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Reproductive biotechnologies can separate concepts of parenthood into genetic, gestational and social dimensions, often leading to a fragmentation of heteronormative kinship models and posing a challenge to historical methods of establishing legal and/or moral parenthood. Using fictional cases, this article will demonstrate that the issues surrounding the intersection of current and emerging reproductive biotechnologies with definitions of parenthood are already leading to confusion regarding social and legal family ties for offspring, which is only expected to increase as new technologies develop. Rather than opposing these new technologies to reassert traditional concepts of the family, however, this article will explore the opportunities that these technologies represent for re‐imagining various culturally cherished values of family‐making in a way that is inclusive of diverse genders, sexualities and cultures. It will consider IVF, gametogenesis, mitochondrial donation, surrogacy, artificial gestation, CRISPR‐Cas9 gene editing, foster care and adoption as some of many possible pathways to parenthood, including for members of the LGBTIAUQ+ community. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation. Methods MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography. Result Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator. Conclusions In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies.

Background: Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation. Methods: MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography. Result: Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p < 0.05). Western blotting revealed the significant reduction of Rab8 and p-FAK in 3-MA-treated MSCs (p < 0.05), indicating the inhibition of TNT assembly and vesicle transport. Likewise, the stimulation of autophagy increased autophagic flux and mitochondrial membrane integrity compared to 3-MA-treated MSCs. Despite these findings, protein levels of mitochondrial membrane Miro1 and 2 were unchanged after autophagy inhibition/stimulation (p > 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator. Conclusions: In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies. [ABSTRACT FROM AUTHOR]

Changes to Australian law in 2022 made Australia the second country to expressly permit the clinical use of mitochondrial donation (MD), a technology that makes heritable changes to the human genome. This paper considers these changes in the context of Australia's broader controls on human embryo use to provide insights into future regulatory responses to other emerging genetic technologies, which could be used in reproduction. [ABSTRACT FROM AUTHOR]

Changes to Australian law in 2022 made Australia the second country to expressly permit the clinical use of mitochondrial donation (MD), a technology that makes heritable changes to the human genome. This paper considers these changes in the context of Australia’s broader controls on human embryo use to provide insights into future regulatory responses to other emerging genetic technologies, which could be used in reproduction.

There seems to be a consensus that enucleated oocyte donation (EOD) should only be used to reduce the risk of having a child with mitochondrial disorders. However, this paper argues that in the initial phase in which we are at the moment, EOD should first be used to remedy infertility caused by poor oocyte quality or poor embryonic development. That learning period will allow researchers to improve their technical skills and the knowledge of the best procedure before starting on high-risk cases. Mitochondrial carryover of pathologic mtDNA is the main cause of concern for the offspring. That risk does not exist in infertility cases. The application of EOD to treat infertility should at present be performed in a clinical research setting to obtain more evidence about efficacy and safety. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA), as its name implies, is an embodiment of the mitochondrial genetic information that constitutes about 1% of the mammalian genome. It fills a vital niche in tracing matrilineality; the mtDNA is inherited solely from the mother and plays a crucial role in genealogical research. Even a single mutation in the mtDNA can have debilitating and life-altering consequences. Mothers carrying mtDNA mutations will inevitably pass it on to the future generation. Three-parent In vitro fertilization (IVF), a breakthrough technique, shows promising potential to prevent mothers with mtDNA defects from passing it on to their future generation, while also maintaining the genetic link to their posterity. In this review, I delve into the intricacies of this technique, compare and analyze the difference between maternal spindle transfer and pronuclear transfer, discuss the prospective therapeutic effects, and highlight the ethical concerns surrounding this procedure. Considering the various challenges and ethics of this contentious technique, the paper seeks to answer the rousing question – Is three-parent IVF the answer to preventing mitochondrial defects?

