Epigenetički i razvojni parametri u posteljicama ženki štakora izloženih alfa-cipermetrinu tijekom gestacije

master's thesis

• Title (english): Epigenetic and developmental parameters in placentas of rats exposed to alfa-cypermethrin during gestation
• Author: Petra Petrina
• Mentor: Anja Katić (mentor)
• Mentor: Inga Urlić (sumentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Mirjana Pavlica (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-04-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alfa-cipermetrin je piretroidni insekticid tipa II, široko korišten u poljoprivredi, kućanstvima i
veterini. Istraživanjima je dokazano djelovanje piretroida kao endokrinih disruptora. Zbog
zastupljenosti velikog broja hormonskih receptora, posteljica je posebno osjetljiva na učinke
ovakvih spojeva. Cilj ovog istraživanja bio je po prvi puta istražiti učinak α-cipermetrina na
globalnu metilaciju DNA, rast i apoptozu stanica te histopatološke promjene u posteljicama ženki
štakora izloženih α-cipermetrinu peroralno tijekom gestacije. U tu svrhu je metodom
pirosekvenciranja analiziran postotak metilacije tri CpG dinukleotida unutar ponavljajućih
sekvenci LINE-1, imunohistokemijskom metodom analizirana je ekspresija fosforiliranog histona
H3 kao proliferacijskog markera te pocijepane kaspaze-3 kao apoptotskog markera, te je
napravljena histopatološka analiza. S porastom doze α-cipermetrina ne dolazi do statistički
značajnog smanjenja globalne metilacije DNA. Pri testiranim koncentracijama α-cipermetrin ne
uzrokuje apoptozu, ali u koncentracijama od 10 i 19 mg/kg/dan dovodi do statistički značajnog
smanjenja proliferacije. Rezultati histopatološke analize pokazali su brojne promjene u tkivu
posteljice, koje također nisu bile statistički značajno različite u odnosu na kontrolne skupine.
Potrebno je provesti dodatna istraživanja u svrhu boljeg razumijevanja djelovanja α-cipermetrina
kao endokrinog disruptora na epigenetičke i razvojne parametre u posteljicama ženki štakora
izloženih tijekom gestacije.

Abstract (english)

Alpha-cypermethrin is a type II pyrethroid pesticide, widely used in agriculture, households and
veterinary medicine. Research has shown that pyrethroids act as endocrine disruptors. Due to the
abundance of hormone receptors, the placenta is highly sensitive to these compounds. The aim of
this research was to investigate for the first time the effects of α-cypermethrin on global DNA
methylation, growth, apoptosis and histopathological changes in placentas of female rats exposed
orally during gestation. For this purpose, the methylation level of three CpG dinucleotides within
LINE-1 repeats was analyzed by pyrosequencing, protein expression of phosphorylated histone H3
as a marker of proliferation and cleaved caspase-3 as a marker of apoptosis were detected by
immunohistochemistry and a histopathological analysis was performed. The increase of αcypermethrin dosage isn’t followed by a statistically significant decrease in global DNA
methylation. Alpha-cypermethrin doesn’t induce apoptosis at tested concentrations, but at
concentrations of 10 and 19 mg/kg/day significantly decreases cell proliferation. Many
histopathological changes were detected in placentas, but their occurrence wasn’t statistically
significant in comparison with control groups. Further research is needed to better understand the
effects of α-cypermethrin as an endocrine disruptor on epigenetic and developmental parameters
in placentas of female rats exposed during gestation.

• Keywords: endokrina disrupcija; histopatologija; imunohistokemija; piretroid; pirosekvenciranje; skotne ženke štakora
• Keywords (english): endocrine disruption; histopathology; immunohistochemistry; pyrethroid; pyrosequencing; pregnant female rats
• Language: croatian
• URN:NBN: urn:nbn:hr:217:436468
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-04-28 07:40:20