Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Αντσακλής Αριστείδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσατσάκης Αριστείδης, Καθηγητής, Ιατρική Σχολή, Πανεπιστήμιο Κρήτης
Γρηγοριάδης Θεμιστοκλής, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ, Επιβλέπων
Ντόμαλη Αικατερίνη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Θωμάκος Νικόλαος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δασκαλάκης Γεώργιος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τζατζαράκης Εμμανουήλ, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, Πανεπιστήμιο Κρήτης
Original Title:
Προσδιορισμός των επιπέδων ενδοκρινικών αναστολέων στο αμνιακό υγρό και συσχέτισης τους με τις συγκεντρώσεις τους στο αίμα εγκύων γυναικών. Μελέτη της επίδρασης τους στην εμβρυϊκή ανάπτυξη, την έκβαση της κύησης και τη νεογνική νοσηρότητα.
Translated title:
Determination of levels of endocrine inhibitors in amniotic fluid and their association with their concentrations in the blood of pregnant women. Study of their effect on fetal development, pregnancy outcome and neonatal morbidity.
Summary:
The aim of the present doctoral thesis is the estimation of neonatal exposure to endocrine disrupting chemicals which interfere with the synthesis, secretion and chemical bonding of the natural reproductive hormones or hormones that are responsible for the developmental processes.
The compounds with endocrine effects that were examined are the organochlorine insecticides DDTs (Dichlorodiphenyltrichloroethane), namely the isomers opDDE, ppDDE, opDDT, ppDDT, opDDD and ppDDD, the PCBs (Polychlorinated biphenyls), namely the isomers 28, 52, 101, 118, 153 and 180 and the HCB (Hexachlorobenzene). These chemicals are highly lipophilic, resistant to degradation and their long half-life in the human body and the environment has resulted in their accumulation in the food chain although they have been banned since decades.
The present thesis aims to measure and estimate the overall exposure and body burden of pregnant women to these chemicals, the prenatal exposure of their infants and to correlate the exposure with problems during pregnancy and infants’ health. For this purpose, hair samples, amniotic fluid and maternal blood were collected during the 16th and 21st week of pregnancy from 120 women. All participants were informed about the study and they answered questionnaires about health problems, problems during pregnancy, maternal somatometric characteristics and age as well as infants’ gender, health and developmental parameters.
New analytical protocols were developed for the sample treatment with high sensitivity for the detection of the pollutants at low concentrations and they were based on the automated solid phase extraction technique HS-SPME (Headspace-Solid Phase Micro-Extraction). The extraction parameters are a fiber PDMS/DVB 65 μm, temperature at 90o C, extraction time 30 min, agitation speed 250 rpm, autosampler AOC-5000. The instrumental analysis was performed with gas chromatography-mass spectrometry (GC-MS), SIM (selected ion monitoring) mode and three ions m/z were used for the quantification and qualification of the target compounds.
The instrumental response and the analytical method were linear and low LODs (limits of detection) were achieved at range 0.104-6.093 pg/mg for DDTs and HCB in hair samples, 0.008-0.268 ng/ml in serum and 0.001-0.011 ng/ml in amniotic fluid. The LODs for PCBs were 0.098-1.792 pg/mg in hair, 0.005-0.086 ng/ml in serum and <0.001-0.011 ng/ml in amniotic fluid.
The mean age of the study population was 37.7 years old and the majority of the participants were Greeks (85.8%). Most of the women were non-smokers (69.2%) and 37.1% of the smokers (13/35 women) continued smoking during pregnancy. 24.2% and 5.8% of the participants had thyroid problems and diabetes, respectively and there were also a few women that faced gastrointestinal diseases, blood pressure and cardiopulmonary diseases. For the most of the participants (53.3%) this was the first pregnancy and the women who gave caesarian birth were 30%.
The biomonitoring results for PCBs showed that the 101 isomer was the most frequently detected compound in all biological matrices and the rest were detected at frequency below 10%. For DDTs, the ppDDE was the main compound and it was detected at frequency 77.9% in hair, 94.9% in amniotic fluid and 85.5% in serum. The opDDE was detected at 4.8% in serum and 23.7 in hair and the ppDDT was not detected in any matrix. The detection frequency for HCB was 22.9% in serum, 18.3% in hair and 5.1% in amniotic fluid.
The mean?median? concentrations in hair samples were 8.2 pg/mg for DDEs, 28.6 pg/mg for DDDs and 36.5 pg/mg fοr the sumDDTs (DDEs, DDDs and DDTs). Serum samples were mostly burdened with PCBs (0.429 ng/ml), DDEs (0.092 ng/ml) and HCB (0.029 ng/ml). The compounds HCB and PCB101 isomer were detected at similar concentrations in amniotic fluid and hair samples. The concentrations of PCB101 in the pairs hair-amniotic fluid, hair-serum and serum-amniotic fluid were positively correlated. Participants who smoked during pregnancy were highly burdened with DDTs (55.9 pg/mg in hair) compared with non-smokers (28.4 pg/mg in hair), but this difference was not observed for the other compounds. Finally, differences were observed for the concentrations of PCB101 between women who gave preterm birth and full term pregnancy; participants with preterm birth had significantly higher levels of PCB101 in all biological matrices.
Main subject category:
Health Sciences
Keywords:
Levels of endocrine inhibitors, Amniotic fluid, Fetal development, Pregnancy outcome, Neonatal morbidity
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