Ovarian cancer is characterized by early metastatic spread. This study demonstrates that carcinoma-associated mesenchymal stromal cells (CA-MSCs) enhance metastasis by increasing tumor cell heterogeneity through mitochondrial donation. CA-MSC mitochondrial donation preferentially occurs in ovarian cancer cells with low levels of mitochondria ("mito poor"). CA-MSC mitochondrial donation rescues the phenotype of mito poor cells, restoring their proliferative capacity, resistance to chemotherapy, and cellular respiration. Receipt of CA-MSC-derived mitochondria induces tumor cell transcriptional changes leading to the secretion of ANGPTL3, which enhances the proliferation of tumor cells without CA-MSC mitochondria, thus amplifying the impact of mitochondrial transfer. Donated CA-MSC mitochondrial DNA persisted in recipient tumor cells for at least 14 days. CA-MSC mitochondrial donation occurs in vivo, enhancing tumor cell heterogeneity and decreasing mouse survival. Collectively, this work identifies CA-MSC mitochondrial transfer as a critical mediator of ovarian cancer cell survival, heterogeneity, and metastasis and presents a unique therapeutic target in ovarian cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The article offers Parliamentary news brifs from Australia and discusses the Mitochondrial Donation Law Reform (Maeve's Law) Bill 2021 that amends Prohibition of Human Cloning for Reproduction Act 2002 and Freedom of Information Act 1982 and Prohibition of Human Cloning for Reproduction Act 2002. It offers views of several legislators including Julian Leeser, Kevin Andrews, and Matthew Canavan on the bill.

Mitochondrial DNA (mtDNA), as its name implies, is an embodiment of the mitochondrial genetic information that constitutes about 1% of the mammalian genome. It fills a vital niche in tracing matrilineality; the mtDNA is inherited solely from the mother and plays a crucial role in genealogical research. Even a single mutation in the mtDNA can have debilitating and life-altering consequences. Mothers carrying mtDNA mutations will inevitably pass it on to the future generation. Three-parent In vitro fertilization (IVF), a breakthrough technique, shows promising potential to prevent mothers with mtDNA defects from passing it on to their future generation, while also maintaining the genetic link to their posterity. In this review, I delve into the intricacies of this technique, compare and analyze the difference between maternal spindle transfer and pronuclear transfer, discuss the prospective therapeutic effects, and highlight the ethical concerns surrounding this procedure. Considering the various challenges and ethics of this contentious technique, the paper seeks to answer the rousing question - Is three-parent IVF the answer to preventing mitochondrial defects?. [ABSTRACT FROM AUTHOR]

Mitochondrial disorders manifest enormous genetic and clinical heterogeneity - they can appear at any age, present with various phenotypes affecting any organ, and display any mode of inheritance. What mitochondrial diseases do have in common, is impairment of respiratory chain activity, which is responsible for more than 90 % of energy production within cells. While diagnostics of mitochondrial disorders has been accelerated by introducing Next-Generation Sequencing techniques in recent years, the treatment options are still very limited. For many patients only a supportive or symptomatic therapy is available at the moment. However, decades of basic and preclinical research have uncovered potential target points and numerous compounds or interventions are now subjects of clinical trials. In this review, we focus on current and emerging therapeutic approaches towards the treatment of mitochondrial disorders. We focus on small compounds, metabolic interference, such as endurance training or ketogenic diet and also on genomic approaches. [ABSTRACT FROM AUTHOR]

