Krysiak-Baltyn, Konrad

I løbet af de seneste fire årtier er forekomsten af testikelkræft og andre mandlige reproduktionsforstyrrelser steget kraftigt. Denne stigning ses overvejende i udviklede og industrialiserede lande og betragtes for stor til at kunne forklares af genetiske faktorer alene. Miljømæssige faktorer er derfor mistænkt for at spille en vigtig rolle for denne trend, og klinisk forskning forsøger ihærdigt at identificere virkningsmekanismerne bag. Disse er endnu ukendt, men en række genetiske faktorer og miljømæssige kemikalier er identificeret til at være risikofaktorer for mandlige reproduktionsforstyrrelser - de fleste fundet ved dyreforsøg.En general hypotese for årsagen til en række mandlige reproduktionsforstyrrelse kaldes testikulært dysgenese syndrom (TDS), hvor forstyrrelserne finder sted allerede under fosterudviklingen. Forstyrrelserne har en dybtgående indvirkning, og konsekvenserne forplanter sig ind i voksenlivet I form af dårlig sædkvalitet, kryptorkisme og testikelkræft.Arbejdet i denne ph.d.-afhandling har primært fokuseret på de miljømæssige aspekter af TDS. Det er forsøgt yderligere at underbygge hypotesen om, at miljøfaktorer kan spille en afgørende rolle i den øgede hyppighed af mandlige reproduktionsforstyrrelser.Denne afhandling er inddelt i fire dele. I den første del giver jeg en introduktion til mandlige reproduktionsforstyrrelser og den aktuelle situation på området. I den anden del fokuserer jeg på undersøgelser af kemikalier i miljøet og deres mulige indvirkning på reproduktiv sundhed. I tredje del diskuterer jeg netværksbiologi som et stærkt værktøj til undersøgelse af gen-gen og kemikalie-gen interaktioner. I den fjerde del diskuterer jeg "association mining" af kliniske data som et middel til at finde interessante og uventede sammenhænge mellem livsstilsfaktorer og sygdom.During the past four decades, the incidence rates of testicular cancer and other male reproductive disorders have been increasing at a rapid rate, predominantly in developed and industrialized countries. This increase is considered too great to be explained by genetic factors alone, and thus environmental factors have strongly been suspected to play a major role. There is a large amount of clinical research which has tried to pinpoint the mechanism of action for this trend.Although the exact mechanism of action has not been elucidated, a number of genetic factors as well as environmental chemicals have been found, mostly in animal studies, to act as risk factors for the disorders. The common consensus today is that there exists a common causal mechanism for a number of different male reproductive disorders which takes place before birth, during fetal development, and is termed Testicular Dysgenesis Syndrome (TDS). TDS occurs when certain critical developmental events are disturbed, and has a profound effect that propagates into adulthood, which may lead to lower sperm concentration, cryptorchidism and testicular cancer.The work within this PhD thesis has primarily focused on the environmental aspects of TDS, generating further support for the hypothesis that environmental factors may play a critical role in the observed trends.This thesis is divided into four parts. In the first part I introduce male reproductive disorders and the current state of affairs. In the second part, I focus on studies of environmental chemicals and their possible impact on reproductive health. In the third part, I discuss network biology as a powerful tool for the study of gene-gene and chemical-gene interactions. In the fourth part, I discuss association mining of clinical data as a means to find interesting and unexpected associations between life style factors and disease. The thesis ends with concluding remarks

Online Research Database In Technology

Environmental and Life Style Factors in Relation to Male Reproductive Disorders

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Environmental and Life Style Factors in Relation to Male Reproductive Disorders

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