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The impact of organophosphorus pesticides on the occurrence of the undescended testis

dc.contributor.advisorŽivković, Dragana
dc.contributor.advisorVejnović, Tihomir
dc.contributor.otherVarga, Jan
dc.contributor.otherŽivković, Dragana
dc.contributor.otherGajdobranski, Đorđe
dc.contributor.otherBukarica, Svetlana
dc.contributor.otherGudurić, Branimir
dc.creatorFratrić, Ivana
dc.date.accessioned2019-12-23T16:36:35Z
dc.date.available2019-12-23T16:36:35Z
dc.date.available2020-07-03T13:24:38Z
dc.date.issued2019-10-31
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija155921709905864.pdf?controlNumber=(BISIS)110721&fileName=155921709905864.pdf&id=12929&source=NaRDuS&language=srsr
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/11569
dc.identifier.urihttps://www.cris.uns.ac.rs/record.jsf?recordId=110721&source=NaRDuS&language=srsr
dc.identifier.urihttps://www.cris.uns.ac.rs/DownloadFileServlet/IzvestajKomisije155921711168454.pdf?controlNumber=(BISIS)110721&fileName=155921711168454.pdf&id=12930&source=NaRDuS&language=srsr
dc.identifier.urinull/DownloadFileServlet/IzvestajKomisije155921711168454.pdf?controlNumber=(BISIS)110721&fileName=155921711168454.pdf&id=12930
dc.description.abstractNespušteni testis predstavlja odsustvo testisa u skrotumu sa jedne ili obe strane. Faktori rizika za pojavu nespuštenog testisa obuhvataju genetsku predispoziciju, prevremeno rođenje, nisku porođajnu masu i prenatalnu izloženost endokrinim disruptorima ili duvanskom dimu. Endokrini disruptori se definišu kao egzogene supstance koje imaju uticaj na homeostazu organizma i proizvodnju reproduktivnih hormona. U ovoj grupi nalaze se organofosforni pesticidi koji se široko upotrebljavaju u poljoprivredi. Većina organofosfornih pesticida ima antiandrogeni uticaj i uz činjenicu da živimo u pretežno agrarnoj sredini predmet su našeg interesovanja. Cilj istraživanja je da se utvrdi razlika u izloženosti organofosfornim pesticidima korišćenjem upitnika kreiranog po modelu standardizovanog Evropskog upitnika QLK 4-1999-01422 kod osoba koje su rodile zdravu mušku decu i osoba koje su rodile decu sa nespuštenim testisom. Pored toga, cilj istraživanja je i da se odredi i uporedi vrednost metabolita organofosfornih pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat i dietilditiofosfat) u urinu majki koje su rodile mušku decu sa nespuštenim testisima i majki koje su rodile zdravu mušku decu. Metodologija: Rad je radomizovano, prospektivno, kliničko istraživanje sprovedeno na Klinici za ginekologiju i akušerstvo Kliničkog centra Vojvodine i Katedri za farmakologiju i toksikologiju Medicinskog fakulteta, Univerziteta u Novom Sadu. U kliničko istraživanje uključeno je 50 porodilja koje su rodile mušku decu sa nespuštenim testisima (eksperimentalna grupa) i 53 porodilje koje su rodile zdravu mušku decu (kontrolna grupa) u periodu od oktobra 2012. godine do aprila 2018. godine. Tokom boravka u porodilištu ispitanice su popunjavale upitnik o navikama nakon čega im je uzet uzorak urina radi analiziranja nivoa metabolita OF pesticida. Uzorci urina su pripremljeni metodom koju su opisali Wu i saradnici 2010. godine, a potom analizirani na gasnom hromatografu masenom spektrofotometaru marke Agilent 7890A. Rezultati: Ispitivane grupe se ne razlikuju po starosti ispitanica (prosečna starost kontrolne grupe 29,41 ± 5,58 godina, a eksperimentalne 30,54 ± 4,87 godina). U obe grupe prosečno je ispitanicama ovo bila druga trudnoća. Ispitanice se nisu razlikovale ni po načinu porođaja. Prosečna gestacijska nedelja trudnoće na porođaju iznosila je 39,45 ± 1,38 nedelja za kontrolnu grupu i 39,20 ± 1,38 nedelja za eksperimentalnu grupu, a porođajna masa novorođenčeta 3527,30 ± 470,16 g u kontrolnoj grupi i 3404,37 ± 508,20 g u eksperimentalnoj grupi. Statistički značajna razlika postoji u odnosu na mesto stanovanja (50,9 % ispitanica kontrolne grupe i 77,6 % ispitanica eksperimentalne grupe žive u gradu), jedinicu stanovanja (67,9 % kontrolne i 45,7 % ispitanica eksperimentalne grupe žive u kući) i načinu začeća (6 % ispitanica eksperimentalne i 1,9 % ispitanica kontrolne grupe prijavilo je IVF kao način začeća). Skoro polovina ispitanica obe grupe su pušači, a njih 32,7 % kontrolne grupe i 38,8 % eksperimentalne pušile su i tokom trudnoće. Izloženost pesticidima prijavilo je 50,9 % ispitanica kontrolne i 44 % ispitanica eksperimentalne grupe, a profesionalnu izloženost prijavilo je 3 ispitanice kontrolne i 2 ispitanice eksperimentalne grupe. Ispitanice se ne razlikuju ni po poreklu voća i povrća