Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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23. Conclusions and Recommendations
23. Conclusions and Recommendations
Pages 253-262
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From page 253... ...
Recent research emphasizing cellular and molecular aspects of mammalian developmental and reproductive biology has identified an extensive directory of structural and functional markers. These could be used effectively to define a cause-and-effect relationship in which
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From page 254... ...
At least two qualitative determinations could be used in assessing possible pregnancy complications: appearance of DNA adducts in extraembryonic fetal tissues and immunologic procedures that allow identification of high- risk couples, perhaps before they begin to produce fertilized eggs. Tests should be developed to classify high-risk couples according to the etiology of the problem; some spontaneously aborting women could then be treated according to the pathophysiologic characteristics of the underlying defect.
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From page 255... ...
ASSESSMENTS OF THE STATUS OF SPECIFIC MARKERS RELATED TO PREGNANCY The following recommendations concerning potentially useful biologic markers of exposure and effect during pregnancy represent current knowledge in clinical and basic sciences of reproduction and
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256 TOXICITY DURING PREGI~NCY TABLE 23~1 Biologic Markers Associated with Pregnancy and Possible Reproductive Hamrds Marker Immediately Usable in Large Scale Human Studies Usable in Studies of Selected Individuals Promising for Human Studies; Needs More Animal Studies Development Needed Exposure Markers—Concentrations ofTomcants or Metabolites in: Matemal Blood + Urine + Feces + Hair + Nails Tissue biopsy Endometnum Cervical mucus Uterine washings Fat Conception products Placenta Conception products Chorionic villus sample Placenta at delivery Amnion at delivery Chorion at delivery Umbilical blood Embty - Fetus Conception products Tissue Blood Hair at deliver Nails at delivery Urine at delivery Feces Amniotic fluid Amniotic cells Foreskin + + Effect Markers Matemal Clinical history General health + Reproductive history + Menstrual history + Steroid-LH-FSH concentrations Uterine prolactin Immune status hLA types TLX antigens Histology Vaginal epithelium End am et riu m Cervical mucus Globulin and other protein types Uterine blood flow + + + + + + + + + + + + + + + +
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From page 257... ...
CONCL USIONS AND RECOMMENDS TIONS 257 Immediately Usable in Large~cale Human Studies Usable in Studies of Selected Individuals Promising for Human Studies; Needs More Arsenal Studies Development Needed Placental Placental hormone concentrations: hCG hPL EPF cACrH cTSH PAPP-A Interferon Interleukin I Estradiol Estriol Progesterone Receptor number and affinity for: Bet a-a drenergic Diazepam Glucocorticoids Epidermal growth factor Opiates Somatomedin Testosterone I(DD Binding site number for: IgG-Fc Low-density lipoproteins Retinol binding protein Transcobalamin II Transferrin Concentrations of associated proteins SP1 Alpha-fetoprotein Alkaline phosphatase Transcobalamin I/II/III DNA adduct frequency Metabolic rates of: Nutrients Xenobiotics Transport efficiency of: Nutrient Xenobiotic KaIyotyping Morphometr; Histology of placer." tissues Embryo, Fetus, and Neonate Physical examination + at delivery Apgar or Brazelton scales Presence of dysmorphology + + + + + + + + + + + + + + + + + + +
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From page 258... ...
Table 23-2 lists some biologic markers by the periods during pregnancy for which the marker is informative. The first period comprises any time before conception until the anticipated menstrual period in that cycle (14 days after conception)
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Markers of Effect Before and Around Implantation Success of a pregnancy is established before and around implantation as a consequence of maternal immunologic status and synchronized interaction of the uterine endometrium and the developing embryo. The greatest risk to successful completion of pregnancy occurs during the interval encompassing conception, embryo attachment to the uterine epithelium, and embryo advancement into the differentiating stroma.
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260 TOXICITY DURING PREGNANCY TABLE 23-2 Biologic Markers Associated with Pregnancy and Possible Reproductive Hazards, by Period of Gestation l Up to 14 Days After Conception Useful: hCG Promising: Potential: Organogenesis Useful: Promising: Clinical history Steroid concentrations Blood or urine concentrations EPF TLX HLA types Uterine prolactin concentration Uterine secretions of hormones Uterine secretions of xenobiotics Sonography for size and location hCG Clinical history Hormone concentrations Sonographic measurements: Growth Size Movement Magnetic resonance imaging: Image dysmorphology Identify energy sources using p32 Assess xenobiotic or nutrient concentrations using C~3 Potential: Chorionic villus sampling: Karyotyping Enzyme activity levels and isotypes Localization-metabolism of xenobiotics DNA-adducts Flow-activated sorting During Fetal Growth Period Until Birth Useful: Sonography to assess: Growth Fetal breathing CNS function Dysmorphology Doppler blood flow measurement of: Uterine blood flow Umbilical blood flow Fetal heart rate Biophysical monitoring: Heart rate Amniocentesis to perform: Promising: Karyotyping Xenobiotic analysis Toxicity screen of embryo culture Alpha-fetoprotein Maternal serum-cord to measure concentrations of: CEA Alpha-fetoprotein HPL Xenobiotics Fetal cord sampling Fetos~copy Flow-activated sorting
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From page 261... ...
Magnetic resonance imaging is being used increasingly to assess structure and to determine substance localization within fetal tissues. As molecular probes specific for events in organ development are developed, markers of toxicity of specific toxicants might become evident.
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From page 262... ...
Fetal blood samples and tissue biopsies can be obtained with fetoscopy, and amnio centesis provides amniotic fluid and cells for evaluation. The combination of chori onic villus sampling and molecular probes for specific genetic disorders can be used to assess the capability of the conceptus to respond to environmental insult.
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