Maternal effect

The 500-mg/kg/day dose also caused a significant decrease in maternal body weights. No effect on the number of fetuses with anomalies was observed, and no fetal or maternal effects were observed at lower doses. These studies suggest that in the absence of maternal effects, developmental effects in humans are unlikely. 

To demonstrate that a developmental effect is secondary to a particular parameter of maternal toxicity, it is necessary but not sufficient to show that all mothers with developmental toxicity also had maternal toxicity and that the severity of the developmental effect was correlated with the maternal effect. An example of such a correlation is shown in Figure 8.8, in which a drug-induced effect on maternal... 

However, the presence of concurrent maternal toxicity does not automatically mean that effects in the offspring have no significance. Mother and fetus could very well be equally sensitive to the toxicity of the substance, and effects in the offspring should not be considered to be secondary to maternal effects unless there is justification for this assumption. 

Administered to pregnant rats by inhalation 7 hours/day on days 1-19 of gestation, 8000 ppm caused reduced fetal weights, an increased incidence of skeletal malformations, and significant maternal toxicity in the form of narcosis and reduced feed consumption." At 3 500 ppm for the same exposure time, there were no fetal or maternal effects. 

Suh et al. (1983) administered chlorine dioxide in the drinking water of female rats for 2.5 months prior to mating with unexposed males, and during gestation days 1-20 at levels that resulted in estimated doses of 0.13, 1.3, or 13 mg/kg/day. The only reported maternal effect was a slight (but not significantly) decreased... 

One way to circumvent such (unjustified) labeling is to try to prove a causal relationship between the maternal effects and those in offspring, thus trying to show that the latter ones are unspecific secondary consequences of the former ones. So for the sound interpretation of study results it is important to find a good balance between maternal and fetal effects. For example, if a 10% reduction in maternal net weight gain is accompanied by a comparable reduction in fetal weight, then this puts the fetal effects in the correct perspective and would not lead the experimenter to conclude that the compound is a (specific) developmental toxicant. On the other hand if in the same situation the number of fetal anomalies (in particular malformations) is increased, then this could most unlikely be explained as a consequence of maternal toxicity. 

Unlike the situation for pharmaceuticals, where many maternal effects are expected from the nature of the substance, very few maternal effects in chemical studies are not adverse as previously mentioned, the test substance color and salivation due to unpleasant taste are probably the only exceptions to the rule. 

Effects on Fetuses That Are Secondary to Maternal Effects... 

OctaBDE commercial mixtures caused skeletal ossification variations in rats and rabbits at maternally toxic levels and other indications of fetotoxicity at lower doses (Argus Research Laboratories 1985b Life Science Research Israel Ltd. 1987). No maternal effects were observed in rats that were administered 2.5, 10, or 25 mg/kg/day doses of octaBDE (FR-1208) by gavage on Gds 6-15 (Life Science Research Israel Ltd. 1987). Fetal death, as measured by post-implantation loss, was somewhat elevated among litters from... 

C. Niisslein-Volhard, Maternal effect mutations that alter the spatial coordinates for the embryo of Drosophila melanogaster. In Determinants of Spatial Organization. S. Subtelny and 1. Konigsberg, eds.. Academic Press, New York, 1979, pp. 185-211. 

Maternal-Effect Gene Products for Oocytes Are Frequently Made in Helper Cells Gap Genes Are the First Segmentation Genes to Become Active... 

Based only on the definition of maternal-effect genes, segmentation genes, and homeotic genes, which do you predict act earliest in development of the Drosophila embryo, and which act latest ... 

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