The remarkable complexity of the molecular events governing adhesion and fusion of the male and female gametes is becoming apparent. Novel research suggests that these highly specific cellular interactions are facilitated by multiprotein complexes that are delivered to and/or assembled on the surface of the gametes by molecular chaperones in preparation for sperm–egg interaction. While the activation of these molecular chaperones and the mechanisms by which they shuttle proteins to the surface of the cell remain the subject of ongoing investigation, a compelling suggestion is that these processes are augmented by dynamic membrane microdomains or lipid rafts that migrate to the apical region of the sperm head after capacitation. Preliminary studies of the oocyte plasma membrane have also revealed the presence of lipid rafts comprising several molecular chaperones, raising the possibility that similar mechanisms may be involved in the activation of maternal fusion machinery and the regulation of oocyte plasma membrane integrity. Despite these findings, the analysis of oocyte surface multiprotein complexes is currently lacking. Further analyses of the intermediary proteins that facilitate the expression of key players in sperm–egg fusion are likely to deliver important insights into this unique event, which culminates in the cytoplasmic continuity of the male and female gametes.
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Elizabeth G Bromfield and Brett Nixon
Elizabeth G Bromfield, R John Aitken, Zamira Gibb, Sarah R Lambourne, and Brett Nixon
While IVF has been widely successful in many domesticated species, the development of a robust IVF system for the horse remains an elusive and highly valued goal. A major impediment to the development of equine IVF is the fact that optimised conditions for the capacitation of equine spermatozoa are yet to be developed. Conversely, it is known that stallion spermatozoa are particularly susceptible to damage arising as a consequence of capacitation-like changes induced prematurely in response to semen handling and transport conditions. To address these limitations, this study sought to develop an effective system to both suppress and promote the in vitro capacitation of stallion spermatozoa. Our data indicated that the latter could be achieved in a bicarbonate-rich medium supplemented with a phosphodiesterase inhibitor, a cyclic AMP analogue, and methyl-β-cyclodextrin, an efficient cholesterol-withdrawing agent. The populations of spermatozoa generated under these conditions displayed a number of hallmarks of capacitation, including elevated levels of tyrosine phosphorylation, a reorganisation of the plasma membrane leading to lipid raft coalescence in the peri-acrosomal region of the sperm head, and a dramatic increase in their ability to interact with heterologous bovine zona pellucida (ZP) and undergo agonist-induced acrosomal exocytosis. Furthermore, this functional transformation was effectively suppressed in media devoid of bicarbonate. Collectively, these results highlight the importance of efficient cholesterol removal in priming stallion spermatozoa for ZP binding in vitro.
R John Aitken, Elizabeth G Bromfield, and Zamira Gibb
In brief
Many aspects of the reproductive process are impacted by oxidative stress. This article summarizes the chemical nature of reactive oxygen species and their role in both the physiological regulation of reproductive processes and the pathophysiology of infertility.
Abstract
This article lays out the fundamental principles of oxidative stress. It describes the nature of reactive oxygen species (ROS), the way in which these potentially toxic metabolites interact with cells and how they impact both cellular function and genetic integrity. The mechanisms by which ROS generation is enhanced to the point that the cells’ antioxidant defence mechanisms are overwhelmed are also reviewed taking examples from both the male and female reproductive system, with a focus on gametogenesis and fertilization. The important role of external factors in exacerbating oxidative stress and impairing reproductive competence is also examined in terms of their ability to disrupt the physiological redox regulation of reproductive processes. Developing diagnostic and therapeutic strategies to cope with oxidative stress within the reproductive system will depend on the development of a deeper understanding of the nature, source, magnitude, and location of such stress in order to fashion personalized treatments that meet a given patient’s clinical needs.
Jacinta H Martin, Brett Nixon, Shenae L Cafe, R John Aitken, Elizabeth G Bromfield, and Tessa Lord
In brief
Post-ovulatory ageing of oocytes leads to poor oocyte and embryo quality as well as abnormalities in offspring. This review provides an update on the contributions of oxidative stress to this process and discusses the current literature surrounding the use of antioxidant media to delay post-ovulatory oocyte ageing.
Abstract
Following ovulation, the metaphase II stage oocyte has a limited functional lifespan before succumbing to a process known as post-ovulatory oocyte ageing. This progressive demise occurs both in vivo and in vitro and is accompanied by a deterioration in oocyte quality, leading to a well-defined sequelae of reduced fertilisation rates, poor embryo quality, post-implantation errors, and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been characterised, less is known regarding the molecular mechanisms that drive this process. This review presents an update on the established relationships between the biochemical changes exhibited by the ageing oocyte and the myriad of symptoms associated with the ageing phenotype. In doing so, we consider the molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We highlight the mounting evidence that oxidative stress acts as an initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to disrupt mitochondrial function and directly damage multiple intracellular components of the oocyte such as lipids, proteins, and DNA. Finally, this review addresses emerging strategies for delaying post-ovulatory oocyte ageing with emphasis placed on the promise afforded by the use of selected antioxidants to guide the development of media tailored for the preservation of oocyte integrity during in vitro fertilisation procedures.