koje konzumiraju, kao ni po vrsti voća koje su konzumirale tokom trudnoće. Prosečne izmerene vrednosti DMF u kontrolnoj grupi iznose 5,604 ± 6,103 ug/L, a u eksperimentalnoj 4,815 ± 6,729 ug/L. Izmerene vrednosti DEF u kontrolnoj grupi su 0,408 ± 0,447 ug/L, a u eksperimentalnoj 0,461 ± 0,593 ug/L. Nivo DMDTF u kontrolnoj grupi bio je 0,431 ± 0,508 ug/L, a u eksperimentalnoj 0,547 ± 0570 ug/L, a DETF 0,403 ± 0,606 ug/L u kontrolnoj i 0,529 ± 0,725 ug/L u eksperimentalnoj grupi. Ni jedan metabolit ne pokazuje statistički značajnu razliku u ispitivanim grupama. Slične vrednosti dobijene su i za vrednosti korigovane za nivo kreatinina. Univarijantna regresiona analiza pokazala je da ispitanice koje žive u gradu imaju 3,3 puta veće šanse da rode dete sa nespuštenim testisom, a one koje žive u stanu imaju 2,5 puta veće šanse za isti ishod. Statistički značajna razlika primećena je u nivou DEDTF u zavisnosti od starosti ispitanica i jedinici stanovanja. Više vrednosti DETF dobijene su kod ispitanica koje su bile na hormonskoj terapiji tokom trudnoće. Ispitanice koje su prijavile da su bile izložene pesticidima tokom trudnoće u urinu su imale statistički značajno više vrednosti DMDTF u odnosu na ispitanice koje su se izjasnile da nisu bile izložene pesticidima. Slični rezultati za vrednost DEDTF dobijeni su kod ispitanica koje su se izjasnile da poseduju kućne ljubimce. Statistički više vrednosti DEF i DETF korigovano za nivo kreatinina dobijene su kod ispitanica koje nisu konzumirale jabuke, a više vrednosti DEF i DEDTF dobijene su kod ispitanica koje su konzumirale maline i kupine tokom trudnoće. Ostale grupe nisu pokazale statistički značajnu razliku među ispitivanim grupama. Zaključci: Izloženosti trudnica OF pesticidima nije značajno veća u grupi majki koje su rodile decu sa nespuštenim testisom u odnosu na izloženost OF pesticidima kod majki zdrave muške dece. Vrednosti metabolita OF pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat, dietilditiofosfat) u urinu majki koje su rodile mušku decu sa nespuštenim testisima nije viša u odnosu na vrednosti metabolita OF pesticida (dimetilfosfat, dimetilditiofosfat, dietilfosfat, dietiltiofosfat, dietilditiofosfat) izmerene u jutarnjem urinu majki koje su rodile zdravu mušku decu.sr
dc.description.abstractUndescended testis is the absence of testis in the scrotum on one or both sides. Risk factors for the occurrence of undescended testis include genetic predisposition, premature birth, low birth weight and prenatal exposure to endocrine disruptors or tobacco smoke. Endocrine disruptors are defined as exogenous substances that can affect homeostasis of the organism and the production of reproductive hormones. In this group are organophosphorus pesticides that are widely used in agriculture. Most of organophosphorus pesticides have anti-androgenic effect and with the fact that we live in a predominantly agricultural area, they are the focus of our interest. The aim of the research: The aim of this study is to determine the difference in exposure to organophosphorous pesticides using questionnaires created by standardized European model questionnaire QLK 4-1999-01422 in individuals who gave birth to a healthy male children and women who gave birth to children with undescended testis. In addition, the aim of this study is to determine and compare the value of metabolites of organophosphorus pesticides (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) in the urine of mothers who gave birth to male children with undescended testis and mothers who gave birth to healthy male children. Methodology: This work is randomized, prospective, clinical research conducted at the Clinic for gynaecology and obstetrics of the Clinical center of Vojvodina and the Department of Pharmacology and toxicology of the Faculty of Medicine, University of Novi Sad. This clinical research includes 50 new mothers that gave birth to male children with undescended testes (experimental group) and 53 new mothers that gave birth to healthy male children (control group) in the period from October 2012 to April 2018. During their stay at the maternity hospital the subjects were asked to fill out a questionnaire about habits and to give a urine sample for analyzing the level of metabolites of organophosphus pesticides. Urine samples were then prepared using the method described by Wu and associates 2010, and analyzed on gas chromatograph with a mass spectrophotometer Agilent 7890A brand. Results: Study groups do not differ according to the age of women (average age of control group is 29.41 ± 5.58 years, and experimental 30.54 ± 4.87 years). In both groups this was second pregnancy on average. The subjects did not distinguish either by the way of delivery. The average gestational weeks of pregnancy to childbirth was 39.45 ± 1.38 weeks for the control group and 39.20 ± 1.38 weeks for the experimental group, and birth weight of newborn was 3527.30 ± 470.16 g in control group and 3404.37 ± 508.20 g in the experimental group. There is no statistically significant difference in relation to the place of residence (50.9 % of the control group and 77.6 % of experimental live in the city), the living unit (67.9 % and 45.7 % of the control and experimental groups are living in the house) and the way of conception (6 % of experimental and 1.9 % of the control group reported IVF as a way of conception). Nearly half of both groups are smokers, and 32.7 % of women in the control group and 38.8 % in experimental smoked during pregnancy. Exposure to pesticides reported 50.9 % of mothers in control and 44 % of mothers in the experimental group. Professional exposure was reported by 3 control subjects and 2 subjects in experimental group. The subjects did not differ according to the origin of fruits and vegetables they were consuming, neither regarding the type of fruits they consumed during pregnancy. Average level of dimethylphosphate in control group was 5.604 ± 6.103 ug/L, and in experimental 4.815 ± 6.729 ug/l. Levels of diethylphosphate in control group were 0.408 ± 0.447 ug/L, and in experimental 0.461 ± 0.593 ug/l. DMDTP level in the control group was 0.431 ± 0.508 ug/L, and in experimental 0.547 ± 0570 ug/L, and the DETP was measured 0.403 ± 0.606 ug/L in control, and 0.725 ± 0.529 ug/L in the experimental group. These metabolites showed no statistically significant difference in the examined groups. Similar values are obtained for the adjusted values for creatinine level. Univariate regression analysis showed that the subjects who live in town are 3.3 times more likely to have child with undescended testis, and those who live in the apartment are 2.5 times more likely for the same outcome. Statistically significant difference was noticed in DEDTP level depending on the age of the subject and the living unit. Higher levels of DETP metabolites were detected in subjects that have been on hormonal therapy during pregnancy. The subjects who reported being exposed to pesticides during pregnancy had statistically significantly higher DMDTP values in relation to the subjects that were not exposed to pesticides. Similar results are obtained for the DEDTP level with higher levels in subjects owning pets. Statistically higher levels of DEP and DETP adjusted for creatinine were obtained in subjects that were not reporting eating apples, and higher levels of DEP and DEDTP were obtained in subjects that consumed raspberries and blackberries during pregnancy. Other groups showed no statistically significant difference between the study groups. Conclusion: Exposure of pregnant women to OP pesticides is not significantly greater in the group of mothers who gave birth to children with undescended testis in relation to exposure to OP pesticides in mothers of healthy male children. The level of OP metabolites (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) in the urine of mothers who gave birth to children with undescended testis is not higher in relation to the levels of OP metabolites (dimethylphosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate and diethyldithiophosphate) recorded in urine of mothers who gave birth to healthy male children.en
dc.languagesr (latin script)
dc.publisherУниверзитет у Новом Саду, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41012/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Новом Садуsr
dc.subjectkriptorhizamsr
dc.subjectCryptorchidismen
dc.subjectPesticidesen
dc.subjectPhosphoric Acidsen
dc.subjectEndocrine Disruptorsen
dc.subjectRisk Factorsen
dc.subjectTestisen
dc.subjectMaternal Exposureen
dc.subjectpesticidisr
dc.subjectfosforna kiselinasr
dc.subjectendokrini disruptorisr
dc.subjectfaktori rizikasr
dc.subjecttestissr
dc.subjectizloženost majkesr
dc.titleUticaj organofosfornih pesticida na pojavu nespuštenog testisasr
dc.title.alternativeThe impact of organophosphorus pesticides on the occurrence of the undescended testisen
dc.typedoctoralThesissr
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34104/IzvestajKomisije.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/34103/Disertacija.pdf


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