Intergenerational thyroid hormone homeostasis imbalance in cerebellum of rats perinatally exposed to glyphosate-based herbicide.

Agrochemicals became a public health concern due to increased human exposure and possible endocrine disruption effects in several organs, including the brain. Thyroid hormones controls neurodevelopment, which turn them sensitive to endocrine disruptors (EDs). In this work, we evaluated the effect of glyphosate-based herbicides (GBH) as an intergenerational endocrine disrupter on thyroid homeostasis in cerebellar cells. Female pregnant Wistar rats were exposed to Roundup Transorb® solution at 5 and 50 mg/kg/day, from gestation day 18 to post-natal day 5 (P5). Cerebellum of male offspring was used to evaluate gene expression. The mRNA levels of thyroid hormone receptors, hormonal conversion enzymes, hormone transporters, as well as, de novo epigenetic regulators were altered, with some of these genes presenting a non-monotonic dose response. Furthermore, metabolomic profile correlation with tested dose demonstrated altered metabolic profile, in agreement with cerebellar gene alterations. Moreover, cerebellar primary cultures exposed to non-toxic GBH concentration presented a decrease level in glial fibrillary acidic protein, a protein regulated by endocrine signals. In conclusion, our results indicate that animals exposed to non-toxic GBH doses during perinatal phase carry intergenerational alterations in key regulators of cellular thyroid hormone homeostasis and epigenetic controllers in adulthood, indicating the possible ED effect of GBH based on epigenetic alterations.

Dental caries: Genetic and protein interactions.

OBJECTIVE: To present a genetic and protein interaction analysis associated with dental caries. MATERIAL AND METHODS: The first step was to conduct a systematic literature review (SLR) through an electronic database search. Case-controls that reported associations between genes and dental caries were the main type of study design used as inclusion criteria, retrieved from the PubMed and the Virtual Health Library databases, comprising the chronological range from 1982 to 2017. The SLR was guided by PRISMA protocol and the methodological quality of the studies was established through Newcastle-Ottawa Scale (NOS). In the second step, the String Protein Interaction (SPI) approach was used to analyze protein interaction (by esyN software) and also the Ingenuity Pathway Analysis (IPA) to check biological pathways associated with dental caries genes. RESULTS: A total of 51 articles were included to perform this SLR, describing a number of 27 genes associated with dental caries development. At the genetic level, 23 genes have at least one other gene with which they interact. The genes TUFT1, VDR, TFIP11, LTF, HLA-DRB1, MMP2, MMP3 and MUC5B were shown to be connected in interactive networks by at least 10 other genes. CONCLUSION: It is essential to apprehend the multifactorial pattern of inheritance in human disease. This study presents pathways which may be directly correlated with several dental caries phenotype and this contributes to a better understanding of this disease, opening up a wider range of biotechnology options for its effective control in the future.