Andrology is the discipline that corresponds to gynecology for men, but while the latter is a well-established discipline, the former is still an emerging field. A simple definition of andrology will include the study of all subjects that may affect the male reproductive system. In the last years, a striking large number of topics has emerged in this field and there is an increasing amount of information that may be useful for graduate, post-graduate and even well-established researchers. Herein, we summarize the available information so far in this area, presenting a review and a critical analysis of the available data on the most relevant subjects with interest to andrology, with emphasis on the biochemistry of the processes. This e-book is divided into 14 chapters, all coordinated by Dr. Marco G. Alves and Prof. Pedro F. Oliveira.

Andrology Current and Future Developments (Volume 1) (Biochemistry of Andrology)


The first chapter is a brief introduction to the historical evolution of andrology and how biochemistry has emerged as a partner, contributing to the emerging relevance of this discipline. The second chapter describes general considerations on testis physiology, testicular anatomy and functional organization, as well as its embryonic development. The third chapter discusses the basic aspects of testicular cells physiology and function. The fourth chapter presents the basic aspects of spermatogenesis, a key event for species propagation, from a biochemical perspective. It is mainly focused on the mechanisms responsible for postnatal testis development but it also presents an overview on the complex events that control the spermatogenic cycle. Many of those changes are under the action and function of male-associated hormones that trigger signaling pathways thus, the fifth chapter is dedicated to those issues. The endocrine regulation of sexual maturation and sperm formation is still a matter of great debate and with an enormous interest. In the sixth chapter, the transition period between childhood and adulthood is discussed, particularly the biochemical changes that control pivotal events responsible for the sexual maturation of the individuals. There is also an overview on puberty-associated disorders, pinpointing the clinical features that should be taken into consideration and the deleterious signals that may occur until sexual maturation is achieved. In the seventh chapter, the biochemical events occurring in the epididymis that end-up in sperm maturation, are discussed. It also discussed the structural organization of epididymal epithelial cells and secretory proteins and their involvement on the spermatozoa modifications that occur during the process of maturation. The eighth chapter is dedicated to the formation and biochemical properties of seminal plasma and male accessory glands. Those changes are essential for spermatozoa to acquire fertility capacity. In the ninth chapter, the functional and physiological aspects of spermatozoa, as well as its epigenome are presented, which may have an enormous implication to the success of the pregnancy and latter to the offspring health. The male gamete is very dynamic and has to move, capacitate, migrate through the female tract, bind to the egg membrane and fuse to the oocyte, resulting in a viable embryo. The tenth chapter is dedicated to the sequential modifications and the molecular mechanisms that occur during the journey of spermatozoa through the female reproductive tract since they have a pivotal role in couple’s fertility success and offspring health. Those events may be compromised by several factors that compromise male reproductive health. Congenital disorders, such as hypospadias, undescended testis, testicular atrophy and testicular cancer have increased among young males and even erectile dysfunction and sexually transmitted diseases are still problems that compromise male reproductive health. These issues are discussed in chapter eleven. The twelfth chapter discusses how the pandemic incidence of metabolic diseases is contributing for the worldwide decline in both, sperm quality and male reproductive health. The biochemical changes induced by lifestyle factors and nutrition in the testis are on spotlight to unveil the mechanisms by which metabolic diseases affect nativity rates and the offspring. There is an intense debate whether worldwide sperm quality is decreasing and the factors that may be responsible for that. Environmental contaminants have arisen as main contributors to the decline on sperm quality. Thus, the molecular mechanisms by which environmental cues alter male reproductive health remain a matter of great interest and are discussed in the thirteenth chapter. The last chapter is dedicated to the biochemical changes in the reproductive function of the aging male. Later parenting is very frequent in modern societies. Nevertheless, the quality and the altered patterns of epigenetics/gene expression in aging sperm remain to be disclosed. Thus, the biochemical changes that occur in testis and sperm and that go along with aging will be on the spotlight for the next decades.

Nowadays, there is a huge investment in reproductive healthcare that is mainly applied in assisted reproductive technologies. However, the long-term effects of these treatments and the causes for male infertility are not cautioned. Overall, this book discusses all the major topics of interest for andrology and mainly presents a focus on the biochemistry of andrology without avoiding the debate on the clinical relevance of the discussed topics. This is a fast growing discipline and thus, there is a great need to educate and prepare students, scientists and physicians for the novel challenges. As scientists working in the field, we felt that most books focused on Andrology lack a strong biochemical view on the topics. As biochemists working in the field for more than a decade, we gathered our team and prepared a book that discusses a large spectrum of topics with high relevance for andrologists all over the world. This book will be valuable for all those working on andrology that aim to understand the magnificent biochemical control of the male reproductive health. Our team had great pleasure preparing this book and we are sure that it will be very useful.

