Differential mitochondrial distribution in human pronuclear embryos leads to disproportionate inheritance between blastomeres: relationship to microtubular organization, ATP content and competence.
It has been suggested that mitochondrial DNA defects that effect metabolic capacity may be a proximal cause of failures in oocyte maturation, fertilization, or early embryonic development. Here, the distribution of mitochondria was examined by scanning laser confocal microscopy in living human pronuclear oocytes and cleavage stage embryos, followed either by measurements of the net ATP content of individual blastomeres or anti-tubulin immunofluorescence to determine the relationship between mitochondrial distribution and microtubular organization. The results indicate that specific patterns of perinuclear mitochondrial aggregation and microtubular organization are related, and that asymmetrical mitochondrial distributions at the pronuclear stage can result in some proportion of blastomeres with reduced mitochondrial inheritance and diminished ATP generating capacity. While the inability to divide appears to be a development consequence for an affected blastomere, for the embryo, reduced competence may occur during cleavage if several blastomeres inherit a mitochondrial complement inadequate to support normal cellular functions. The findings provide a possible epigenetic explanation for the variable developmental ability expressed within cohorts of morphologically normal early cleavage stage human embryos obtained by in-vitro fertilization.
Van Blerkom
J
J
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80302 and Colorado Reproductive Endocrinology, Rose Medical Center, Denver, CO 80220, USA. vanblerk@spot.colorado.edu
Davis
P
P
Alexander
S
S
D000255:Adenosine Triphosphate / Q000032:analysis* / Q000378:metabolism; D000328:Adult; D001757:Blastomeres / Q000502:physiology / Q000648:ultrastructure*; D002970:Cleavage Stage, Ovum / Q000648:ultrastructure*; D004622:Embryo, Mammalian / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D018613:Microscopy, Confocal; D008870:Microtubules / Q000648:ultrastructure*; D008928:Mitochondria / Q000648:ultrastructure*; D009865:Oocytes / Q000648:ultrastructure*; D020112:Rhodamine 123
D005456:Fluorescent Dyes; D020112:Rhodamine 123; D000255:Adenosine Triphosphate