cell technology

2014 ◽  
Vol 8 (1) ◽  
pp. 5-10
Author(s):  
Song Hua ◽  
Henry Chung ◽  
Kuldip Sidhu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Somatic Cell ◽  
Pluripotent Stem Cells ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Embryonic Stem ◽  
Therapeutic Cloning ◽  
Induced Pluripotent

AbstractBackground: Therapeutic cloning is the combination of somatic cell nuclear transfer (SCNT) and embryonic stem cell (ES) techniques to create specific ES cells that match those of a patient. Because ES cells derived by nuclear transfer (SCNT ES cells) are genetically identical to the donor, it will not generate rejection by the host’s immune system and thus therapeutically may be more acceptable. Induced pluripotent stem cells (iPS) are a type of pluripotent stem cell artificially derived from an adult somatic cell by inducing a forced expression of a set of specific pluripotent genes. In the past few years, rapid progress in reprogramming and iPS technology has been made, and it seems to shadow any progress made in SCNT programs.Objective: This review compares the application perspective of SCNT with that of iPS in regenerative medicine.Methods:We conducted a literature search using the MEDLINE (PubMed), Wiley InterScience, Springer, EBSCO, and Annual Reviews databases using the keywords “iPS”, “ES”, “SCNT” “induced pluripotent stem cells”, “embryonic stem cells”, “therapeutic cloning”, “regenerative medicine”, and “somatic cell nuclear transfer”. Only articles published in English were included in this review.Results: These two methods both have advantages and disadvantages. Nevertheless, by using SCNT to generate patient-specific cell lines, it eliminates complications by avoiding the use of viral vectors during iPS generation. Success in in vitro matured eggs from aged women and even differentiation of oocytes from germ stem cells will further enhance the application of SCNT in regenerative medicine.Conclusion: Human SCNT may be an appropriate mean of generating patient stem cell lines for clinical therapy in the near future.

Livestock in biomedical research: history, current status and future prospective

2016 ◽  
Vol 28 (2) ◽  
pp. 112 ◽  
Author(s):  
Irina A. Polejaeva ◽  
Heloisa M. Rutigliano ◽  
Kevin D. Wells
Keyword(s):  
Genome Sequence ◽  
Biomedical Research ◽  
Assisted Reproductive Technologies ◽  
Sequence Data ◽  
Embryonic Stem ◽  
Reproductive Technologies ◽  
Farm Animals ◽  
Current Status ◽  
Large Animal ◽  
Large Animal Models

Livestock models have contributed significantly to biomedical and surgical advances. Their contribution is particularly prominent in the areas of physiology and assisted reproductive technologies, including understanding developmental processes and disorders, from ancient to modern times. Over the past 25 years, biomedical research that traditionally embraced a diverse species approach shifted to a small number of model species (e.g. mice and rats). The initial reasons for focusing the main efforts on the mouse were the availability of murine embryonic stem cells (ESCs) and genome sequence data. This powerful combination allowed for precise manipulation of the mouse genome (knockouts, knockins, transcriptional switches etc.) leading to ground-breaking discoveries on gene functions and regulation, and their role in health and disease. Despite the enormous contribution to biomedical research, mouse models have some major limitations. Their substantial differences compared with humans in body and organ size, lifespan and inbreeding result in pronounced metabolic, physiological and behavioural differences. Comparative studies of strategically chosen domestic species can complement mouse research and yield more rigorous findings. Because genome sequence and gene manipulation tools are now available for farm animals (cattle, pigs, sheep and goats), a larger number of livestock genetically engineered (GE) models will be accessible for biomedical research. This paper discusses the use of cattle, goats, sheep and pigs in biomedical research, provides an overview of transgenic technology in farm animals and highlights some of the beneficial characteristics of large animal models of human disease compared with the mouse. In addition, status and origin of current regulation of GE biomedical models is also reviewed.

