The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment.

Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. With all of these fertility check points, it shows more promise than conventional semen parameters from a diagnostic perspective. Despite this, few infertility clinics use it routinely. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths and weaknesses and clinical applicability of current sperm DNA fragmentation tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of increased oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. As those working in this field of clinical research, we conclude that DNA damage in human spermatozoa is an important attribute of semen quality which should be carefully assessed in the clinical work up of infertile couples and that properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.

The role of molecular chaperones in mouse sperm-egg interactions.

Fertilization is a unique and exquisitely choreographed cellular interaction between the male and female gamete that results in the creation of a genetically unique individual. Despite the fundamental importance of fertilization, there remains a dearth of information about the basic biochemical mechanisms that underpin this process. One of the key issues that remain unresolved is the molecular basis of sperm-egg recognition. From the female perspective, it is well established that the sperm recognition sites reside in the zona pellucida (ZP), an acellular coat that surrounds the oocyte. In contrast, numerous studies into the cognate zona receptors residing on the sperm surface have failed to shed significant light on the biochemical identity of these molecules. Such difficulties may, in part, have arisen because investigations have traditionally been based on the precept that the zona receptor represents a single molecular entity that is constitutively expressed on the sperm surface. While such a view holds obvious appeal, it fails to account for growing evidence that gamete interaction is not mediated by a simple lock-and-key mechanism. In this review, we present a novel hypothesis in which the zona recognition site is portrayed as a multimeric molecular structure that is assembled into a functional complex during a maturation process known as 'capacitation'. Furthermore, we consider the possibility that this previously cryptic complex is assembled and delivered to the outer surface of the sperm plasma membrane through the concerted action of several members of the molecular chaperone family of proteins.