Introduction

Abstract: Andrology has emerged since the 1950’s, when gynecologists started to consistently refer to this word. However, in 1891, there was already an editorial in JAMA suggesting that andrology could evolve to become an important discipline. It was proposed that, as gynecology is a discipline that is focused on the study of genito-urinary female system, andrology could emerge as the discipline focused on the genito-urinary system of males. For many years, this issue was disregarded and there was a long period until the first societies of andrology appeared and establish it in a definitive way. This historical affirmation of andrology as a discipline will be briefly presented, together with a critical view on some aspects that are still a matter of controversy. Reproductive science is a growing discipline that needs economic support from health care systems, institutions responsible for funding research, and training centers. There was never a greater need for trained and well-prepared scientists and physicians to study human reproductive health. Most countries, developed and developing, are witnessing unprecedented rates of people seeking for assisted reproductive technologies. Decreased sperm quality and male reproductive complications are factors that unquestionably contribute to the observed decline in nativity rates. On the other hand, even though females have various contraceptive methods available, men are still limited. This could be improved if more knowledge on sperm formation, maturation and overall testicular physiology arises. In this introductory chapter, we will discuss some challenges for the upcoming years in the field of Andrology.


In 1891, a JAMA editorial referred to andrology as a possible specialty with difficulties in being established, since it was causing some controversy among the genito-urinary surgeons [1]. Nevertheless, it is usually considered that andrology was firstly used with authority by the gynecologist Dr. Harald Siebke from the University of Bonn in 1957 [2]. Although there was great controversy among some physicians, the first step to establish andrology as a valid specialty was taken when the Congress of American Physicians and Surgeons formed the section of Andrology. This decision was welcomed by many researchers and physicians. Andrology established itself as a growing field of research with potential to rapidly develop into a mandatory discipline to evaluate men’s quality of life and health. After this, it developed within the field of dermatovenereology and gained great interest from several important researchers. Validation also came from the German Society for the Study of Fertility and Sterility that acknowledged andrology as part of its activities in 1958. Though, it was only in 1970 that an international committee of andrology was founded in Barcelona. Later, several other associations of andrology were formed, including the Nordic Association of Andrology (1973), the American Association of Andrology (1974), the German Society of Andrology (1975), and the American Society of Andrology (1976). This ended up with the formation of the International Society of Andrology in 1981. The need for a high level of formation highlighted that the training centers should be grouped and thus, in 1992, the European Academy of Andrology was formed to gather and establish the guidelines for the training in andrology at a European level. Then, all the most relevant societies involved in reproductive medicine recognized and gave attention to this specialty, including the European Society of Human Reproduction and Embryology (ESHRE). This resulted in a rapid development of the discipline in the last three decades [3]. Nevertheless, even today, there are few formal board-certified training programs in andrology. There is a parallelism between andrology and gynecology taking in consideration that the latter is dedicated to the study of the genito-urinary system of females, and the former of males. This is of particular relevance because male’s fertility and the study of their reproductive system has always been overlooked when compared with females, in such a way that the term “diseases of women” is used by several physicians to summarize their specialty, while the same is rare in the case of men. Even today, the field of andrology is not widely recognized by non-experts as a clinical discipline or a research field of great interest like others such as gynecology or urology. Thus, public consciousness of the existence and relevance of this discipline is also mandatory. In summary, andrology is a young interdisciplinary specialty that deals with the male, particularly with the physiology and pathophysiology of male reproductive functions and fertility. We may go further and state that the main focus of andrology is to provide a diagnosis and treatment to males with fertility disturbances.

