Although mitochondria are best known for being the eukaryotic cell powerhouses, these organelles participate in various cellular functions besides ATP production, such as calcium homoeostasis, generation of reactive oxygen species (ROS), the intrinsic apoptotic pathway and steroid hormone biosynthesis. The aim of this review was to discuss the putative roles of mitochondria in mammalian sperm function and how they may relate to sperm quality and fertilisation ability, particularly in humans. Although paternal mitochondria are degraded inside the zygote, sperm mitochondrial functionality seems to be critical for fertilisation. Indeed, changes in mitochondrial integrity/functionality, namely defects in mitochondrial ultrastructure or in the mitochondrial genome, transcriptome or proteome, as well as low mitochondrial membrane potential or altered oxygen consumption, have been correlated with loss of sperm function (particularly with decreased motility). Results from genetically engineered mouse models also confirmed this trend. On the other hand, increasing evidence suggests that mitochondria derived ATP is not crucial for sperm motility and that glycolysis may be the main ATP supplier for this particular aspect of sperm function. However, there are contradictory data in the literature regarding sperm bioenergetics. The relevance of sperm mitochondria may thus be associated with their role in other physiological features, particularly with the production of ROS, which in controlled levels are needed for proper sperm function. Sperm mitochondria may also serve as intracellular Ca2 + stores, although their role in signalling is still unclear.
Alexandra Amaral, Bárbara Lourenço, Mónica Marques and João Ramalho-Santos
Bibiana Correia, Maria Inês Sousa and Joao Ramalho-Santos
Reproduction depends on many factors, from gamete quality to placenta formation, to fetal development. The mTOR pathway is emerging as a major player that integrates several cellular processes in response to a variety of environmental cues that are relevant in many aspects of reproduction. This review provides a general overview, summarizing the involvement of the two mTOR complexes (mTORC1 and mTORC2) in integrating signaling pathways, sensing environmental status, and managing physiological processes inherent to successful reproductive outcomes and pluripotent stem cell function. As a well-known governor of multiple cellular functions, it is not surprising that mTOR has a key regulatory role in determining cell quiescence or differentiation. In the gonads mTOR helps maintain spermatogonial stem cell and follicle identity and tightly regulates differentiation in both systems to ensure proper gamete production. The mTOR pathway is also known to prevent premature follicle exhaustion, while also controlling the blood-testis barrier in the male gonad. In stem cells mTOR again seems to have a role in controlling both pluripotency and differentiation, mirrored by its in vivo roles in the embryo, notably in regulating diapause. Finally, although there are clearly more complex systems intertwined in placental function, mTOR seems to serve as an early checkpoint for development progression and successful implantation.
Mónica Marques, Ana Paula Sousa, Artur Paiva, Teresa Almeida-Santos and João Ramalho-Santos
We have applied the mitochondria-specific superoxide fluorescent probe MitoSOX Red (MitoSOX) to detect mitochondria-specific reactive oxygen species (mROS) production in human sperm samples using flow cytometry. We show that human ejaculates are heterogeneous in terms of mROS production, with three subpopulations clearly detectable, comprising sperm that produce increasing amounts of mROS (MitoSOX−, MitoSOX+, and MitoSOX++). The sperm subpopulation producing the lowest amount of mROS represented the most functional subset of male gametes within the ejaculate, as it was correlated with the highest amount of live and non-apoptotic sperm and increased both in samples with better semen parameters and in samples processed by both density-gradient centrifugation and swim-up, both known to select for higher quality sperm. Importantly, the MitoSOX− subpopulation was clearly more prevalent in samples that gave rise to pregnancies following assisted reproduction. Our work, therefore, not only describe discreet human sperm heterogeneity at the mROS level but also suggests that mROS may represent a strategy to both evaluate sperm samples and isolate the most functional gametes for assisted reproduction.
Free Portuguese abstract
A Portuguese translation of this abstract is freely available at http://www.reproduction-online.org/content/147/6/817/suppl/DC1