Embryonic death

Aneuploidy in live births and abortions arises from aneuploid gametes during germ cell meiosis. Trisomy or monosomy of large chromosomes leads to early embryonic death. Trisomy of the smaller chromosomes allows survival but is detrimental to the health of an affected person, for example, Down s syndrome (trisomy 21), Patau syndrome (trisomy 13) and Edward s syndrome (trisomy 18). Sex chromosome trisomies (Klinefelter s and XXX syndromes) and the sex chromosome monosomy (XO), known as Turner s syndrome, are also compatible with survival. 

J. B., Wei, N. Disruption of the COP9 signalosome Csn2 subunit in mice causes deficient cell proliferation, accumulation of p53 and cyclin E, and early embryonic death. Mol. Cell. Biol. 2003, 23, 6790-6797. 

Steroidal alkaloids found in the Filiaceae family, primarily Veratrum and Zygadenus, have been responsible for large losses in livestock. Fluman and livestock deaths have occurred from accidental ingestion of death camas (Panter et al., 1987). Thousands of lambs have died or been destroyed because of Veratrum-indvLCQd malformations, most notably a craniofacial defect called cyclopia (Binns et al., 1965 James, 1999 Figure 2.8). Tracheal stenosis, skeletal malformations and early embryonic death are also common (Keeler and... 

Oral exposure of pregnant rats to 750mg/kg/day for 10 gestational days induced slightly decreased fetal weight, delayed ossification of sternal and vertebral arches, and some early embryonic deaths. Maternal deaths also occurred at this dose, indicating that 2,4-DCP was not selectively toxic to embryos or fetuses. No effects were noted in dams or offspring exposed at 375 mg/kg/day. 

Parental injection of TMSN caused some fetal malformation and embryonic death but only at doses that caused severe maternal toxicity. ... 

Most cases are due to decreased expression of pymvate kinase activity, usually to 5-25% of normal levels complete loss of pyruvate kinase activity can cause embryonic death. 

Exposure by inhalation to methyl chloride causes fetal growth retardation and impaired male reproductive capacity in rats and malformations of the heart in fetal mice (lARC, 1986). The preimplantation losses described in rats in which the males were exposed to 6300 mg/m methyl chloride for 6 h per day for five days were due to a failure of fertilization rather than preimplantation embryonic death. A concentration of 2100 mg/m3 had no effect upon fertilization (Working Bus, 1986). 

Methyl chloride was mutagenic to bacteria and induced chromosomal aberrations in plants. It induced unscheduled DNA synthesis in cultured rat hepatocytes and, in rats exposed in vivo, there was a small increase in unscheduled DNA synthesis in hepatocytes but not in tracheal epithelial cells or spermatocytes. DNA strand breaks were induced by methyl chloride in the kidney cells of exposed mice. In cultured mammalian cells, it induced mutations and sister chromatid exchanges and enhanced viral cell transformation. It induced dominant lethal effects in rats. The last effect appears to be due to a failure of the males to fertilize the females, rather than to preimplantation embryonic death and can be partially inhibited by treatment with an anti-inflammatory agent (Chellman et al., 1986c). 

Bowes GW, Simoneit BR, Burlingame AL, et al. 1973. The search for chlorinated dibenzofurans and chlorinated dibenzodioxins in wildlife populations showing elevated levels of embryonic death. Environ Health Perspect 5 191-198. 

The effect of a mutation-induced impairment on human well-being is not necessarily the same as its effect on survival and fertility (Darwinian fitness). A mutant gene or altered chromosome may cause great pain or anguish without any great effect on survival and fertility. A mutation that causes early embryonic death is severe from the standpoint of Darwinian fitness, but with little social impact it is eliminated quickly from the population. Despite these exceptions and reservations, there is... 

This test146 deals primarily with gross chromosomal damage. The dominant-lethal test is widely used and is usually performed on exposed males. Nongenetic maternal effects make it much more difficult to study induction of dominant lethality in females. Exposed male rats or mice are mated at weekly (or shorter) intervals to cover the span of spermatogenesis of interest. Females usually are killed for uterine examination around day 14, and the numbers of total implantations and fetal or embryonic deaths are recorded. The corpora lutea are also counted sometimes. The proportions can be analyzed statistically to see whether dominant lethality has been induced, and appropriate formulas are used in calculating the percentage of dominant lethality.107 146... 

In one study, repeated doses of hCG between days 24 and 38 of pregnancy resulted in embryonic death but similar doses of hCG after day 39 did not result in pregnancy loss (Allen 1983). A single dose of PGF2a or its analogs between days 12 and 35 of pregnancy has been shown to cause embryonic death. After day 35, repeated injections of PGp2a are required to cause embryonic loss. 

The sulfonamides and pyrimethamine (e.g. for equine protozoal myeloencephalitis (EPM) can cause abortion in mares and abnormalities in newborn foals (see Chs 2 and 3) even when the mares received folic acid supplementation. Trimethoprim-sulfamethoxazole given to mares for up to 1 week prior to and after breeding does not appear to potentiate early embryonic death and has not been associated with an increase in birth defects in foals (J. Brendemuehl, personal communication, 2001). Birth defects have not been identified in foals born to mares undergoing... 

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