Učinak kadmija na funkcije posteljice u prijenosu esencijalnih mikroelemenata i sintezi steroidnih hormona u štakorica

doctoral thesis

• Title (english): The effect of cadmium on placental functions in transport of essential microelements and steroid hormone synthesis in rats
• Author: Anja Mikolić; MBZ: 296736
• Mentor: Martina Piasek (mentor); MBZ: 113132
• Committee member: Valerije Vrček (član povjerenstva)
• Committee member: Irena Žuntar (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva); MBZ: 221301
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2016-03-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Hrana je glavni izvor izloženosti ljudi esencijalnim i toksičnim metalima, uključujući kadmij (Cd). Cilj istraživanja je bio procijeniti učinke peroralne izloženosti Cd tijekom skotnosti štakorice na razdiobu kadmija i stanje mikronutrijenata u majčinom organizmu i fetusu te funkcije posteljice u prijenosu nutrijenata i sintezi steroidnih hormona. Hipoteze istraživanja su bile da se tijekom graviditeta povećava želučanocrijevna apsorpcija Cd koji se nakuplja u posteljici i može poremetiti prijenos nutrijenata do fetusa i sintezu posteljičnih hormona. Pokusne štakorice (Wistar) su nakon parenja izlagane dozi od 50 mg Cd/l (u obliku CdCl2xH2O) u vodi za piće od 1. do 19. ili 20. dana skotnosti. Neskotne štakorice su istodobno izlagane pod jednakim uvjetima izloženosti tijekom 20 dana. Posljednjeg dana pokusa je svim štakoricama u općoj anesteziji izvađena krv iz srca i uzorkovani unutrašnji organi, posteljice i fetusi, koji su pripremljeni za analize mikroelemenata (metodom AAS). Progesteron i testosteron su analizirani imunokemijski izravno u serumu (metodom IEMA) i u uzorcima pripremljenim iz posteljičnog tkiva (metodama IEMA i/ili ELISA). U svih izloženih štakorica su nađena povećanja Cd u svim izmjerenim uzorcima i cinka u jetri. Količine željeza u fetusu i cinka u fetusu i/ili posteljici su bile smanjene. U izloženih skotnih vs. izložene neskotne štakorice su bila izraženija povećanja koncentracije Cd u krvi i količina Cd u jetri i bubregu kao i smanjenja količina željeza u jetri i bubregu te cinka i bakra u bubregu. U svih skotnih vs. neskotne štakorice su bile veće koncentracije Cd u krvi i količine bakra u bubregu te manje količine željeza u jetri i bubregu i bakra u jetri. Nije bilo promjena u steroidnim hormonima ni u serumu, ni u posteljici, u kojoj su vrijednosti svakog hormona izmjerene dvjema imunokemijskim metodama značajno korelirale. U zaključku, ovim radom su dobiveni izvorni podaci o vrijednostima progesterona i testosterona (kao prekusora za sintezu estradiola u jajniku) u serumu i posteljici štakorice blizu roka okoćenja. Novi i izvorni znanstveni rezultati su da peroralna izloženost štakorica dozi od 6,5 mg Cd/kg tjelesne mase otopinom za napajanje tijekom skotnosti povećava razine Cd u krvi, jetri i bubregu s posljedičnim biokemijskim promjenama mikronutrijenata u većoj mjeri nego u neskotnih štakorica što istodobno s nakupljanjem Cd u posteljici remeti transplacentarni prijenos željeza i cinka te može predstavljati opasnost za rast i razvoj fetusa in utero.

Abstract (english)

Food is the main source of human exposure to essential and toxic metals, including cadmium (Cd). This investigation aimed to assess the effects of oral Cd exposure during rat pregnancy on Cd distribution and micronutrient status in a maternal organism and foetus and placental functions in nutrient transport and steroid hormone synthesis. Research hypotheses were that Cd gastrointestinal absorption increases during pregnancy and Cd accumulates in the placenta where it may interfere with nutrient transport to the foetus and placental hormone biosynthesis. Female rats (Wistar) were mated and exposed to 50 mg Cd/l (as CdCl2xH2O) in drinking water from gestation day 1 through 19 or 20. Non-pregnant rats were concurrently exposed during 20 days under the same exposure conditions. On the last experimental day, under general anaesthesia, blood was taken by cardiac puncture from all of the rats and internal organs, placentas and foetuses were dissected and prepared for element analysis (by AAS). Progesterone and testosterone were assayed by immunochemical methods directly in sera (by IEMA) and in placental tissue-derived samples (by IEMA and/or ELISA). All of the exposed rats exhibited increases in Cd in all of the analysed samples and zinc in the liver. Contents of iron in the foetus and zinc in the foetus and/or placenta were decreased. In exposed pregnant vs. exposed non-pregnant rats, more pronounced increases in Cd concentration in the blood and Cd contents in the liver and kidney, decreases in iron contents in the liver and kidney, and decreases in zinc and copper contents in the kidney were recorded. In all pregnant vs. non-pregnant rats, higher Cd concentrations in the blood and copper content in the kidney and lower iron contents in the liver and kidney and copper content in the liver were found. Steroid hormones did not change in either the serum or placenta; in the latter the values of either hormone measured by two immunochemical assays were correlated. In conclusion, this work provides original evidence on progesterone and testosterone (as the precursor for the ovarian oestradiol synthesis) in rat serum and placenta at term. New and original research results are that oral Cd exposure to 6.5 mg Cd/kg body mass in drink during rat pregnancy increases levels of Cd in the blood, liver and kidney with consequent biochemical changes of micronutrients more pronouncedly than in non-pregnant rats, which together with accumulation of Cd in the placenta disrupts the transplacental handover of iron and zinc and may put at risk foetal growth and development in utero.

• Keywords: kadmij; posteljica; fetus; željezo; cink; bakar; progesteron; testosteron; graviditet
• Keywords (english): cadmium; placenta; foetus; iron; zinc; copper; progesterone; testosterone; pregnancy
• Language: croatian
• URN:NBN: urn:nbn:hr:163:473049
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-04-07 13:19:00