CYIL vol. 9 (2018)

MARTIN ŠOLC CYIL 9 ȍ2018Ȏ In case of mtDNA, however, the situation is rather unique: mitochondria can be considered part of the germline only in oocytes, and not in sperm. In other words, MRT in female embryos arguably represents a germline modification which is transmissible to the next generation, while the same procedure in male embryos does not. An example of its ethical (and legal) relevance can be found in the United States National Academies of Sciences, Engineering, and Medicine special committee report from 2016 that recommends carrying out the initial clinical investigations of MRT only in male embryos. According to the committee, the Food and Drug Administration “could consider extending MRT research to include the transfer of female embryos” not before “clear evidence of safety and efficacy from male cohorts (…) were available” . 22 There have been detected small amounts of paternally inherited mtDNA molecules in mice after several generations of interspecific backcrosses (i.e. breeding between genetically similar individuals). 23 However, this finding alongside the following experiments in mice did not truly shatter the notion of an exclusive maternal mtDNA transmission. On the other hand, it led scientists to gain a more detailed knowledge of the mechanisms that stand behind the disappearance of paternal mtDNA in the early stages of embryogenesis. 24 There has only been one documented case of paternal mtDNA transmission in humans. A young man suffered from a lifelong severe exercise intolerance, not being able to participate in sports or run for more than a few steps. DNA tests revealed that there were two types of mtDNA in his body, presumably each of them coming from a different parent. The mtDNA from the father was only found in the skeletal muscle tissue. The patient was diagnosed with isolated mitochondrial myopathy. 25 Unlike his healthy father’s, the son’s paternally inherited mtDNA contained a mutation 26 responsible for the disease. 27 22 The National Academies of Sciences, Engineering, and Medicine Committee on the ethical and social policy considerations of novel techniques for prevention of maternal transmission of mitochondrial DNA diseases. Mitochondrial replacement techniques: Ethical and social policy considerations. The National Academic Press, Washington, D.C. 2016, p. xv. < https://www.nap.edu/read/21871/chapter/1> accessed 22 May 2018. 23 GYLLENSTEN, Ulf, WHARTON, Dan, JOSEFSSON, Agneta, WILSON, Allan C. Paternal inheritance in mitochondrial DNA in mice. Nature. (1991, Vol. 352, No. 6332), pp. 255-257. 24 These mechanisms include selective destruction or inactivation of paternal mtDNA by nuclear-encoded proteins, or simply the dilution of paternal mtDNA by the oocyte (maternal) mtDNA. SCHWARTZ, Marianne, VISSING, John. Paternal Inheritance of Mitochondrial DNA. The New England Journal of Medicine. (2002, Vol. 347, No. 8), p. 576. accessed 18 May 2018. See also, for example, SHITARA, Hiroshi, KANEDA, Hideki, SATO, Akitsugu, INOUE, Kimiko, OGURA, Atsuo, YONEKAWA, Hiromichi, HAYASHI, Jun-Ichi. Selective and continuous elimination of mitochondria microinjected into mouse eggs from spermatids, but not from liver cells, occurs throughout embryogenesis. Genetics. (2000, Vol. 156, No. 3), pp. 1277-1284. 25 Mitochondrial myopathies are neuromuscular diseases caused by damage to the patient’s mitochondria. See National Institute of Neurological Disorders and Stroke. Mitochondrial Myopathies Information Page. (4 May 2018.) accessed 19 May 2018. 26 Specifically, the myopathy was caused by a deletion in one of the genes of the patient’s mtDNA. Deletion is a loss of a certain sequence of nucleotides (the basic units of DNA). In the said case, there occurred a 2-bp mtDNA deletion in the ND2 gene. SCHWARTZ, Marianne, VISSING, John. Paternal Inheritance of Mitochondrial DNA. The New England Journal of Medicine. (2002, Vol. 347, No. 8), pp. 576-580. accessed 18 May 2018. 27 This was explained either by a spontaneous mutation in early embryogenesis or in the paternal germline. It is also possible that the mutation was present in the father’s mtDNA at a low level in other tissues. Ibid.

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