❓ Why are mitochondria in oocytes different from other cells? Also, why do they appear differently?

❕ The unique features of mitochondria (mtDNA copy number, morphology and functionality) in the oocyte have been determined by evolution. Specifically, the number of mitochondria within cells is often an indication of the activity of that cell. The capability to generate ATP in an oocyte is critical for successful maturation of the cytoplasm and nucleus in preparation for fertilization and completion of meiosis II.¹ In addition, as the female germ cell the oocyte provides all the mitochondria required for embryo development because mitochondria from sperm are degenerated immediately after fertilization. Good quality oocytes containing optimal mitochondrial numbers and sufficient levels of ATP (at least 2 pM)² produce higher quality blastocysts after fertilization.³

The mitochondria in the oocyte are structurally distinct – they are spherical with few truncated cristae surrounding a matrix of high electron density.⁴ The mitochondria in the oocyte are the primary source of ATP required for early embryo development^2,5 since early embryos do not express the replication factors required to increase copy numbers of mitochondria until around the time of implantation.

These mitochondria are then able to undergo stage-specific structural transformations during the preimplantation phase, including elongation and development of an extensive array of cristae that completely traverse a matrix of progressively lower electron density.^6-10 Replication of the mtDNA then occurs around the time of blastocyst formation – first in the trophectoderm and then within the overall embryo.^1,11

Taken together, the unique features of oocyte make its mitochondria very different from other somatic cells. The morphology, number and activity of mitochondria in oocytes are indispensable for fertilization and early embryo development.

References

1. St John JC, Facucho‐Oliveira J, Jiang Y, Kelly R, and Salah R. "Mitochondrial DNA transmission, replication and inheritance: a journey from the gamete through the embryo and into offspring andembryonic stem cells," Human Reproduction Update 2010; 16(5): 488–509.
2. Van Blerkom J, Davis PW, and Lee J. "ATP content of human oocytes and developmental potential andoutcome after in‐vitro fertilization and embryo transfer," Human Reproduction 1995, 10(2): 415–424.
3. Takeuchi T, Q. V. Neri, Y. Katagiri, Z. Rosenwaks, and G. D. Palermo, "Effect of treating inducedmitochondrial damage on embryonic development and epigenesis," Biology of Reproduction 2005,72(3): 584–592.
4. Motta, P, Nottola, S, Makabe, S, Heyn, R. Mitochondrial morphology in human fetal and adult femalegerm cells. Hum. Reprod. 2000, 15(suppl 2), 129–147.
5. Dumollard, R, Duchen, M, Carroll, J. The role of mitochondrial function in the oocyte and embryo.Curr. Top. Dev. Biol. 2007, 77: 21–49.
6. Van Blerkom, J., Manes, C., Daniel, J.C., 1973. Development of preimplantation rabbit embryos in vivoand in vitro. I. An ultrastructural comparison. Dev. Biol. 35, 262–282.
7. Van Blerkom J., Motta P. The cellular basis of mammalian reproduction, Urban & Schwarzenberg,Baltimore – Munich 1979, 2 (3): 185.
8. Van Blerkom, J., 1989. Developmental failure in human reproduction associated with preovulatoryoogenesis and preimplantation embryogenesis. In: Van Blerkom, J., Motta, P. (Eds.), Ultrastructure of Human Gametogenesis and Embryogenesis. Kluwer Acad. Pub, pp. 125–180.
9. Van Blerkom, J., 1993. Development of human embryos to the hatched blastocyst stage in the presence or absence of a monolayer of Vero cells. Hum. Reprod. 8, 1525–1539.
10. Sathananthan, H., Trounson, A., 2000. Mitochondrial morphology during human preimplantation embryogenesis. Hum. Reprod. 15 (Suppl. 2), 148–159.
11. Thouas GA, Trounson AO, and Jones GM. “Effect of female age on mouse oocyte developmental competence following mitochondrial injury,” Biology of Reproduction, vol. 73, no. 2, pp. 366–373, 2005.

❓ Do mitochondria change when they are diluted in somatic cells during life?

❕ Once the embryo begins to replicate its own mitochondria and those mitochondria begin to divide into specific cell types during gastrulation, those mitochondria develop in a manner consistent with the function of that cell.

Over the course of a lifetime, mitochondria in all cells, including somatic cells, undergo mutations and deletions. Mitochondrial DNA resides close to the electron transport chain which produces reactive oxygen species (ROS) as a byproduct of ATP production. This causes damage to mitochondrial DNA (mtDNA) which accumulates with age. While there are many known/reported mtDNA mutations the most common mtDNA deletion in human cells results from a 4977-base pair deletion. The ‘common deletion’ has not been observed in mitochondria from EggPCSM cells.¹

References

1. Woods DC, Tilly JL. Autologous germline mitochondrial energy transfer (AUGMENT℠) in human assisted reproduction. Semin Reprod Med 2015; 33(06): 410‐421.

❓ What is the patient profile for the AUGMENTSM treatment?

❕ The AUGMENT treatment is recommended for patients diagnosed with poor egg health or undiagnosed infertility and who want to have their own biological child.

❓ Is there a means of checking mitochondrial activity prior to transfer?

❕ There are currently no assays available that assess mitochondrial activity and still allow for the mitochondria to be transferred.

❓ Where is the AUGMENT treatment available?

❕ The AUGMENT treatment is available in select countries globally and is not available in the United States. More information about the availability of AUGMENT is available at www.augmenttreatment.com.