Fertility and Chromosome Pairing

Christopher Bob Gillies

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781000141818
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

This book discusses the nature of meiotic chromosome pairing effects which may play a role in the determination of fertility. In particular, data and illustrations from the application of recently developed electron microscopic spreading techniques will allow researchers in related fields to come to grips with the recent advances in the cytogenetics of meiotic chromosome pairing behavior. Topics dealt with include meiotic and synaptonemal complex behavior in humans and mice with a variety of chromosomal and genetic abnormalities, sex chromosome pairing in mammals and birds, the significance for fertility or pairing in mammals and birds, the significance for fertility of XY pairing and crossing over, the effects of hybridity on pairing and fertility in plants, and the genetic control of synaptonemal complex formation and crossing over in polyploids. This is a timely reference book for graduate level medical and veterinary students, and scientists in the field of genetics and cell biology.

Chapter 1

HETEROLOGOUS PAIRING AND FERTILITY IN HUMANS

R. M. Speed

TABLE OF CONTENTS

I. Introduction

II. Homologous Vs. Heterologous Pairing in Humans

III. Normal Male and Female Meiosis

A. The Timing of Meiotic Progression

B. Human Meiosis at the Light-Microscopic Level

1. Male

2. Female

C. Human Meiosis at the Electron-Microscopic Level

1. Male

2. Female

IV. Effects of Trisomies and Sex Chromosome Aneuploidy

V. Translocations and Fertility

A. Autosome-Sex Chromosome Translocations

B. Autosome-Autosome Translocations

1. Reciprocal

2. Robertsonian Translocations

VI. Inversions, Synaptic Adjustment, and Fertility

VII. Genetic Control of Asynapsis and Desynapsis

References

“In all this work we have to be aware that meiosis works with chromosomes which always have the two functions of accomplishing evolution and of implementing its results in heredity. In consequence, the adaption of meiosis is perpetually imperfect.”¹

I. INTRODUCTION

Fertility in mammals, of which humans are perhaps an unique example, has been of interest since primitive times. On a global scale, it would appear that man has been highly successful in this capacity, with a doubling of the world population expected between the present time and the first decade of the next century. Indeed, until recently, the main problem has been the control of fertility. With technological advances in both the understanding of the hormonal control of reproduction and in methods of contraception, unwanted fertility has virtually disappeared in the developed countries.² As a result of the apparent ease of such fertility control, it is perhaps not surprising that couples now believe that there are difficulties in fertility if a child cannot be conceived within a short period of time.

On an individual basis, about one in ten couples will encounter problems of conception, with varying levels of accompanying emotional trauma.³ In 60 to 80% of such couples, factors in either the male or female partner will be the cause of the fertility problem. A combination of events will account for the remainder.

In the context of this chapter, the problems of fertility in humans will be limited to an examination of various aspects of the meiotic process. This is a vital stage in the system by which normal and/or abnormal gametogenesis occurs in humans, leading to the production of male and female germ cells. In particular, the study of the pairing process between homologous human chromosomes at the prophase stage of meiosis will be examined for any subsequent effects on fertility.

Historically, the investigation of the human male germ cell system has predominated due to the more ready availability of testicular material from adult males attending infertility clinics. Since Ford and Hamerton in 1956⁴ employed a squash technique to establish that male spermatocytes contained 23 bivalents, subsequent development of air-drying methods⁵ has allowed advances in the analysis of homolog synapsis and disjunction at the light-microscopic (LM) level. More recently, the modification of the Counce and Meyer⁶ surface-spreading technique to human material has enabled detailed analysis with both the light⁷ and electron microscopes⁸ of meiotic pairing at the synaptonemal complex (SC) level. Complementary observations on serial sections of human germ cells^9,10,11 have also provided much detailed information on SC pairing at the electron-microscopic (EM) level in both sexes. The structure of the SC in organisms as diverse as fungi and man is remarkably conserved and its relationship with the meiotic process is well established.^12,13 The origins of the SC at the earliest stages of meiotic prophase and its absence in situations where crossing over is not evident, as in Drosophila males,¹⁴ suggest its involvement in both homolog synapsis and recombinational events, both being of critical importance to eventual germ cell development in humans.

II. HOMOLOGOUS VS. HETEROLOGOUS PAIRING IN HUMANS

In reality, very little experimental meiotic work of any nature has been performed on humans due to the obvious ethical problems. The majority of studies of chromosome pairing, the structure and function of the SC, and their relationship to germ cell maturation and fertility have occurred in plant and animal species. Data from rodent¹⁵ and primate¹⁶ sources will, however, be of major interest in defining general concepts and models applicable to humans. Chromosomally normal or abnormal situations, either created experimentally or occurring naturally in such animal systems, are open to extensive investigation and will be described in detail in other chapters. Nevertheless, a brief description of pairing at the chromosome/SC level is appropriate at this point to clarify the nature of heterologous pairing.

Chromosome pairing begins in most species with the rough alignment (300 nm apart) of the lateral elements of the homologous chromosomes.¹⁷ Only when lateral elements are separated by approximately 100 nm does the SC begin to form. Initiation points may be numerous, as in plant species, or be almost strictly telomeric, as in the human oocyte. Normally, only homologs will initiate synapsis at meiotic prophase (homologous pairing), but numerous examples now exist of SCs that can form between chromosomes or segments of chromosomes that are nonhomologous in genetic content (heterologous pairing).^18,19,20 Heterologous pairing may also develop at prophase, in chromosomal rearrangements such as duplications or inversions,²¹ and has been termed by Moses et al.²² “synaptic adjustment”. The fact that such SCs appear of normal dimensions and structure suggests that the SC, per se, is not the mechanism of genetic exchange, as such heterologous pairing in plant haploid species,²³ does not lead to chiasma formation or crossing over.

It is generally held that recombination will only take place when DNA sequences of strict homology are brought into register either in the central region of the SC or within the bulk of the chromatin surrounding the SC. More than 99% of the chromosomal DNA remains outside the confines of the SC, it being calculated for Neurospora¹² that t...

Table of contents

• Cover
• Title Page
• Copyright Page
• Table of Contents
• Contributors
• Preface
• The Editor
• Chapter 1 Heterologous Pairing and Fertility in Humans
• Chapter 2 Chromosome Pairing and Fertility in Mice
• Chapter 3 Sex Chromosome Pairing and Fertility in the Heterogametic Sex of Mammals and Birds
• Chapter 4 Chromosome Pairing and Fertility in Plant Hybrids
• Chapter 5 Chromosome Pairing and Fertility in Polyploids
• Index