Discussion
lethargy, LGA, hyperlordosis, convulsions, diarrhea, scoliosis, toxicity, Hydronephrosis, tremors, hydrocephalus, ataxia, reduced ossification or absence of ossification, weight gain, chromosomal damage, skeletal malformations, Hydrocephalus, Regarding skeletal malformations, visceral malformations
HYDRONEPHROSIS, SCOLIOSIS, HYDRONEPHROSIS, HYDROCEPHALUS, HYDROCEPHALUS, MALNUTRITION, EXCESSIVE SALIVATION
According to the literature, no data on maternal toxicity, reproductive performance, and embryofetal development were found for Our results show no signs of maternotoxicity, such as diarrhea, tremors, excessive salivation, convulsions, hypoactivity, ataxia, lethargy, tail curvature and hair raising [The animals started the experiments with similar weights; even EES1 at a dose of 100 mg/kg had the highest average. However, during gestation, this group showed the lowest weight gain. This fact was not only attributed to the lower number of fetuses since the difference in fetus frequency between the two EES1 treated groups was only one fetus. Additionally, the average fetal weight of EES1 at a dose of 100 mg/kg was the lowest of all the groups. Thus, these two facts may contribute to understanding weight gain reduction.Therefore, it is assumed that these animals had a lower biometric development (lower maternal weight gain) without the influence of the treatment, i.e., without maternotoxicity. In this context, the weight of the organs (of the liver) may vary according to the animal's size (large animals have heavier livers than small animals). This inference can be corroborated by the absence of a significant difference in the relative weight of this same organ. The relative weight corrects distortions of this type since it normalizes the data by making a ratio between the organ's weight and the animal's final weight. Thus, as there are no significant differences in the relative weight, it is inferred that such data is an isolated occurrence and is not due to the treatment. It is also noteworthy that, in general, xenobiotics that cause damage to the body lead mainly to an increase in the liver and kidneys and not their decrease [The absence of maternotoxicity is the absence of genotoxic effects evaluated by the micronucleus test. Regulatory agencies internationally accept this test for chromosomal damage assessment [This safety of use is corroborated by the studies of Radai et al. [Evaluation of parameters related to reproductive performance indicated that there were no differences (According to David et al. [Thus, it is considered that even in the face of reorganization of the organism to increase placental efficiency, the compensation of the EES1 (100 mg/kg) was insufficient to guarantee the same embryofetal growth in the mean fetal weight observed in the other experimental groups. However, when weight adequacy for gestational age was performed, it was observed that there were no significant differences between the fetuses of the treatment of EESl at a dose of 100 mg/kg and the control group, i.e., the occurrence of SGA, LGA, and AGA fetuses did not differ between these groups. But, when evaluating a higher dose at 1000 mg/kg group, an increase in the frequency of SGA was observed in the control group even though there was no change in placental weight, placental index, and placental efficiency.Reduced placental weight can be associated with fetal malnutrition, reduced growth, low weight gain, and lower placental index. The outcome of these changes can be reduced fetal weight [Assessments of placental function and the effects of gestational insults often use the ratio of birth weight to placental weight as a measure of placental efficiency [Regarding the occurrence of malformations, it was observed that EESl, at doses of 100 and 1,000 mg/kg, increased the frequency of external and skeletal malformations. However, visceral malformations increased only for the EESl (100 mg/kg) group. Among the external malformations, the ones that occurred the most were curved tail, hyperlordosis, and scoliosis, which are spinal alterations.Giampietro et al. [Li et al. [The primary visceral malformations identified were hydrocephalus and hydronephrosis. Hydrocephalus did not present significant differences between the groups. Therefore, they are considered variants of normality. Hydronephrosis increased significantly in the EESl (100 mg/kg) group. However, these changes may regress at birth since the fetuses were collected on gestational day 18, and the end of natural gestation would only occur on gestational day 21. Thus, these alterations could be correctable. However, this data requires attention.Some studies in the field [Regarding skeletal malformations, it was observed that EESl increased the frequency of reduced ossification or absence of ossification, especially in the skull and sternum. This change may occur due to the early removal of the fetus (18Evaluation of skeletal development is routinely performed in embryofetal development studies to support the development of new therapeutic agents because ossification patterns in humans and rodents are similar, with bones originating from intramembranous or endochondral ossification and processes controlled by genetic and environmental factors [