Embryo, and Fetus

Humphrey T. (1940). The development of the olfactory and accessory olfactory formation in human embryos and fetuses. J Comp Neurol 73, 431-468. 

Kreutzer E.W. and Jafek B.W. (1980). The vomeronasal organ of Jacobson in the human embryo and fetus. Otol HeadNeck Surg 88, 119-123. 

Stather JW, Harrison JD, Kendall GM. 1992. Radiation doses to the embryo and fetus following intakes of radionuclides by the mother. Radiat Prot Dosim 41(2/4) 111-118. 

Review of NCRP Radiation Dose Limit for Embryo and Fetus... 

A burning issue is the ethics of obtaining pluripotent stem cells from embryos and fetuses. The US government has acted on this issue and declared that federal funds for stem cell research have to meet certain criteria. It requires that funding will only be provided to research with stem cells obtained before August 9, 2001, as a cut-off date to limit research to preexisting stem cells. Refer to Section 11.7 for an ethical debate on stem cells. 

So far the toxicologist has not made inquiries regarding a number of potentially important questions. Can the chemical harm a developing embryo and fetus, perhaps producing birth defects Can the chemical reduce male or female fertility, or otherwise impair reproduction Can... 

An area of emerging importance is developmental toxicity. Here we are concerned about the effect of the chemical on the developing embryo and fetus (exposures received in utero), and on the further development of the infant and child subsequent to birth, at which time chemical exposure may cease, or may continue to weaning because the chemical received by the mother is transferred to her milk. Or it may continue throughout life because there are sources of the chemical in addition to that supplied by the mother because of her exposure. 

Many drugs and pesticides readily cross the placenta to reach significant concentrations in fetal plasma. However, other chemicals cross the placenta less readily and their concentrations are lower in the fetal plasma than maternal plasma (6). In the case of the latter chemicals, the placenta may be exposed to higher concentrations of the chemical than the embryo. Thus, any adverse effects of the drugs on development may result from direct effects to the embryo and fetus or from indirect effects through altered placental function (7). 

The embryo-fetal development study aims to detect adverse effects on pregnant females (i.e., maternal toxicity) and on the development of embryos and fetuses (i.e., embryo-fetal death, altered growth, and structural changes) consequent to exposure of the female during organogenesis. 

Chemicals produce adverse effects in the developing embryo and fetus by a variety of mechanisms (Bishop Kimmel, 1997). These may involve interactions of the exogenous agent with endogenous receptors, adduction of reactive intermediates to DNA or proteins, lipid peroxidation, enzyme inhibition, cell membrane alterations and others (US NRC, 2000). 

The uterus and its contents should also be examined prior to parturition to determine the number of live young and dead embryos and fetuses. The sum of these values equals the number of implantation sites. If the corpora lutea are counted (this may be very difficult in mice), then the difference between the number of implants and the number of corpora lutea indicates the extent of preimplantation loss. However, this is not necessarily accurate if the dam is dosed at the time of implantation, because it is possible to interfere with implantation to the extent that no visible sign remains. The difference between the total number of implants and the number of live implants gives the postimplantation loss, subject to the same caution as above. If there are no signs of implantation, the uterus can be stained with ammonium sulfide (Saleweski, 1964), which reveals completely resorbed implantation sites. The difficulty of distinguishing between preimplantation loss and very early postnatal implantation loss emphasizes the necessity of evaluating both parameters. 

There is clear evidence from many different sources that the metabolism of compounds may be involved in their teratogenic effects, as will be seen in the final chapter in the discussion of thalidomide and diphenylhydantoin teratogenicity. The embryo and fetus of some species clearly have metabolic activity toward foreign compounds, which may be inducible by other foreign compounds. 

There are four outcomes of this interference death, malformations, functional deficiencies, and growth retardation. Because the development of the embryo and fetus involves a sequence of events, many chemicals and other agents can interfere with this, leading to one or more of the above four manifestations. There will be many mechanisms underlying the response, therefore such as interference with normal biochemical pathways as well as cytotoxicity. 

Nau H, Bass R. 1981. Transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the mouse embryo and fetus. Toxicology 20 299-308. 

Several studies indicate that different methods cause adverse effects to embryonic and fetal tissues and eventually lead to the development of teratogenic effects. Metals are omnipresent in the living environment. A variety of anthropogenic activities (e.g., smelting metallic ore, industrial and metal fabrication, commercial application, burning of fossil fuels) have caused adverse effects to the developing fetus. In fact, notorious elements, such as cadmium, lead, and mercury, have been associated with injury and malformation to the growing embryo and fetus of animals and humans.65... 

These studies are conducted in order to detect adverse effects on the pregnant female and the development of the embryo and fetus exposed in utero. Basically the period between implantation and closure of the hard palate is being investigated. In the NFIP, however, only the period between postimplantation... 

The aim of this study, often called teratogenicity study , is to detect adverse effects of the test compound on the pregnant female and on the development of the embryo and fetus, from implantation of the blastocyte to closure of the hard palate. Adverse effects to be assessed are enhanced toxicity to the pregnant organism in relation to the non-pregnant, death of the embryo or fetus, altered growth and structural changes in the conceptus. 

Zecevic N, Verney C (1995) Development of the catecholamine neurons in human embryos and fetuses, with special emphasis on the innervation of the cerebral cortex. J Comp Neurol 357 509-535. 

Today, the use of embryonic stem cells for any purpose arouses strong emotional responses, because of its relation to the grave moral issues associated with abortion, and the status of human embryos and fetuses. The questions that follow have provoked a considerable amount of controversy. 

For the purposes of this chapter, the term reproduction will be used primarily in reference to vertebrate species of animals (especially mammals) and will be inclusive of development (Figure 36.1), which is sometimes treated as a separate topic in toxicology texts. This particular chapter emphasizes what is currently known about the adverse effects of known chemical warfare agents and selected environmental contaminants on male and female reproductive function, as well as xenobiotic-induced effects on the growth, maturation, and sexual differentiation of the embryo and fetus. Endocrine disruption is an extremely common mechanism of action for xenobiotics associated with impaired reproductive function and will be discussed along... 

The embryo and fetus, without a developed blood-brain barrier and with only radimentary DNA repair mechanisms and hepatic detoxifying and metabolizing capabilities, are especially susceptible, as compared to adults, to the adverse effects of low-level exposures to xenobiotics (Evans, 2007 ... 

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