RESUMO
The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44⯵g/kg; 15.07⯵g/kg and 189,42⯵g/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine.
RESUMO
Polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals (EDCs). Their presence in the environment is particularly concerning in cases of fetal exposure, which is the most vulnerable period of life for both human and animals who share the same environment. Placenta, as a sample collected using noninvasive methods to screen EDCs, is a good indicator for potential fetal exposure. Although recent studies indicate that companion animal may correspond to human exposure, species-specific anatomo-morphological and metabolic differences are controversial. In this study, placenta samples of 60 women and 25 dogs living and giving birth within the same region were evaluated for the presence of PCB, OCP, PBDE, and PAH residues; where, socio-demographic factors were also assessed to identify the possible sources. Gas chromatography-mass spectrometry method was validated for the matrix, and among 45 screened and targeted pollutants, only 18 were found in human placentas. While the most frequently detected pollutants were DDTs, followed by PAHs and PCBs in decreasing order, the pollutants with the highest concentrations were PAHs, followed by PCBs and DDTs. Only five of the target contaminants were detected in the dog placentas. These results indicate that; as dogs have different bioaccumulation capacities and higher excretion rates than humans, the life-long effects of exposure to endocrine compound and possible consequences related to adverse health outcomes are expected to vary and concentrations cannot be directly correlated.