Human oocytes have an abundance of mitochondria that have their own genome. Mitochondrial functions are exerted through evolutionarily-developed interactions between the nucleus and mitochondria. Since 1996, fertility clinics have practiced various types of germline mitochondrial DNA (mtDNA) modification that alter the composition of mtDNA copies in oocytes or zygotes using micromanipulation. Experimental reproductive medicine has primarily intended to treat intractable infertility and has been used to prevent the maternal transmission of a pathogenic mtDNA mutation to offspring. In some cases, it has helped parents have a healthy genetically-related child; in others, it has resulted in miscarriages, aneuploid fetuses, or developmental disorders in the offspring. Adverse events have raised ethical controversy, leading to restrictive or prohibitive policies in the USA and China. Conversely, the UK recently became the first nation to explicitly permit two types of germline mtDNA modification (termed mitochondrial donation) for the sole purpose of preventing serious mitochondrial disease in offspring. The aim of this review is three-fold: first, to reshape the medical concept and evolution of germline mtDNA modification, while revisiting 14 clinical cases. Second, to analyse the legality of mtDNA modification, focussing on 16 Western countries. Finally, to consider the ethical aspects, including permissible cases, reproductive options, use of preimplantation and prenatal testing, and the humane follow-up of resultant children. The clinical use of germline mtDNA modification will likely become legal, at least for use in preventative medicine, in some countries. However, the potential clinical, ethical, and evolutionary implications mean that caution is required when considering its wider application.

Sperm, eggs and embryos are made up of more than genes, and there are indications that changes to non‐genetic structures in these elements of the germline can also be inherited. It is, therefore, a mistake to treat phrases like 'germline inheritance' and 'genetic inheritance' as simple synonyms, and bioethical discussion should expand its focus beyond alterations to the genome when considering the ethics of germline modification. Moreover, additional research on non‐genetic inheritance draws attention to a variety of means whereby differences can be inherited in offspring generations that do not rely on differences in germline structures. Research on these diverse forms of inheritance challenges the notion that there is some special form of ethical concern that falls on germline interventions in general, and on interventions to the nuclear genome within the germline in particular. [ABSTRACT FROM AUTHOR]

The article describes the developing technologies for the production of «designer embryos» also known as genetically improved babies. The authors briefly review these technologies with a special emphasis on their medical, legal and bioethical aspects. We propose and substantiate the point of view why some of these approaches may be illegal.

Reproductive rights in South Africa have traditionally focused on the rights of individuals to avoid reproduction. However, with an increase in the use of assisted reproductive technologies (ART), there has been a shift in the focus on reproductive rights from the rights of individuals to avoid reproduction to the rights of individuals to reproduce noncoitally. With the emergence of new technologies, reproduction by noncoital means and the right to engage in these new technologies is becoming more prevalent. This raises two questions. The first question is whether such a right exists. The recent Constitutional Court decision in AB v Minister of Social Development 2017 3 BCLR 267 (CC) suggests that it does, but only if the person claiming this right is physically involved in the reproductive process. Ostensibly this excludes those who cannot contribute to the reproduction of a child. The second question raised pertains to the impact of this right on specific forms of ART, namely mitochondrial transfer, posthumous reproduction and embryo donation. While the first two forms of ART would meet the criteria set down in AB, embryo donation would not. Individuals denied access to embryo donation could thus not rely on either the right to reproductive autonomy or the right to privacy to aid them. Fortunately the existing legal framework provides some assistance to these individuals, although sadly the same legislative framework does not support the use of mitochondrial transfer and posthumous reproduction. In this respect there is incongruence between rights and legislation, which has only been exacerbated by the recent Constitutional Court decision. What is thus needed is clarity on the meaning of certain rights in respect of certain forms of ART as well as legislative reform to reflect the clarified position.

Conferences are important performative sites. Here we detail a UK science policy conference debating the novel biomedical techniques CRISPR/cas9 and mitochondrial donation. Both techniques have received significant attention from scientists and bioethicists about their clinical potential, social implications, and the prospects of genetic and germline modification. In many countries the policy debates on regulating both technologies is ongoing and operating in tandem. The UK, however, is operating in a distinct policy context in that mitochondrial donation was formally legalized under license in 2015, meaning the British CRISPR/cas9 debates occur in the light of a confirmed policy position on mitochondrial donation. Our analysis of the Progress Educational Trust 2015 annual conference ‘From Three-Person IVF to Genome Editing’ argues that this event conducted important staging work in articulating the relationship between these two technologies in the UK. These efforts constitute what we call a ‘transition performance’ that (i) enacted the successful resolution of the mitochondrial donation policy debate, (ii) performed the success of British biomedical politics, and (iii) opened the space for a public debate on CRISPR/cas9 in line with a specifically configured set of legitimacy practices. Subsequently the conference contrasts to many other conferences that fit what we term a ‘continuity performance’ that seek to assert consistency and progress through iteration. We close by articulating further applications and developments of these notions in Science and Technology Studies.

