Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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7. Biologic Markers of Human Male Reproductive Health and Physiologic Damage
7. Biologic Markers of Human Male Reproductive Health and Physiologic Damage
Pages 83-106
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From page 83... ...
The development and validation of markers of human male reproductive health require a multidisciplinary approach that includes basic research in animal and human reproductive biology, engineering and statistical development of automated and quantitative procedures, clinical studies of human factors that affect variation and of the predictive value of individual markers, and epidemiologic studies of populations exposed to xenobiotic agents. This chapter begins with a short review of the kinds of epidemiologic studies that have been performed to evaluate fertility effects of human males exposed to reproductive toxicants.
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From page 84... ...
EPIDEMIOLOGIC STUDIES OF HUMAN SPERM PRODUCTION AND FERTILITY Interview data, medical records, and demographic birth records, as well as semen and blood hormone analyses have been used to evaluate the effects of radiation or chemicals on human fertility and spermatogenesis. Although surveys are not generally considered markers of reproductive health, they are a means of evaluating the fertility status of well-characterized groups and thus provide important benchmarks in the development and validation of markers related to fertility.
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From page 85... ...
Further work and additional approaches are needed to improve the quantitation of surveybased indicators of human fertility status. Markers of Early Pregnancy Early pregnancy monitoring may provide a very sensitive method for measuring malemediated effects on fertility and pregnancy.
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From page 86... ...
~ , HUMAN SPERMATOGENESIS AND DEVELOPMENT OF SEMEN-BASED MARKERS OF MALE REPRODUCTIVE HEALTH Human sperm production is unique among animals in several ways: · In most animals (laboratory, as well as domestic) , sperm are produced in great excess over what is needed for adequate fertility.
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From page 87... ...
Three applications of semen markers have been proposed: as markers of sperm production and function, as indicators of fertility status, and as indicators of exposure to a reproductive toxin. In this chapter, we distinguish among these three applications because we still lack the data to understand the quantitative relationship among them.
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From page 88... ...
Also listed are new research concepts based on modern cellular, molecular, and recombinant DNA techniques that promise the next generation of biologic markers of human male reproductive health. For all markers, baseline data in normal individuals usually are considered prerequisite for detecting abnormal events and for determining the sample sizes required to detect changes.
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From page 89... ...
, but a similar relationship has not been established for human sperm. As Marker of Fertility Status There is little agreement about the specific relationship between sperm number and fertility status, nor is there agreement on whether total number per ejaculate or sperm concentration (number per ml)
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From page 90... ...
and all semen studies of male reproductive effects of occupational exposure surveyed included it. Exposure to any of 57 agents led to detrimental effects on human sperm production.
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From page 91... ...
However, the problems associated with visually determined sperm structure remain a major impediment to large-scale evaluation of the utility of sperm structure as a marker of male reproductive health, and further work is needed to automate these measures. As Marker of the Quality of Sperm Production Sperm structure is a measure of the quality of sperm produced by the testis and of alterations occurring in the efferent ducts and accessory glands.
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From page 92... ...
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From page 93... ...
As Marker of Fertility Status Evidence from both animals and men links increased proportions of abnormal sperm forms with reduced fertility. Human sperm with abnormal head shapes are less motile in vitro than normally shaped sperm, and sperm structure has been correlated with poor hamster-egg penetration (Shalgi et al., 1985~.
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From page 94... ...
Other Factors That Affect Sperm Structure As in other species, human sperm structure is relatively unaffected by abstinence time and several of the technical factors that influence sperm concentration and motility (Amann, 1981~. However, sperm structure is sensitive to testicular temperature.
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From page 95... ...
Defects in sperm structure and motility might be correlated, inasmuch as abnormally shaped sperm have poorer sperm motility than do normally shaped sperm (Katz et al., 1982~. As Marker of Fertility Status The importance of sperm motility in fertility has been well established; numerous studies have demonstrated a correlation between motility and fertility (Freund, 1968; Eliasson, 1975; Hargreave and Etton, 95 1983)
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From page 96... ...
. AL4LE REPRODUCTIVE TOXICOLOGY SPERM FUNCTION Sperm number, structure, and, to some extent, motility measure the physical aspects of human sperm, but indicate little about sperm function (i.e., ability to travel the female tract and to fertilize the ovum)
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From page 97... ...
The susceptibility of ejaculated human sperm nuclei to these agents in vitro might be indicative of the extent of chromatin condensation or nuclear protein cross-linkage. However, that has not been confirmed experimentally.
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From page 98... ...
that have promise of yielding semen-based markers of male reproductive health. Most are still too early in their development to evaluate their utility (1)
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From page 99... ...
Extensive validation is needed before their utility can be thoroughly evaluated. Quantitative Sperm Structure As with sperm motility, subjectivity plagued all attempts at interlaboratory comparisons of visual sperm structure assessments (Freund, 1966~.
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From page 100... ...
However, there are several factors that should be considered in the application of automated methods for any sperm parameter, not limited to sperm motility or structure: MALE REPRODUCTIVE TOXICOLOGY 1. Automated methods do not in themselves circumvent the fundamental problems of semen collection, handling, and preparation that especially affect sperm motility.
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From page 101... ...
Immunologic reagents can be used to investigate the molecular arrangement of both surface and internal components of human sperm, and they provide an approach for elucidating male reproductive abnormalities on a biochemical and molecular level. This section is organized by sperm components and well as surface domains (acrosome, tail and midpiece, and nucleus)
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From page 102... ...
MALE REPRODUCTIVE TOXICOLOGY Additional changes take place in the plasma membrane as sperm undergo capacitation in the female reproductive tract. That process must occur if sperm are to complete the acrosome reaction and fertilize the ovum.
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From page 103... ...
These studies can be initiated with antibodies that are now available, but larger numbers of antibodies to rodent and human sperm should be prepared specifically for this purpose. If toxic agents are found to have detectable effects on sperm surface domains in experimental animals, monoclonal antibodies can probably be used for detecting toxic effects on the human male reproductive system.
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From page 104... ...
Such methods have not yet been applied to semen. SEMEN MARKERS OF SERTOLI CELL AND LEYDIG CELL FUNCTION Semen provides a natural window for evaluating retrospectively the function of the major somatic cells that support sperm production: Sertoli and Leydig cells, for evaluating retrospectively some aspects of epididymal function, and for evaluating prostatic and seminal vesicle function.
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From page 105... ...
nologies, such as cellular staging under Although chromosome-specific repetitive the microscope and antibodies against DNA probes have been used to assess the spermatogenic proteins and other cell ploidy of individual cells, methods are markers, recombinant probes could be use- not yet sensitive enough to detect unique ful for determining whether transcription sequences in single cells. is altered in infertile men and, if so, what In spite of present limitations, re search and development of recombinant DNA probes for spermatogenic genes are progressing rapidly, and they are expected to have broad applications for assessing male reproductive health.
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