Embryonic stem cells in companion animals (horses, dogs and cats): present status and future prospects

2007 ◽  
Vol 19 (6) ◽  
pp. 740 ◽  
Author(s):  
R. Tayfur Tecirlioglu ◽  
Alan O. Trounson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Nuclear Transfer ◽  
Companion Animals ◽  
Embryonic Stem ◽  
Reproductive Technologies ◽  
Specific Cell ◽  
Economic Implications ◽  
Cell Therapies

Reproductive technologies have made impressive advances since the 1950s owing to the development of new and innovative technologies. Most of these advances were driven largely by commercial opportunities and the potential improvement of farm livestock production and human health. Companion animals live long and healthy lives and the greatest expense for pet owners are services related to veterinary care and healthcare products. The recent development of embryonic stem cell and nuclear transfer technology in primates and mice has enabled the production of individual specific embryonic stem cell lines in a number of species for potential cell-replacement therapy. Stem cell technology is a fast-developing area in companion animals because many of the diseases and musculoskeletal injuries of cats, dogs and horses are similar to those in humans. Nuclear transfer-derived stem cells may also be selected and directed into differentiation pathways leading to the production of specific cell types, tissues and, eventually, even organs for research and transplantaton. Furthermore, investigations into the treatment of inherited or acquired pathologies have been performed mainly in mice. However, mouse models do not always faithfully represent the human disease. Naturally occurring diseases in companion animals can be more ideal as disease models of human genetic and acquired diseases and could help to define the potential therapeutic efficiency and safety of stem cell therapies. In the present review, we focus on the economic implications of companion animals in society, as well as recent biotechnological progress that has been made in horse, dog and cat embryonic stem cell derivation.

32 CLONING OF ELITE QUARANTINE SNIFFING DOG BY SOMATIC CELL NUCLEAR TRANSFER

2013 ◽  
Vol 25 (1) ◽  
pp. 164
Author(s):  
H. J. Oh ◽  
M. J. Kim ◽  
G. A. Kim ◽  
J. Choi ◽  
E. J. Park ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Donor Cells ◽  
Wide Range ◽  
Sound Sensitivity

Somatic cell nuclear transfer (SCNT) in assisted reproductive technologies has been considered for the conservation of valuable or endangered animals. Dogs that were originally bred for hunting, such as beagles, have an exceptional ability to detect a particular smell from many others. For that reason, the beagles have been used to detect quarantine risk items from a wide range of goods in assorted luggage without scaring or disrupting the passengers. Though very useful and highly in need, elite quarantine sniffing beagles with excellent abilities are rare; much time, effort, and money are required in producing them. Here, we have applied SCNT for propagation of elite quarantine sniffing dogs to save time and economic burden. Ear fibroblasts from a 10-year-old adult male elite quarantine sniffing beagle were isolated and cultured in vitro as donor cells. For SCNT, in vivo-matured oocytes, obtained by flushing the uterine tubes of oocyte donors (mixed breed), were used. The oocytes were enucleated, microinjected with donor cells, fused by electrical stimulation, and activated chemically. Reconstructed oocytes were surgically transferred into the uterine tube of naturally synchronous recipient females. A total of 212 activated cloned embryos were transferred into 12 female recipient dogs and 4 recipients became pregnant. The 4 pregnant recipients delivered 4 pups through caesarean section or natural delivery, but 1 died right after birth and did not show an abnormality. Other live puppies exhibited normal phenotypes; their appearance was similar to that of the donor dog. All cloned pups were genetically identical to the donor dog and their mitochondrial DNA was from their oocyte donor dogs. When the cloned pups were 16 weeks old, we conducted a Volhard test, which is commonly used to describe the following puppy aptitudes: social attraction, following, restraint, social dominance, elevation dominance, retrieving, touch sensitivity, sound sensitivity, and sight sensitivity. Dog behavior data on differences in transcript abundance were analyzed by a general linear mixed model. The 3 cloned pups showed similar behavioral tendencies. The present study demonstrates that NT technique using donor cell derived from 1 elite quarantine sniffing dog is useful to produce a large number of quarantine sniffing dogs. This study was supported by RDA (no. PJ0089752012), RNL Bio (no. 550-20120006), IPET (no. 311062-04-1-SB010), Research Institute for Veterinary Science, Nestlé Purina Korea, and TS Corporation.

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