Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells.
BACKGROUND
Mitochondria are multitasking organelles involved in ATP synthesis, reactive oxygen species (ROS) production, calcium signalling and apoptosis; and mitochondrial defects are known to cause physiological dysfunction, including infertility. The goal of this review was to identify and discuss common themes in mitochondrial function related to mammalian reproduction.


METHODS
The scientific literature was searched for studies reporting on the several aspects of mitochondrial activity in mammalian testis, sperm, oocytes, early embryos and embryonic stem cells.


RESULTS
ATP synthesis and ROS production are the most discussed aspects of mitochondrial function. Metabolic shifts from mitochondria-produced ATP to glycolysis occur at several stages, notably during gametogenesis and early embryo development, either reflecting developmental switches or substrate availability. The exact role of sperm mitochondria is especially controversial. Mitochondria-generated ROS function in signalling but are mostly described when produced under pathological conditions. Mitochondria-based calcium signalling is primarily important in embryo activation and embryonic stem cell differentiation. Besides pathologically triggered apoptosis, mitochondria participate in apoptotic events related to the regulation of spermatogonial cell number, as well as gamete, embryo and embryonic stem cell quality. Interestingly, data from knock-out (KO) mice is not always straightforward in terms of expected phenotypes. Finally, recent data suggests that mitochondrial activity can modulate embryonic stem cell pluripotency as well as differentiation into distinct cellular fates.


CONCLUSIONS
Mitochondria-based events regulate different aspects of reproductive function, but these are not uniform throughout the several systems reviewed. Low mitochondrial activity seems a feature of 'stemness', being described in spermatogonia, early embryo, inner cell mass cells and embryonic stem cells.
Center for Neuroscience and Cell Biology, Department of Zoology, Faculty of Sciences and Technology, University of Coimbra 3004-517, Coimbra, Portugal. jramalho@ci.uc.pt
João
J
Ramalho-Santos
Sandra
S
Varum
Sandra
S
Amaral
Paula C
PC
Mota
Ana Paula
AP
Sousa
Alexandra
A
Amaral
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling; D004622:Embryo, Mammalian / Q000502:physiology; D053595:Embryonic Stem Cells / Q000502:physiology / Q000648:ultrastructure; D004734:Energy Metabolism; D005260:Female; D005854:Germ Cells / Q000502:physiology / Q000648:ultrastructure; D006066:Gonads / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D008954:Models, Biological; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis
D017382:Reactive Oxygen Species; D013256:Steroids; D000255:Adenosine Triphosphate