Study Question: Does an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted?Summary Answer: After hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation.What Is Known Already: Research suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods.Study Design, Size, Duration: This study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017.Participants/materials, Setting, Methods: Jurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?'Main Results and the Role Of Chance: Eleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors.Limitations, Reasons For Caution: Jurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population.Wider Implications Of the Findings: When presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation.Study Funding/competing Interest(s): This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Background The first live birth following the use of a new reproductive technique, maternal spindle transfer (MST), which is a mitochondrial replacement technique (MRT), was accomplished by dividing the execution of the MST procedure between two countries, the USA and Mexico. This was done in order to avoid US legal restrictions on this technique. Sources of data Academic articles, news articles, documents obtained through freedom of information requests, laws, regulations and national reports. Areas of agreement MRTs are new reproductive techniques that present novel ethical and legal challenges, since genetic material from three people is employed to create a child. Areas of controversy Could the first MST procedure that culminated in a live birth negatively impact reproductive medicine in Mexico? Growing points The USA and Mexico need specific and clear legislation on MRTs, in order for such techniques not to be governed by prior existing legislation on assisted reproduction that is inadequate for dealing with the new challenges that these techniques present. Areas timely for developing research There is a pressing need for work to be done on the international governance of new reproductive techniques. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial DNA (mtDNA) diseases are a group of maternally inherited genetic disorders caused by a lack of energy production. Currently, mtDNA diseases have a poor prognosis and no known cure. The chance to have unaffected offspring with a genetic link is important for the affected families, and mitochondrial replacement techniques (MRTs) allow them to do so. MRTs consist of transferring the nuclear DNA from an oocyte with pathogenic mtDNA to an enucleated donor oocyte without pathogenic mtDNA. This paper aims to determine the efficacy, associated risks, and main ethical and legal issues related to MRTs. Methods: A bibliographic review was performed on the MEDLINE and Web of Science databases, along with searches for related clinical trials and news. Results: A total of 48 publications were included for review. Five MRT procedures were identified and their efficacy was compared. Three main risks associated with MRTs were discussed, and the ethical views and legal position of MRTs were reviewed. Conclusions: MRTs are an effective approach to minimizing the risk of transmitting mtDNA diseases, but they do not remove it entirely. Global legal regulation of MRTs is required.

ARGUMENTATION STRATEGIES IN THE DEBATE ON MITOCHONDRIAL DONATION Bioethical aspects of mitochondrial donation have recently become one of the most debated issues. The growing interest in the philosophical and bioethical problems it generates has become even more visible since mitochondrial donation was legally allowed in Great Britain in 2015. In this paper we will take a closer look at the arguments employed in the debate, such as 1) argument from uncertainty closely connected with an obligation to use safe and already known alternative medical procedures; 2) the threat of losing personal identity; 3) the fear of creating a child of three parents; 4) detrimental outcome of manipulation in the human germ line. We will analyze the arguments showing that they are in fact the result of the lack of precision in employing medical terminology, the simplification of argumentation or the manifestation of ‘status quo bias’.