Andrology evolved as a branch of science that deals with male reproduction and its disorders, including erectile dysfunction, infertility and sexual development. In 1969, the first journal “Andrologie” appeared and gave visibility to this emerging field of research. A few years later, the “Andrologia” journal further contributed to the internationalization of the topic. Initially, the works published were mostly focused on the analysis of the ejaculate, particularly sperm morphology. The clinicians, veterinarians and biochemists started to publish important information on the characterization of sperm and the molecular mechanisms responsible for male fertility. Limited analytical methods, at the time, hampered the initial findings, but enormous progress was made in the first years of those journals. With the advent of molecular biology techniques, omics technologies and hormonal knowledge, andrology entered in a new era of findings. We never had so much information and ways to study testicular physiology, hormonal network, sperm physiology, testicular disorders, and the genetics of the individuals, as we have nowadays. It is also important to highlight that andrology emerged as a discipline that is forced to cooperate with others, including urology, dermatology or endocrinology and thus, it relies on a multidisciplinary work. In addition, concerning the fertility of couples and the treatment of childless couples, it is pivotal that andrologists and gynecologists cooperate and work together to solve the problems beyond the use of assisted reproductive technologies. The diagnosis and therapies of couples would greatly benefit from that. Family planning is also another important matter that benefits from the joint work of both specialties. Nowadays, there are several physicians engaged in andrology and thus, universities and research groups focused on this discipline have highly increased in the last decades. In addition, there is a high number of scientists, besides medical doctors, such as biochemists, veterinaries or biologists that focus their research interest in andrology. Training of highly qualified people is still a major need, as well as support from funding agencies to explore new methods of examination and fundamental research in this field. Basic scientists have also greatly contributed to the exponential growth of this discipline, particularly those with strong formation on biochemistry, biology, pharmacology, genetics and molecular biology. This multidisciplinary approach has allowed a rapid advancement in the understanding of the physiology and biochemical events involved in male reproduction, from the hormonal regulation to the genetic mechanisms responsible for those processes [4, 5]. Nevertheless, the translational gap between basic science and clinical practice still hampers some effective developments that could be useful to improve male reproductive health. We are witnessing an unprecedented need for scientists working on reproductive science. In fact, most developed countries present high rates of induced abortion. Notably, the oral contraceptive method was introduced in 1960, and some authors alerted to the fact that the fundamental biochemical research that served as the basis for this

major step in reproductive medicine, was available since the 1920s and 1930s [6]. This clearly highlights that there is a need for a major involvement of basic researchers on translational andrology and andrologists with interest on fundamental research. To encourage both, more funds should be allocated to these areas. In addition, pharmaceutical industry should be more engaged to develop novel strategies to improve the health care of males. The general public and policymakers must be more aware of the need for andrology as an essential discipline, and special funds must be allocated to actively seek for the improvement of men’s health, including the treatment of disorders (i.e. infertility, erectile dysfunction, prostate cancer) and the development of a male contraceptive. In addition, there are several societal challenges that should be considered, including the fact that men are becoming fathers later in life. As the age of father increases, there is a higher risk for miscarriage or disease in the offspring. Another important issue to be considered is the epigenetic information that can be passed along generations [7].

How genetic and environmental factors limit sperm quality and overall male reproductive health should be on spotlight for the next decades. It is of paramount importance to understand those mechanisms and to identify targets to either counteract deleterious effects or to develop a male contraceptive. The pandemic incidence of metabolic diseases and wrong dietary habits are also key factors that are now gaining momentum concerning their effect on the male reproductive health. Thus, physicians, biochemists and basic researchers should also join their efforts to study the mechanisms of action by which those factors may limit male’s fertility.

There is a need for a holistic view of andrology, as an interdisciplinary medical specialty that may evolve even further with a biochemical approach. In addition, the initial problems of the discipline, such as erectile dysfunction or ejaculatory dysfunctions, developed to more dramatic issues in the worldwide trends of ageing male, including neoplastic diseases of the prostate and testis. We may postulate that andrology is still a field with a great margin of progress with the implementation of a multidisciplinary approach. This book aims to contribute to further understand this field of research from a biochemical point of view.

  • Testis Physiology 
  • Basic Aspects of Testicular Cells: Physiology and Function
  • Basic Aspects of Spermatogenesis 
  • Hormonal Control of Male Reproductive Function 
  • Male Puberty: A Triggered Biochemical Event towards Sexual Maturation 
  • Biochemical Events Occurring in the Epididymis 
  • Formation and Biochemistry of Seminal Plasma and Male Accessory Fluids 
  • Functional and Biochemical Aspects of Spermatozoa 
  • Biochemistry Behind the Journey of Spermatozoa Through the Female Reproductive Tract 
  • Testicular Cancer, Erectile Dysfunction and Male Reproductive Health 
  • Metabolic Disorders and Male Reproductive Health 
  • Environmental Cues and Sperm Quality 
  • Biochemical Changes in the Reproductive Function of the Aging Male 



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