Epigenetics and Reproductive Health

Trygve Tollefsbol

• Publisher: Academic Press
• Year: 2020
• Print ISBN: 9780128197530
• eBook ISBN: 9780128197547
• Topic: Medicine
• Subtopic: Genetics in Medicine

Epigenetics and Reproductive Health, a new volume in the Translational Epigenetics series, provides a thorough overview and discussion of epigenetics in reproduction and implications for reproductive medicine. Twenty international researchers discuss epigenetic mechanisms operating during the formation of male and female gametes, fertilization and subsequent embryo and placental development, particularly in mammals and transgenerational epigenetic inheritance. This volume also addresses aberrant epigenetic changes influencing male and female infertility, pregnancy related disorders, and those potentially linked to therapeutic manipulations and assisted reproductive technologies. Emphasis is placed on identifying biomarkers for early detection of aberrant epigenetic mechanisms.Later chapters examine the possibility of correcting these epigenetic dysfunctions, as well as current challenges and next steps in research, enabling new translational discoveries and efforts towards developing therapeutics.- Thoroughly examines the influence of aberrant epigenetics during gametogenesis and embryogenesis, affecting parents, gametes and embryos, offspring and future generations- Explores health outcomes for reproductive senescence, endocrine disruption, testicular cancer, prostrate cancer, breast cancer, ovarian, cancer, endometrial cancer and cervical cancers- Features chapter contributions from international researchers in the field

Section IV

Reproductive cancer and epigenetics

Outline

Chapter 14. Testicular and prostate cancers

Chapter 15. Emerging patterns and implications of breast cancer epigenetics: an update of the current knowledge

Chapter 16. Ovarian & endometrial cancers

Chapter 17. Epigenetic aberrations in cervical cancer

Chapter 14: Testicular and prostate cancers

Eva Tvrdá Department of Animal Physiology, Faculty of Biotechnology and Food Sciences, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, Nitra, Slovakia

Abstract

Male reproductive malignancies represent a significant health concern, with an ever-increasing incidence worldwide. Cancer is a disease caused and fueled by the interaction of genetic and epigenetic mechanisms involved in the regulation of cell growth and behavior. Recently, numerous reports have focused on the epigenetical aspect of testicular and prostate cancer. As such, the aim of this chapter is to provide current information on the testicular and prostate tumorigenesis with an emphasis on epigenetics. Understanding the epigenetic mechanisms such as DNA methylation and histone modifications together with microRNAs in healthy tissues, precancerous lesions as well as malignant specimens may provide the base for the discovery of novel biomarkers for cancer prediction, diagnosis, prognosis, and treatment response. Furthermore, numerous epigenetic alterations represent a promising target for new therapeutic strategies and treatment management for patients with male reproductive cancers.

Keywords

Testicular cancer; Prostate cancer; Epigenetics; DNA methylation; Hisotne modification; miRNAs

Introduction

Originally, it was believed that cancer was primarily a genetic disorder. Nowadays, however, it is known that malignancies originate as a result of an interplay of genetic factors and abnormal epigenetic events [1]. While genetic abnormalities are directly associated with changes in the DNA sequence, epigenetic alterations represent a consequence of an abnormal chromatin structure and gene expression, which will be transmitted to further generations without the actual changes in the DNA sequence. What is more, recent evidence suggests that the epigenetic machinery may actually provoke genetic alterations [1,2].

Epigenetic remodeling in malignancies may have a significant impact on multiple gens and cellular pathways in a non-random fashion, leading to the eventual accumulation of genetic alterations over the course of cancer initiation and progression [1]. Understanding the epigenetic principles in health and disease is essential for a better insight of neoplastic growth, development and resistance to treatment as well as for the development of new prevention, control and therapeutical strategies [2].

Male reproductive cancers

Testicular cancer

While testicular cancer (TC) is considered to be a relatively uncommon disease with an incidence of 10 in 100,000 males [3,4], it is the most prevalent neoplasm diagnosed in young men of 15–40 years, which is considered the most productive age [5]. The most accepted hypothesis explaining this association suggests a burst of hormones typical for adolescence, triggering carcinoma in situ (CIS) cells, which have the potential to proliferate into neoplasms [3,6].

The incidence of TC changes significantly depending on the geographical area: the occurrence rates are high in Scandinavia and Western Europe, USA, Canada and Australia, while the lowest incidence has been observed in Southern Europe, Central and South America as well as in Asia and Africa [7]. While the incidence of TC has significantly increased over the past decades, particularly in Caucasian men, if diagnosed early, the survival rate is close to 99% [8].

Most TCs are of germ cell origin [5], with testicular germ cell tumors (GCTs) representing about 95% of all testicular malignancies. GCTs may be further divided into seminomas and non-seminomas, with each constituting approximately 50% of GCTs. In the meantime, approximately 15% of GCT patients are diagnosed with both types [9]. Seminomas and non-seminomas have different histological and biological properties as well as a metastatic potential [4].

Seminomas arise from the testicular germinal epithelium, most likely from primordial germ cells considered to be progenitors of spermatozoa [9]. Seminomas normally occur in later stages of life (fourth to fifth decade), and comprise a uniform population of cancerous primordial cells. The tumor has a consistent histological aspect, which is why seminomas are highly suitable to investigate and understand testicular neoplasia-associated alterations in gene expression [8]. Seminomas are generally more treatable with surgery, radiation or chemotherapy [7,9].

Non-seminomas represent a heterogenous group of different germ cell tumors such as teratomas, yolk sac tumors, embryonal carcinomas and choriocarcinomas [9]. These tumors occur more frequently among young men (second to third decade), and are generally more aggressive with heterogenous histological features [6]. Non-seminomas have with a higher predisposition for an early spread and poorer prognosis, particularly in advanced stages. A traditional option for nonseminoma treatment is chemotherapy because of their lower sensitivity to radiation [10].

A small portion of testicular neoplasms represent stromal tumors such as Sertoli and Leydig cell tumors, and other unusual or poorly characterized malignancies [7]. These neoplasms are usually benign and treated by surgery, however they become resistant to conventional therapy as they metastasize [11].

Both genetic as well as environmental factors play essential roles in the genesis of TC. Exposure to pesticides and non-steroidal estrogens is the most prevalent environmental factor contributing to TC development [12]. Strong correlations have been observed between increased TC risk and maternal smoking or bleeding during pregnancy as well as premature birth [13]. Among the risk factors associated with the onset of TC, cryptorchidism, hypospadias, family or personal history of TC, congenital abnormalities of the testicles, penis or kidneys as well as infertility are the most prominent [3,14–16].

In testicular malignancies, serum tumor markers such as alpha-fetopr...

Table of contents

• Cover image
• Title page
• Table of Contents
• Translational Epigenetics Series
• Dedication
• Copyright
• Contributors
• Acknowledgment
• Introduction to epigenetics: basic concepts and advancements in the field
• Section I. Spermatogenesis, oogenesis and fertility
• Section II. Pregnancy/ developmental/ placental epigenetics
• Section III. Epigenetic e lifestyle, aging and environmental influence
• Section IV. Reproductive cancer and epigenetics
• Section V. Epigenetics in diagnosis, prognosis and therapy
• Index