Regulatory roles for mitochondria in the peri-implantation mouse blastocyst: possible origins and developmental significance of differential ΔΨm

Abstract

Studies of mitochondria in mouse and human oocytes and preimplantation stage embryos have focused primarily on their metabolic capacity to generate ATP. However, it is becoming increasingly apparent that mitochondria are also regulatory agents in other processes involved in the establishment of developmental competence, including calcium homeostasis and apoptosis. The magnitude of the inner mitochondrial membrane potential, or its polarity (DCm), is a physiochemical property of mitochondria related to levels of organelle activity, and differences in the magnitude and spatial distribution of high-and low-polarized mitochondria have been suggested to influence oocyte and early embryo competence. Here, we investigated mitochondrial polarity in normal and diapausing peri-implantation-stage mouse blastocysts, and their corresponding outgrowths, for indications of cell-type-specific regulatory functions or activities in which these organelles may be engaged. The results demonstrate that cell-type-and location-specific domains of differential DCm exist in the peri-implantation blastocyst and remain unchanged during blastocyst outgrowth and during delayed implantation, which for the latter, is accompanied by the suppression of mitochondrial oxidative phosphorylation. Our findings demonstrate that cell-type-specific DCm in the peri-implantation blastocyst is not an intrinsic property of the corresponding mitochondria but one that can be mediated by the dynamics of intercellular contact. Cells with high-or low-polarized mitochondria are differentially affected by photosensitization, with developmental consequences related to embryo behavior and outgrowth performance. Differences in polarity are discussed with respect to the participation of mitochondria in regulatory and morphogenetic processes in the normal periimplantation embryo. The persistence of high DCm in the diapausing embryo is suggested to be associated with the regulation of levels of cytoplasmic free calcium and the ability of the embryo to reactivate development when delayed implantation terminates. Reproduction (2006) 131 961-976

Serotonin in pre-implantation mouse embryos is localized to the mitochondria and can modulate mitochondrial potential

“…In human embryos, mitochondrial potential has been reported to be negatively correlated with maternal age and embryos having lower mitochondrial potential have slower developmental rates (Wilding et al 2001). Other reports have suggested that arrested two-cell and diapausing embryos display high mitochondrial potential (Acton et al 2004, Van Blerkom et al 2006. All of these suggest that mitochondrial potential plays an important role in early embryonic development and serotonin can affect development by modulating it.…”

“…We also report for the first time that the high levels of serotonin are localized to mitochondria in mammalian embryos, where it modulates mitochondrial potential. This is of significance because mitochondrial potential is known to affect development (Wilding et al 2001, Acton et al 2004, Van Blerkom et al 2006. The presence of serotonin in mitochondria playing a role in the regulation of mitochondrial potential in early developmental stages along with the establishment of a technique that allows one to observe the distribution and levels of serotonin in living embryos affords exciting opportunities for further studies.…”

Ceramide and mitochondrial function in aging oocytes: joggling a new hypothesis and old players

“…This has been demonstrated in human oocytes by Van Blerkom et al (1995). Recently, several studies on the metabolic activity of oocytes and early embryos concluded that, although their mitochondria have low activity, they are constitutively active; and that maintenance of that low-level activity is necessary and sufficient for ongoing development (Cummins 2004a,b, Van Blerkom 2004, 2011, Van Blerkom et al 2006, Dumollard et al 2007). …”

“…Mitochondria are the most prominent cell organelles in oocytes, and they represent one of the most important maternal contributions to early embryogenesis (Van Blerkom 2004, 2011, Van Blerkom et al 2006, Dumollard et al 2007, Eichenlaub-Ritter et al 2011. Owing to their role in the production of cellular energy as well as in the control of cell death, these organelles are at the center of death and life decisions in most cells, including the oocyte (Perez et al 2000, Wang 2001, Danial & Korsmeyer 2004.…”

Efecto De La Aplicación De Gonadotropinas Recombinantes Humanas Sobre La Producción Y Calidad De Ovocitos Y Embriones en Coneja

“…En este contexto, dado que la ubicación de las mitocondrias varía a lo largo de la maduración ovocitaria, acumulándose en aquellas zonas en las que la demanda de energía se incrementa ( Wang et al, 2009;Van Blerkom, 2010) y se ha relacionado con la capacidad de desarrollo de los ovocitos (Nagai et al, 2006), su evidenciación a través de la tinción con rodamina 123 (Van Blerkom, 1991;Sohn et al, 2002;Van Blerkom et al, 2006) o de otras tinciones fluorescentes (Nagai et al, 2006), sería una herramienta útil para su valoración.…”