Abstract: The Institute of Medicine has recently endorsed arguments put forward by John Appleby calling for mandatory sex selection against female offspring in the initial trials of mitochondrial replacement techniques. In this paper I argue that, despite this endorsement, the reasons offered by Appleby for mandatory sex selection are inadequate. I further argue that plausible revisions to Appleby's arguments still fail to convincingly defend such an intrusive policy. While I remain neutral about whether intending parents making use of mitochondrial replacement techniques ought to have access to sex selection, I conclude that to date the case for mandatory sex selection has not been satisfactorily made. [ABSTRACT FROM AUTHOR]

Jurisdictions are beginning to respond to growing demands to begin the clinical use of mitochondrial donation in human embryos. This form of directed modification of human embryos is intended to prevent mitochondrial disease in future members of families with a known history of such disease. At least one child has already been born after the technique was used during his conception. The United Kingdom has legalized such use and the United States has undertaken high level reviews of the legal and ethical issues that arise from it. Other jurisdictions, such as Australia, continue to prohibit the clinical use of the technique. Using these three distinct responses, this article identifies three fundamental issues raised by the clinical use of mitochondrial donation that must be addressed by jurisdictions considering their own governance responses and analyzes the policy and regulatory contexts that impact how these issues are or will be responded to. Drawing on this analysis, the article discusses how the studied frameworks can inform future governance arrangements in other jurisdictions considering clinical mitochondrial donation. [ABSTRACT FROM AUTHOR]

Mitochondria are present in all human cells and vary in number from a few tens to many thousands. As they generate the majority of a cell's energy supply which power every part of our body, and hence, their number varies in different cells as per the energy requirement of the cell. Mitochondria have their own separate DNA, which carries total 13 genes. All of these 13 genes are involved in energy production. For normal functioning of cells, the mitochondria need to be healthy. Unhealthy mitochondria can cause severe medical disorders known as mitochondrial disease. In case of mitochondrial disease, the most commonly affected organs are the heart, kidney, skeletal muscle, and brain. The diseases related to defects in these organs are quite prevalent in the society. Majority of these mitochondrial diseases are caused by genetic defects (mutations) in the mitochondrial DNA. Unlike nuclear genes, mitochondrial DNA is inherited only from our mother. Mothers can carry abnormal mitochondria and be at risk of passing on the serious disease to their children, even if they themselves show only mild or no symptoms. Due to the complex nature of these diseases, their diagnosis and therapy are very difficult. Hence, till now, only the different methods for management of these diseases are known. However, after understanding the complexity related to the cure of these diseases, alternative methods have been developed to minimize/stop the transfer of mitochondrial diseases from mother to offspring. This latest technique is called mitochondrial replacement or "donation." In the present review, we are discussing the methodological details and issues related to the technique of mitochondrial donation. Our study is also a step toward raising awareness about mitochondrial diseases and advocating for the legalization of mitochondrial donation, a revolutionary in vitro fertilization technique. [ABSTRACT FROM AUTHOR]

News about the first baby born after a mitochondrial replacement technique (MRT; specifically maternal spindle transfer) broke on September 27, 2016 and, in a matter of hours, went global. Of special interest was the fact that the mitochondrial replacement procedure happened in Mexico. Oneof the scientists behind this world firstwas quoted as having said that he and his team went to Mexico to carry out the procedure because, inMexico, there are no rules. In this paper, we exploreMexico's rule of law in relation to mitochondrial replacement techniques and show that, in fact, certain instances ofMRTs are prohibited at the federal level and others are prohibited at the state level. According to our interpretation of the law, the scientists behind this first successful MRT procedure broke federal regulations regarding assisted fertilization research. [ABSTRACT FROM AUTHOR]

