Toxicant effects on mammalian oocyte mitochondria†

Primordial Germ Cells ◽

Mature Oocyte ◽

Developmental Origins ◽

Founder Population ◽

Mammalian Oocyte ◽

Transport Chain ◽

Polycyclic Aromatic ◽

Health And Disease

Abstract Oocyte mitochondria are unique organelles that establish a founder population in primordial germ cells (PGCs). As the oocyte matures in the postnatal mammalian ovary during folliculogenesis it increases exponentially in volume, and the oocyte mitochondria population proliferates to about 100 000 mitochondria per healthy, mature murine oocyte. The health of the mature oocyte and subsequent embryo is highly dependent on the oocyte mitochondria. Mitochondria are especially sensitive to toxic insults, as they are a major source of reactive oxygen species (ROS), they contain their own DNA (mtDNA) that is unprotected by histone proteins, they contain the electron transport chain that uses electron donors, including oxygen, to generate ATP, and they are important sensors for overall cellular stress. Here we review the effects that toxic insults including chemotherapeutics, toxic metals, plasticizers, pesticides, polycyclic aromatic hydrocarbons (PAHs), and ionizing radiation can have on oocyte mitochondria. This is very clearly a burgeoning field, as our understanding of oocyte mitochondria and metabolism is still relatively new, and we contend much more research is needed to understand the detrimental impacts of exposure to toxicants on oocyte mitochondria. Developing this field further can benefit our understanding of assisted reproductive technologies and the developmental origins of health and disease (DOHaD).

Assisted Reproductive Technologies and the Developmental Origins of Health and Disease

Seminars in Reproductive Medicine ◽

10.1055/s-0038-1676641 ◽

2018 ◽

Vol 36 (03/04) ◽

pp. 173-174

Author(s):

James Segars

Keyword(s):

Developmental Origins ◽

Health And Disease

Assisted Reproductive Technologies and the Developmental Origins of Human Health and Disease

Seminars in Reproductive Medicine ◽

10.1055/s-0039-1683393 ◽

2018 ◽

Vol 36 (03/04) ◽

pp. 175-176

Author(s):

Micah Hill

Keyword(s):

Human Health ◽

Developmental Origins ◽

Health And Disease

Transitioning from Infertility-Based (ART 1.0) to Elective (ART 2.0) Use of Assisted Reproductive Technologies and the DOHaD Hypothesis: Do We Need to Change Consenting?

Seminars in Reproductive Medicine ◽

10.1055/s-0038-1677526 ◽

2018 ◽

Vol 36 (03/04) ◽

pp. 204-210 ◽

Cited By ~ 1

Author(s):

Amanda Adeleye ◽

Paolo Rinaudo

Keyword(s):

Family Planning ◽

Glucose Intolerance ◽

Animal Studies ◽

Parents And Children ◽

Health And Disease ◽

Infertile Patients ◽

Art Techniques

AbstractThe use of assisted reproductive technologies (ARTs) has increased significantly in recent years. While this is partially due to improved access for infertile patients, another contribution to the growth of ART utilization is represented by individuals without infertility, who electively chose to freeze their gametes and embryos for future use, before ever attempting conception spontaneously. Overall, the safety of ART for parents and children is well described and the risks are modest. However, while long-term health consequences for offspring as postulated by the Developmental Origin of Health and Disease (DOHaD) hypothesis are unknown, numerous animal studies suggest a predisposition for chronic diseases like hypertension and glucose intolerance. In this article, we argue that a key difference exists between infertile patients, who need to use ART as the only means to achieve pregnancy, and (likely) fertile patients who elect to use ART techniques as a family planning option. We believe that these two sets of patients are different and their risks–benefit ratios are different. We propose that while all patients should be aware of the risks, patients planning to utilize ART techniques without a diagnosis of infertility should be encouraged to think critically about the additional risks, particularly the “potential” long-term risks that may be imposed from these elective procedures.

Germ Cell Derivation from Pluripotent Stem Cells for Understanding In Vitro Gametogenesis

Cells ◽

10.3390/cells10081889 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1889

Author(s):

Tae-Kyung Hong ◽

Jae-Hoon Song ◽

So-Been Lee ◽

Jeong-Tae Do

Keyword(s):

Stem Cells ◽

Germ Cell ◽

Germ Cells ◽

Pluripotent Stem Cells ◽

Primordial Germ Cells ◽

Obstructive Azoospermia ◽

Female Germ Cell

Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells. Here, we review the recent advances in in vitro male and female germ cell derivation from PSCs and discuss how this technique is used to understand the biological mechanism of gamete development and gain insight into its application in infertility.

