Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
Currently Skimming:
4. Biologic Markers of Testicular Function
4. Biologic Markers of Testicular Function
Pages 47-62
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 47... ...
First, the human testis has 14 organization of what will become androgen- recognizable types of germ cells. Second, dependent target tissues in puberty and toxic effects on a specific germ cell might adulthood, the masculinization of the male not be manifested in the semen for alive car at puberty, and the maintenance of growth and function of androgen-dependent organs in the adult.
|
From page 48... ...
The slow decline in the number of motile spermatozoa in the ejaculate was interpreted by the investigators as suggesting that there was no immediate damage to spermatozoa transport or the epididymis. They believed that primarily postspermatogonial germ cells were killed by the AMSA therapy.
|
From page 49... ...
LEYDIG CELLS Leydig cells are the principal source of testosterone in the mammalian male (Ewing and Zirkin, 1983~. Leydig cell growth and differentiated function depend on anterior pituitary production of luteinizing hormone (LH)
|
From page 50... ...
The advantages of measuring the concentration of LH and testosterone in peripheral blood serum of humans or experimental animals are that it directly monitors the gonadotrope and Leydig cell function, respectively, and that repetitive measurements can be obtained for assessing temporal effects of a treatment. Disadvantages of measuring LH and testosterone in peripheral blood are that only small amounts of blood can be collected from small rodents, unless red blood cells are replaced and that, because LH and testosterone production are episodic, several measurements are required.
|
From page 51... ...
, and a careful evaluation will determine whether specific hormones can be measured in urine samples as biologic markers of the functional status of the hypothalamoadenohypophysial-Leydig cell axis in experimental animals and humans. Leydig cells probably have functions other than testosterone production.
|
From page 52... ...
SEMINIFEROUS TUBULES The seminiferous tubules in the adult mammalian testis contain germ cells in various developmental phases and nonproliferating Sertoli cells. The reader is referred to several comprehensive reviews AL4LE REPRODUCTIVE TOXICOLO(;Y (Roosen-Runge, 1969; Clermont, 1972; Ewing et al., 1980; Griswold, 1988)
|
From page 53... ...
Sertoli cells must be involved at least in germ cell division and differentiation, in view of their direct and specialized membrane contact with germ cells, their formation and presumed control of the milieu of the adluminal compartment of the seminiferous tubule via the tight junctions between adjacent Sertoli cells, and their apparent transduction of hormonal signals (e.g., from FSH and testosterone) that are known to regulate spermatogenesis.
|
From page 54... ...
The other three hold considerable promise as biologic markers, because they are specific products of the Sertoli cell, because they probably are secreted into the peripheral blood, and because considerable progress has been made in cloning genes for them. The discovery of ABP (Ritzer.
|
From page 55... ...
Thus, especially in animal species, but even in humans, fertility is unlikely to be a sensitive indicator of toxic insult of spermatogenesis. Therefore, our task is to elucidate biologic markers that reflect the exposure to or effect of toxicants on the number and function of germ cells, from primitive spermatogonia to fully formed spermatozoa.
|
From page 56... ...
An alternative to direct counting of stem cells is to count the stem-dependent cells after a toxic insult. One way to do that is to count the number of repopulating and nonrepopulating seminiferous tubular cross sections in a series of experimental animals killed at different times after treatment with a toxic chemical (Meistrich, 1986~.
|
From page 57... ...
The marker is nonspecific, in that any toxic insult that depletes germ cells causes an increase in FSH production and testosterone and estradiol also partially control FSH production. Markers Requiring Research and Development The application of molecular biology to the study of mammalian testicular differentiation is providing investigators with insights into many of the molecular mechanisms that regulate male germ cell formation.
|
From page 58... ...
Results of biochemical analyses of the differentiating haploid germ cells that transform into the highly polarized spermatozoon suggest that the definition of all the possible sperm-specific molecuA~E REPRODUCTIVE TOXICOLOGY tar markers has only begun. As a result of such studies and the well-characterized sequence of events leading to the formation of spermatozoa, efforts to monitor the effects of toxicants on male germ cells can be based on substantial knowledge and use the numerous DNA probes already available for the mammalian testis to study the mechanism of toxic action of individual chemicals on spermatogenesis.
|
From page 59... ...
The origin of these probes will not pose a problem for application to human DNA. Because DNA probes for homologous genes in humans and other vertebrates share substantial sequence homology, the animal probes can be used to isolate equivalent human sequences from available human cDNA or genomic DNA libraries, and investigators committed to human toxicology studies should seriously consider the direct isolation and characterization of human DNA probes.
|
From page 60... ...
For instance, if the MPl-cDNA probes are used, no MPl-mRNA is detected in testicular exM>llLE REPRODUCTIVE TOXICOLOGY tracts of prepubertal mice up to 20 days old (a time when spermatogenesis has advanced to meiosis) , whereas a 580-nucleotide form of MPl-mRNA is present in the testes of 22-day-old mice (early spermatids are present by day 22)
|
From page 61... ...
It has therefore been difficult to work biochemically with this cell type, and no DNA probes peculiar to spermatogonia have yet been isolated for this critical stage of spermatogenesis. Because genetic alterations in stem cell DNA will produce persistent heritable defects, a major effort needs to be commenced to obtain an armamentarium of DNA probes specific to animal and human testicular stem cells.
|
From page 62... ...
The primary limitations on the application of DNA probe technology to evaluate genomic DNA alterations in spermatozoa are three: DNA probes are available for only a very small portion of the genome; current procedures severely limit the number of probes that can be assayed at one time, thereby restricting the percentage of the genome examined in each analysis; and the DNA from single cells, such as spermatozoa, cannot be analyzed. Theoretically, the limitations can be overcome.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.