In October 2015 the UK enacted legislation to permit the clinical use of two cutting edge germline-altering, IVF-based embryonic techniques: pronuclear transfer and maternal spindle transfer (PNT and MST). The aim is to use these techniques to prevent the maternal transmission of serious mitochondrial diseases. Major claims have been made about the quality of the debates that preceded this legislation and the significance of those debates for UK decision-making on other biotechnologies, as well as for other countries considering similar legislation. In this article we conduct a systematic analysis of those UK debates and suggest that claims about their quality are over-stated. We identify, and analyse in detail, ten areas where greater clarity, depth and nuance would have produced sharper understandings of the contributions, limitations and wider social impacts of these mitochondrial interventions. We explore the implications of these additional considerations for (i) the protection of all parties involved, should the techniques transfer to clinical applications; (ii) the legitimacy of focussing on short-term gains for individuals over public health considerations, and (iii) the maintenance and improvement of public trust in medical biotechnologies. We conclude that a more measured evaluation of the content and quality of the UK debates is important and timely: such a critique provides a clearer understanding of the possible, but specific, contributions of these interventions, both in the UK and elsewhere; also, these additional insights can now inform the emerging processes of implementation, regulation and practice of mitochondrial interventions. [ABSTRACT FROM AUTHOR]

Mitochondrial donation (or mitochondrial replacement techniques, MRT) is a special form of in vitro fertilisation involving the mitochondrial DNA (mtDNA) of a third (donor) party. This technique eliminates the risk of severe mitochondrial pathologies, genetically inherited from the mother, by replacing part of her mtDNA with healthy mtDNA from another woman, the donor. This paper explores the ethical dimensions of this technique and their impact upon policy decisions. In particular, it is argued that despite the spectacular fact that a child might have three genetic sources, the bi-parental paradigm is not truly challenged. The most important issue surrounding mitochondrial donation is the fact that it involves germline modification. To this extent, approval of such a technique sets a precedent. There is a wide and traditional international consensus on prohibiting human germ-line modification, and this paper examines whether the specific procedure of mitochondrial donation falls within this logic. [ABSTRACT FROM AUTHOR]

Reproductive rights in South Africa have traditionally focused on the rights of individuals to avoid reproduction. However, with an increase in the use of assisted reproductive technologies (ART), there has been a shift in the focus on reproductive rights from the rights of individuals to avoid reproduction to the rights of individuals to reproduce noncoitally. With the emergence of new technologies, reproduction by noncoital means and the right to engage in these new technologies is becoming more prevalent. This raises two questions. The first question is whether such a right exists. The recent Constitutional Court decision in AB v Minister of Social Development 2017 3 BCLR 267 (CC) suggests that it does, but only if the person claiming this right is physically involved in the reproductive process. Ostensibly this excludes those who cannot contribute to the reproduction of a child. The second question raised pertains to the impact of this right on specific forms of ART, namely mitochondrial transfer, posthumous reproduction and embryo donation. While the first two forms of ART would meet the criteria set down in AB, embryo donation would not. Individuals denied access to embryo donation could thus not rely on either the right to reproductive autonomy or the right to privacy to aid them. Fortunately the existing legal framework provides some assistance to these individuals, although sadly the same legislative framework does not support the use of mitochondrial transfer and posthumous reproduction. In this respect there is incongruence between rights and legislation, which has only been exacerbated by the recent Constitutional Court decision. What is thus needed is clarity on the meaning of certain rights in respect of certain forms of ART as well as legislative reform to reflect the clarified position. [ABSTRACT FROM AUTHOR]

Mitochondrial replacement techniques (MRT) are intended to avoid the transmission of mitochondrial diseases from mother to child. MRT represent a potentially powerful new biomedical technology with ethical, policy, economic and social implications. Among other ethical questions raised are concerns about the possible effects on the identity of children born from MRT, their families, and the providers or donors of mitochondria. It has been suggested that MRT can influence identity (i) directly, through altering the genetic makeup and physical characteristics of the child, or (ii) indirectly through changing the child's experience of disease, and by generating novel intrafamilial relationships that shape the sense of self. In this article I consider the plausibility and ethical implications of these proposed identity effects, but I focus instead on a third way in which identity may be affected, through the mediating influence of the wider social world on MRT effects on identity. By taking a narrative approach, and examining the nature and availability of identity narratives, I conclude that while neither direct genetic nor indirect experiential effects can be excluded, social responses to MRT are more likely to have a significant and potentially damaging influence on the generation of MRT children's narratives of identity. This conclusion carries some implications for the collective moral responsibility we hold to ensure that MRT, if implemented, are practised in ethically justifiable ways. [ABSTRACT FROM AUTHOR]

