Contemporary aspects of male gamete (dys)function: aiming towards optimizing the treatment of fertilization disorders

Abstract

At its inception, in vitro fertilization (IVF) was a relatively straightforward procedure encompassing the in vitro insemination of surgically retrieved oocytes and the trans-cervical uterine placement of the ensuing embryos with the goal of overcoming tubal infertility. Since that time, IVF has become the ultimate treatment modality for all infertility indications when standard treatments have failed. While IVF has revolutionized our clinical armamentarium, it has also served as a remarkable scientific tool allowing direct visualization of male and female gamete interaction and assessment of human embryo development, thus enabling reproductive specialists to dissect and better understand the early human reproductive processes. In its earliest stages, IVF was directed at the treatment of female infertility focusing on the role of the oocyte, later to be eclipsed by assisted fertilization techniques that revolutionized the treatment of male factor infertility. The advent of assisted fertilization techniques, from the most simplistic approaches to direct sperm injection, has made it possible for suboptimal male gametes to penetrate the oocyte vestments. The latter technique has shed light on the ultimate function of the spermatozoon and the fascinating process of syngamy. Moreover, the ability to temporally monitor the cleaving embryo in vitro has enabled us to ascertain the individual steps involved in the development of the conceptus from syngamy to blastocyst as well as to shed light on hitherto unapproachable infertility etiologies. After over 30 years of IVF and 20 years of intracytoplasmic sperm injection (ICSI), it seems appropriate to focus on our present understanding and the state of scientific knowledge of the male gamete. The present issue of Views and Reviews will describe the history and development of ICSI — the ultimate technique to treat male infertility — and review the current indications for assisted fertilization in terms of therapeutic outcome, safety, and future perspectives (1Palermo G.D. Neri Q.V. Monahan D. Kocent J. Rosenwaks Z. Development and current applications of assisted fertilization.Fertil Steril. 2012; 97: 248-259Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar). Other contributions will describe the currently available assays to screen for male factor infertility and sperm function. Although the semen analysis has been utilized for several decades as the cornerstone for assessing male fertility (dys)function, interpretation and clinical correlations still remain a challenge (2De Jonge C. Semen Analysis: Looking for an upgrade in class.Fertil Steril. 2012; 97: 260-266Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar). The recent understanding of the sperm epigenetic status in regards to protamination, specific localization/modifications of retained histones, and DNA methylation may delineate the role of the male gamete on embryogenesis and eventually in the establishment of totipotency of the embryo. This may help to unravel hitherto undiagnosable causes of impaired fertility and possibly provide insights into transmission of genetic risks (3Carrell D.T. Epigenetics of the male gamete.Fertil Steril. 2012; 97: 267-274Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar). In fact, it has been documented that the nucleus of mature spermatozoa contains a complex population of RNAs that are transcriptionally inert. These small molecules which appear to orchestrate extraordinary spermiogenic modifications, may also aid in discriminating and assessing spermatozoal function that may serve as investigational and diagnostic tools for male infertility (4Hamatani T. Human spermatozoal RNAs.Fertil Steril. 2012; 97: 275-281Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar). It has become evident that the role of the spermatozoon as a simple mobile device to deliver the male genome should be reconsidered and reinterpreted as a cell characterized by its unusual shape, extraordinary motility, resilience to environmental aggressors, and capable of its own reshaping during spermatogenesis. Upon reaching the oocyte, the spermatozoon triggers egg activation, orchestrates in a preprogrammed pattern peri- and post-fertilization events in the oocyte, thus, inevitably controlling early embryo development. Ideally, the utilization of novel diagnostic techniques will not only improve our abilities to assess sperm (dys)function, they will also allow us to discriminate the spermatozoon’s contribution to early embryo development.