Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
Currently Skimming:
20. Cell Biology: Identifying Biologic Markers Expressed during Early Pregnancy
20. Cell Biology: Identifying Biologic Markers Expressed during Early Pregnancy
Pages 223-240
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 223... ...
In this section, many more potential markers are discussed, including cellular differentiation, diffusible cellular products, and additional hormonal concentration changes. The markers discussed here will lead to better understanding of the biologic processes and possible mechanisms of toxic action.
|
From page 224... ...
No specific or reliable markers of xenobiotic agents can be correlated with any cellular or molecular events of early mammalian development. Some data point to adverse influences of a variety of toxic agents during early development (Dixon, 1985~; however, the data were derived from studies that were not stringently designed or executed and often were evaluated retrospectively.
|
From page 225... ...
To interpret specific cell-to-cell interaction during implantation events, homogeneous populations of individual cell types involved directly in implantation—i.e., endometrial epithelial and stromal cells, blastocyst trophectoderm and ectoplacental cone cells, and trophoblast giant cells-are isolated. The cell populations can be cultured in vitro so that biochemical mechanisms that regulate their differentiation and interactions can be studied (McCormack and Glasser, 1980; Glasser and McCormack, 1981; Scares et al., 1985; Glasser and Julian, 1986; Glasser et al., 1987b)
|
From page 226... ...
Analyses of human endometrial washings have not revealed large concentrations TABLE 20 1 Putative Biologic Markers to Assess Status of Uterine Epithelial Cells Cellular or Developmental Stage Biologic Marker Comments Proliferation Postmitosis Cell number; mitotic index; labeling index Short-term biosynthetic and metabolic index; profiles of apical versus basal cell surface and secretory proteins/glyco proteins Long-term biosynthetic and metabolic index; differen tial response to steroid hormones; differential trafficking of apical versus basal cell surfaces and secretory proteins/glyco proteins Preimplantation Timing of final stages of differentiation; protein/ glycoprotein profiles of apical versus basal surface secretions; timing of rising titers of progesterone and estrogen; differential receptor response Implantation Biochemical index of terminal differentiation; different changes in ster oid hormone receptors; specific early pregnancy factors These markers assess mitogenic response of uterine epithelial cells These markers evaluate physiochemical and biologic responses to regulatory factors (hormones, growth factors) ; can be used to evaluate analogues, congeners (phytoestrogens, catechol E)
|
From page 227... ...
have shown that proteins are secreted throughout the proliferative and secretory phases of the cycle, and their concentrations are lower after ovulation. That is in accord with 227 Not well studied These markers describe responsiveness of cells to steroids; not sensitive to dec~duogen~c stimuli; uterine stromal growth factors not well studied These markers assess uterine sensitivity These markers describe stromal component of receptive uterus the finding of lower fluid volume in the secretory phase (Clemetson et al., 1973~.
|
From page 228... ...
, but only 1824 hours for species with short preimplantation periods (Glasser and McCormack, Webb and Glasser, 1984~. Studies of uterine secretions have been unrewarding in demonstrating a regulatory role for some proteins or in suggesting a cause-and-effect relationship that might make the marker useful to detect specific effects.
|
From page 229... ...
Accessibility to the basal secretory compartment also will permit research on the influence of xenobiotic agents on secretions from epithelial cells or on the effect of secretions on the morphologic and functional differentiation of uterine stromal cells. Studies probably will not yield useful markers in the immediate future, but they will determine whether cell-to-cell communication might be subject to toxic effects.
|
From page 230... ...
is a separate hormone discrete from growth hormone and that amniotic fluid contains extremely high concentrations of immunoreactive hPRL. Specific functions of hPRL in the female include regulation of postpartum lactation in mammary glands, reproductive cycle regulation, pregnancy maintenance, and embryonic growth and development.
|
From page 231... ...
When trophoblast cells lose contact with the inner cell mass or attach to the uterine epithelium, they lose their ability to divide. The trophoblast cells cease division and become giant cells, which have more DNA than other cells (Ilgren, 1983~.
|
From page 232... ...