Jürgen Habermas is regarded as a central bioconservative commentator in the debate on the ethics of human prenatal genetic manipulations. While his main work on this topic, The Future of Human Nature, has been widely examined in regard to his position on prenatal genetic enhancement, his arguments regarding prenatal genetic therapeutic interventions have for the most part been overlooked. In this work I do two things. First, I present the three necessary conditions that Habermas establishes for a prenatal genetic manipulation to be regarded as morally permissible. Second, I examine if mitochondrial replacement techniques meet these necessary conditions. I investigate, specifically, the moral permissibility of employing pronuclear transfer and maternal spindle transfer. I conclude that, according to a Habermasian perspective on prenatal genetic manipulation, maternal spindle transfer (without using a preselected sperm and egg) and pronuclear transfer are morally impermissible. Maternal spindle transfer is, in principle, morally permissible, but only when we have beforehand preselected a sperm and an egg for our reproductive purpose. These findings are relevant for bioconservatives, both for those who hold a Habermasian stance and for those who hold something akin to a Habermasian stance, because they answer the question: what should bioconservatives do regarding mitochondrial replacement techniques? In fact, the answer to this question does not only normatively prescribe what bioconservatives should do in terms of their personal morality, but it also points towards what kind of legislation regulating mitochondrial replacement techniques they should aim at. [ABSTRACT FROM AUTHOR]

Mitochondrial replacement techniques (MRTs), known in the popular media as 'three-parent' or 'three-person' IVFs, have the potential to enable women with mitochondrial diseases to have children who are genetically related to them but without such diseases. In the debate regarding whether MRTs should be made available, an issue that has garnered considerable attention is whether MRTs affect the characteristics of an existing individual or whether they result in the creation of a new individual, given that MRTs involve the genetic manipulation of the germline. In other words, do MRTs affect the qualitative identity or the numerical identity of the resulting child? For instance, a group of panelists on behalf of the UK Human Fertilisation and Embryology Authority (HFEA) has claimed that MRTs affect only the qualitative identity of the resulting child, while the Working Group of the Nuffield Council on Bioethics (NCOB) has argued that MRTs would create a numerically distinct individual. In this article, I shall argue that MRTs do create a new and numerically distinct individual. Since my explanation is different from the NCOB's explanation, I shall also offer reasons why my explanation is preferable to the NCOB's explanation. [ABSTRACT FROM AUTHOR]

In February 2015 the UK became the first country to legalise high-profile mitochondrial replacement techniques (MRTs), which involve the creation of offspring using genetic material from three individuals. The aim of these new cell reconstruction techniques is to prevent the transmission of maternally inherited mitochondrial disorders to biological offspring. During the UK debates, MRTs were often positioned as a straightforward and unique solution for the 'eradication' of mitochondrial disorders, enabling hundreds of women to have a healthy, biologically-related child. However, many questions regarding future applications and potential users remain. Drawing on a current qualitative study on reproductive choices in the context of mitochondrial disorders, this article illustrates how the potential limitations of MRTs have been obscured in public debates by contrasting the claims made about the future beneficiaries with insights from families affected by mitochondrial disorders and medical experts. The analysis illuminates the complex choices with which families and individuals affected by mitochondrial disorders are faced, which have thus far remained invisible. An argument is presented for improved information for the public as well as an intensification of critical empirical research around the complex and specific needs of future beneficiaries of new reproductive biotechnologies. [ABSTRACT FROM AUTHOR]

