Mitochondria transfer can enhance the murine embryo development

Abstract

Our results for the murine model provide direct scientific evidence that mitochondrial transfer improves embryonic development. However, potential risks such as mitochondrial heteroplasmy, nuclear-mitochondrial interaction and epigenetic aspects all deserve further evaluation before mitochondrial transfer is applied clinically.

Mitochondrial functions on oocytes and preimplantation embryos

“…Mitochondria form aggregates with the smooth endoplasmic reticulum (SER), Cummins et al, 1997;Cox and Spradling, 2003;Mitochondrial distribution Wilding et al, 2001Torner et al, 2004;Nishi et al, 2003Mitochondrial movement van Blerkom, 1991Cox and Spradling, 2003;mtDNA content Reynier et al, 2001Spikings et al, 2007mtDNA mutation Yesodi et al, 2002Hsieh et al, 2004Mitochondrial polarity van Blerkom et al, 2003 2007 Function in calcium regulation Machaty et al, 1997;Krisher, 2004;Whitaker, 2008 Mitochondrial dysfunction Tarín, 1996;Eichenlaub-Ritter, 1998;Yin et al, 1998;Ottolenghi et al, 2004;Thouas et al, 2004;Zhang et al, 2006Mitochondria transfer Pinkert et al, 1997Malter and Cohen, 2002;Kong et al, 2004;Yi et al, 2007 a Studies involved in oocytes and embryos and these aggregates are apparently involved in the energy production and deposition before fertilization (Torner et al, 2004). Mammalian oocyte maturation relies not only on a high level of ATP for nuclear envelope breakdown, but also on intracellular calcium, which is derived from the endoplasmic reticulum (ER) and mitochondria (Krisher, 2004).…”

“…Pinkert et al(1997) primarily microinjected mitochondria isolated from Mus spretus liver samples into fertilized ovary, and made mitochondrial genome applied for experimental and therapeutic purposes. Yi et al(2007) have provided direct scientific evidence on the improvement of embryo development after mitochondrial transfer. Microinjecting a certain level of mitochondria into oocytes may compensate for the insufficiency of active mitochondria and raise the morula formation rate.…”

Human granulosa luteal cell oxidative phosphorylation function is not affected by age or ovarian response

“…Ooplasmic transfer of mitochondria, from young mouse oocytes into mature older oocytes, has resulted in an increased fertilization rate and enhanced embryonic development (7). A drawback of mitochondrial transfer from a different donor is the mitochondrial hetroplasmy resulting in an abnormal mouse phenotype (8).…”

The next (re)generation of ovarian biology and fertility in women: is current science tomorrow's practice?

“…Such delivery of autologous OSC-derived mitochondria into human oocytes during intracytoplasmic sperm injection (ICSI) may provide the energy boost needed to overcome existing mitochondrial deficits due to aging or other factors that negatively affect either fertilization outcome or post-fertilization embryonic competency. Considering the clinical success already reported from transfer of heterologous female germ cell mitochondria into eggs of women with a history of IVF failure (65–68), along with related studies using animal models showing improved embryonic developmental potential of fertilized eggs after mitochondrial transfer (69, 70), AUGMENT may hold considerable promise for clinical development and testing in the near-term.…”