These markers describe increasing complexity and cleavage stages of trophectoderm differentiation Concentration of early Role of these factors still unclear; existence is not pregnancy factors confirmed in all species Late blastocyst Loss of zone pellucida This marker describes time of hatch and changes in hatching biochemistry of zone pellucida Recognition Expression of trophec- These markers describe immunologic response to embryo; toderm recognition can identify implantation defects antigens Attachment Presence of specific lectin These markers assess implantation and postrecognition receptors and oligonucleo- attachment of trophectoderm and uterine epithelium; tide acceptors; changes in changes suggest reorganization of trophectoderm cell surface and secretory surface proteins, and glycocon jugates; cytokeratin expression Cessation of Decrease in mitotic This marker identifies effect of mitosis-inh~iting factors mitosis labeling index in mural in initiating differentiation trophectoderm followed by polar trophectoderm Binucleation Proportion of cells with 2n chromosomes; increase in nuclear and cytoplasmic areas These markers assess endocycles and role of DNA in sensitivity
|
From page 233... ...
) These are cell lineage markers for trophoblast giant cells; simple epithelial cell type not found in inner cell mass; markers also assess role of cytoskeleton in differentiation; changes in actin and tubulin not well studied, but do not appear to be specific responses These markers assess establishment of trophoblast-uterine relationship; the role of these factors is not well defied This marker assesses fetal growth Role of these factors in organogenesis and fetal growth unknown These markers assess sensitivity of differentiation to regulation by Intracellular environment; specific enzymes not well studied; role of enzymes might be secondary These markers can be used to study factors that initiate up and down regulation of steroids and explore possible autocrine and paracrine regulation; Reimplantation synthesis and secretion have been validated only in pig, cow, and sheep; postimplantation validated in many species; role not well understood These markers assess differentiation secretion of human cytotrophoblast to syn~tiotrophoblast These measurements have been described, but roles are not adequately defined These markers assess differentiation of trophoblast giant cells; PL'1 and PL'2 are under different regulatory mechanisms the DNA increase occurs in the nucleus via endomitotic and endoreduplicative mechanisms (Nagl, 1978; Ilgren, 1983~.
|
From page 234... ...
In the presence of this great pool of maternal plasma progesterone, no role has been identified for progesterone, estradiol, or testosterone contributed by the trophoblast cell. Trophoblast progesterone might have a paracrine role in ontogeny of decidual cell differentiation or an endocrine role in trophoblast regulation of its estradiol receptor (McCormack and Glasser, 1978)
|
From page 235... ...
In the human, PLs are produced by the syncytiotrophoblast (Watkins, 1978~; in sheep, by the trophoblast binucleate cells (Martal et al., 1977; Watkins and Reddy, 1980; Wooding, 1981~; and in rats, by the TGCs (McCormack and Glasser, 1980; Soares et al., 1985~. These PL secretory cells differentiate from readily identifiable precursor cell populationshuman cytotrophoblasts (Enders, 1965)
|
From page 236... ...
No specific function has been assigned to any of the proteins of the various cytokeratin gene families, but these additional landmarks might be important in monitoring functional and morphologic differentiation of specialized cells (e.g., ectoplacental cone cells and other stem or precursor cell populations) (Venetianer et al., 1983~.
|
From page 237... ...
, they lose their ability to divide, and they become giant cells with nuclear DNA contents greater than 4 c. Very little information has been developed since the adventofrecombinantDNA methods regarding the organization of the TGC genome or gene expression of genomic DNA, which can increase from 2 to 1,024 c.
|
From page 238... ...
TOXICITY DURING PREGNANCY Decrease in hCG titers signals interruption of pregnancy, but does not identify cause or tissue site of initial damage. The earliest measurement of complete hCG depends on differentiation of enough intermediate and terminal syncytiotrophoblast cells to produce hCG that can be detected with the assay.
|
From page 239... ...
An injury to trophoblast cells that prevents normal expression of hCG would interfere with early events involved in establishing the placenta and also interfere with hPL expression. However, the sensitivities of hPL and hCG genes and their mRNAs to particular xenobiotic agents could be different, and hPL and hCG gene products should be monitored.
|
From page 240... ...
Endometnum; decidua; maternal Liver Local immune and coagulation reactions Binds small molecules molecules Number of synthetic units; changes in blood flow, ~port, delivegr, steroids; growth factors Not known Estrogen and progesterone; mar represent maternal red pponse to pregnancy Does not include endometnal surface and secretory proteins and ~ycoconjugates tion, or the period before or around implantation (Billington, 1985~. The questions of source and function of these proteins might be resolved in part through the study of differentiation of the human trophoblast cell in culture.
|
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.