Three-parent babies: Mitochondrial replacement therapies

Abstract

The mitochondria are intracellular organelles, and just like the cell nucleus they have their own genome. They are extremely important for normal body functioning and are responsible for ATP production -the main energy source for the cell. Mitochondrial diseases are associated with mutations in mitochondrial DNA and are inherited exclusively from the mother. They can affect organs that depend on energy metabolism, such as skeletal muscles, the cardiac system, the central nervous system, the endocrine system, the retina and liver, causing various incurable diseases. Mitochondrial replacement techniques provide women with mitochondrial defects a chance to have normal biological children. The goal of such treatment is to reconstruct functional oocytes and zygotes, in order to avoid the inheritance of mutated genes; for this the nuclear genome is withdrawn from an oocyte or zygotes, which carries mitochondrial mutations, and is implanted in a normal anucleated cell donor. Currently, the options of a couple to prevent the transmission of mitochondrial diseases are limited, and mitochondrial donation techniques provide women with mitochondrial defects a chance to have normal children. The nuclear genome can be transferred from oocytes or zygotes using techniques such as pronuclear transfer, spindle transfer, polar body transfer and germinal vesicle transfer. This study presents a review of developed mitochondrial substitution techniques, and its ability to prevent hereditary diseases.

Mitochondrial enrichment in infertile patients: a review of different mitochondrial replacement therapies

“…PBT consists in the relocation of the PB1 or PB2, instead of the nuclear genetic material from the oocyte, to a healthy cytoplasm. 64 • PB1T: PB1 is isolated from the compromised MII oocyte and is relocated in the enucleated donor oocyte. This oocyte is subsequently fertilised with the partner sperm, which gives rise to a reconstituted zygote with healthy mtDNA, as well as the genetic material from the patient PB1 and sperm in the form of pronuclei.…”

“…PBT consists in the relocation of the PB1 or PB2, instead of the nuclear genetic material from the oocyte, to a healthy cytoplasm. 64 …”

Técnicas de substituição de DNA mitocondrial para reduzir a transmissão da Síndrome de Leigh

“…Algumas clínicas oferecem diagnóstico genético pré-implantacional (PGD) para medir o nível de heteroplasmia de mtDNA em embriões desenvolvidos in vitro. Essa conduta não é um padrão, pois devido ao padrão de multiplicação de mitocôndrias durante o desenvolvimento embrionário, o PGD não apresenta resultados confiáveis quanto à prevenção transmissão de mutação, uma vez que a taxa de mtDNA para um embrião se desenvolver sem manifestar a doença não é conhecido 10 .…”

“…A notícia foi veiculada mundialmente pela mídia como o nascimento do bebê de três pais (Three-parent baby). Apesar de a técnica ter sido rapidamente aplicada na rotina clínica, podem ocorrer incompatibilidades entre os genomas mitocondrial e nuclear resultantes do processo e a técnica é recente e não bem discutido ainda 10 . Assim, este trabalho objetiva revisar os sinais e sintomas clássicos e as principais alterações moleculares da SL, bem como revisa as técnicas de transferência de DNA nuclear utilizadas em reprodução assistida que objetivam reduzir a chance de transmissão da SL e de outras síndromes causadas por mutações no mtDNA para os filhos de mães com a síndrome.…”

Lycopene Improves In Vitro Development of Porcine Embryos by Reducing Oxidative Stress and Apoptosis

“…Mitochondria are important intracellular organelles responsible for energy production [ 9 ]. Previous studies have demonstrated that mitochondria perform an important role in cell death pathways [ 10 , 11 ].…”