The classification of techniques used in mitochondrial donation, including their role as purported germ-line gene therapies, is far from clear. These techniques exhibit characteristics typical of a variety of classifications that have been used in both scientific and bioethics scholarship. This raises two connected questions, which we address in this paper: (i) how should we classify mitochondrial donation techniques?; and (ii) what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ-line gene therapy, are typically defined or classified. We then consider whether techniques of mitochondrial donation fit into these, whether they might do so with some refinement of these categories, or whether they require some other approach to classification. To answer the second question, we discuss the relationship between classification and several key ethical issues arising from mitochondrial donation. We conclude that the properties characteristic of mitochondrial inheritance mean that most mitochondrial donation techniques belong to a new sub-class of genetic modification, which we call 'conditionally inheritable genomic modification' (CIGM). [ABSTRACT FROM AUTHOR]

Background: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are capable of repairing wounded lung epithelial cells by donating cytoplasmic material and mitochondria. Recently, we characterized two populations of human lung-derived mesenchymal stromal cells isolated from digested parenchymal lung tissue (LT-MSCs) from healthy individuals or from lung transplant recipients' bronchoalveolar lavage fluid (BAL-MSCs). The aim of this study was to determine whether LT-MSCs and BAL-MSCs are also capable of donating cytoplasmic content and mitochondria to lung epithelial cells. Methods: Cytoplasmic and mitochondrial transfer was assessed by co-culturing BEAS2B epithelial cells with Calcein AM or Mitotracker Green FM-labelled MSCs. Transfer was then measured by flow cytometry and validated by fluorescent microscopy. Molecular inhibitors were used to determine the contribution of microtubules/tunnelling nanotubes (TNTs, cytochalasin D), gap junctions (carbenoxolone), connexin-43 (gap26) and microvesicles (dynasore). Results: F-actin microtubules/TNTs extending from BM-MSCs, LT-MSCs and BAL-MSCs to bronchial epithelial cells formed within 45 minutes of co-culturing cells. Each MSC population transferred a similar volume of cytoplasmic content to epithelial cells. Inhibiting microtubule/TNTs, gap junction formation and microvesicle endocytosis abrogated the transfer of cytoplasmic material from BM-MSCs, LT-MSCs and BAL-MSCs to epithelial cells. In contrast, blocking connexin-43 gap junction formation had no effect on cytoplasmic transfer. All MSC populations donated mitochondria to bronchial epithelial cells with similar efficiency. Mitochondrial transfer was reduced in all co-cultures after microtubule/TNT or endocytosis inhibition. Gap junction formation inhibition reduced mitochondrial transfer in BM-MSC and BAL-MSC co-cultures but had no effect on transfer in LT-MSC co-cultures. Connexin-43 inhibition did not impact mitochondrial transfer. Finally, bronchial epithelial cells were incapable of donating cytoplasmic content or mitochondria to any MSC population. Conclusion: Similar to their bone marrow counterparts, LT-MSCs and BAL-MSCs can donate cytoplasmic content and mitochondria to bronchial epithelial cells via multiple mechanisms. Given that BM-MSCs utilize these mechanisms to mediate the repair of damaged bronchial epithelial cells, both LT-MSCs and BAL-MSCs will probably function similarly. [ABSTRACT FROM AUTHOR]

Introduction or background: The UK is at the forefront of mitochondrial science and is currently the only country in the world to legalize germ-line technologies involving mitochondrial donation. However, concerns have been raised about genetic modification and the 'slippery slope' to designer babies. Sources of data: This review uses academic articles, newspaper reports and public documents. Areas of agreement: Mitochondrial donation offers women with mitochondrial disease an opportunity to have healthy, genetically related children. Areas of controversy: Key areas of disagreement include safety, the creation of three-parent babies, impact on identity, implications for society, definitions of genetic modification and reproductive choice. Growing points: The UK government legalized the techniques in March 2015. Scientific and medical communities across the world followed the developments with interest. Areas timely for developing research: It is expected that the first cohort of 'three parent' babies will be born in the UK in 2016. Their health and progress will be closely monitored. [ABSTRACT FROM AUTHOR]