The epigenetic effects of assisted reproductive technologies: ethical considerations

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174417000344 ◽

2017 ◽

Vol 8 (4) ◽

pp. 436-442 ◽

Cited By ~ 11

Author(s):

M.-C. Roy ◽

C. Dupras ◽

V. Ravitsky

Keyword(s):

Ethical Issues ◽

Late Onset ◽

Evidence Base ◽

Parents And Children ◽

Children Health ◽

Health And Disease ◽

Ethical Tension ◽

Prospective Parents

The use of assisted reproductive technologies (ART) has increased significantly, allowing many coping with infertility to conceive. However, an emerging body of evidence suggests that ART could carry epigenetic risks for those conceived through the use of these technologies. In accordance with the Developmental Origins of Health and Disease hypothesis, ART could increase the risk of developing late-onset diseases through epigenetic mechanisms, as superovulation, fertilization methods and embryo culture could impair the embryo’s epigenetic reprogramming. Such epigenetic risks raise ethical issues for all stakeholders: prospective parents and children, health professionals and society. This paper focuses on ethical issues raised by the consideration of these risks when using ART. We apply two key ethical principles of North American bioethics (respect for autonomy and non-maleficence) and suggest that an ethical tension may emerge from conflicting duties to promote the reproductive autonomy of prospective parents on one hand, and to minimize risks to prospective children on the other. We argue that this tension is inherent to the entire enterprise of ART and thus cannot be addressed by individual clinicians in individual cases. We also consider the implications of the ‘non-identity problem’ in this context. We call for additional research that would allow a more robust evidence base for policy. We also call upon professional societies to provide clinicians with guidelines and educational resources to facilitate the communication of epigenetic risks associated with ART to patients, taking into consideration the challenges of communicating risk information whose validity is still uncertain.

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

The International Journal of Developmental Biology ◽

10.1387/ijdb.180402gp ◽

2019 ◽

Vol 63 (3-4-5) ◽

pp. 217-222 ◽

Cited By ~ 6

Author(s):

Federica Zacchini ◽

Silvestre Sampino ◽

Adrian M. Stankiewicz ◽

Thomas Haaf ◽

Grazyna E. Ptak

Keyword(s):

Safety Evaluation ◽

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.

The ‘serious’ factor in germline modification

Journal of Medical Ethics ◽

10.1136/medethics-2019-105436 ◽

2019 ◽

Vol 45 (8) ◽

pp. 508-513 ◽

Cited By ~ 5

Author(s):

Erika Kleiderman ◽

Vardit Ravitsky ◽

Bartha Maria Knoppers

Keyword(s):

Human Rights ◽

Genetic Diseases ◽

Well Being ◽

Preimplantation Genetic Testing ◽

Policy Statements ◽

Germline Modification ◽

Health And Disease ◽

Serious Disease

Current advances in assisted reproductive technologies aim to promote the health and well-being of future children. They offer the possibility to select embryos with the greatest potential of being born healthy (eg, preimplantation genetic testing) and may someday correct faulty genes responsible for heritable diseases in the embryo (eg, human germline genome modification (HGGM)). Most laws and policy statements surrounding HGGM refer to the notion of ‘serious’ as a core criterion in determining what genetic diseases should be targeted by these technologies. Yet, this notion remains vague and poorly defined, rendering its application challenging and decision making subjective and arbitrary. By way of background, we begin by briefly presenting two conceptual approaches to ‘health’ and ‘disease’: objectivism (ie, based on biological facts) and constructivism (ie, based on human values). The basic challenge under both is sorting out whether and to what extent social and environmental factors have a role in helping to define what qualifies as a ‘serious’ disease beyond the medical criteria. We then focus on how a human rights framework (eg, right to science and right to the highest attainable health) could integrate the concepts of objectivism and constructivism so as to provide guidance for a more actionable consideration of ‘serious’. Ultimately, it could be argued that a human rights framework, by way of its legally binding nature and its globally accepted norms and values, provides a more universal foundation for discussions of the ethical, legal and social implications of emerging or disruptive technologies.

Re-imagining Reproduction: Unsettling Metaphors in the History of Imperial Science and Commercial Surrogacy in India

Somatechnics ◽

10.3366/soma.2015.0149 ◽

2015 ◽

Vol 5 (1) ◽

pp. 88-103 ◽

Cited By ~ 14

Author(s):

Kalindi Vora

Keyword(s):

The Body ◽

Body Parts ◽

Colonial History ◽

Women's Bodies ◽

Commercial Surrogacy ◽

Art Practices ◽

History Of ◽

Travel Industry

This paper provides an analysis of how cultural notions of the body and kinship conveyed through Western medical technologies and practices in Assisted Reproductive Technologies (ART) bring together India's colonial history and its economic development through outsourcing, globalisation and instrumentalised notions of the reproductive body in transnational commercial surrogacy. Essential to this industry is the concept of the disembodied uterus that has arisen in scientific and medical practice, which allows for the logic of the ‘gestational carrier’ as a functional role in ART practices, and therefore in transnational medical fertility travel to India. Highlighting the instrumentalisation of the uterus as an alienable component of a body and subject – and therefore of women's bodies in surrogacy – helps elucidate some of the material and political stakes that accompany the growth of the fertility travel industry in India, where histories of privilege and difference converge. I conclude that the metaphors we use to structure our understanding of bodies and body parts impact how we imagine appropriate roles for people and their bodies in ways that are still deeply entangled with imperial histories of science, and these histories shape the contemporary disparities found in access to medical and legal protections among participants in transnational surrogacy arrangements.