SEX DIFFERENCES IN LIVER GENE EXPRESSION IN WT AND SF-1 KNOCKOUT MICE
Authors: Kozinc Klenovšek Katja , Španić Tanja , Majdič Gregor 
Published: July 2018

Liver development and function are dependent on specific gene expression profile. Many genes in the liver are differentially expressed between females and males and these sex differences are thought to be at least partially influenced by sex specific patterns of growth hormone secretion. The aim of this study was to examine whether sex chromosomes contribute to sex differences in the liver gene expression. Expression of Cyp4a10, Cyp2u1, Cux2 and Hsd3b5, which are known to be differentially expressed between sexes in adulthood, were studied in WT and SF-1 knockout mice. Steroidogenic factor 1 knockout (SF-1 KO) mice that are born without gonads were used to determine whether there are any sex differences in the gene expression even in the absence of exposure to sex steroid hormones. Gonadectomised mice were also compared to gonadally intact mice and gene expression of studied genes was examined during estrous cycle in gonadally intact female mice. Higher expression of Cux2 and Cyp4a10 was detected in gonadally intact WT females in comparison to gonadally intact WT males and higher expression of Cyp2u1 and Hsd3b5 was detected in gonadally intact WT males in comparison to gonadally intact WT females. There were no sex differences in the expression of studied genes between WT gonadectomised and SF-1 KO mice. The results of our study therefore suggest that sex differences in the liver gene expression of the four studied genes are solely dependent on sex hormones and are not influenced by sex chromosome complement.Key words: sex difference; liver; gene expression; sex steroid hormones; sex chromosomes RAZLIKE MED SPOLOMA V IZRAŽENOSTI GENOV PRI NAVADNIH MIŠIH IN MIŠIH Z IZBITIM GENOM SF-1Razvoj in delovanje jeter sta odvisna od natančne izraženosti genov. Predhodne raziskave so pokazale, da so številni geni v jetrih različno izraženi med spoloma, te razlike pa naj bi bile vsaj delno posledica spolnih razlik v izločanju rastnega hormona. Cilj opisane raziskave je bil proučiti, ali tudi spolni kromosomi vplivajo na spolne razlike v izraženosti genov v jetrih.  V raziskavi smo pri navadnih miših in miših z izbitim genom SF-1 (SF-1 KO) preverili izraženost genov Cyp4a10, Cyp2u1, Cux2 in Hsd3b5, za katere je znano, da se v odraslih jetrih izražajo drugače pri samcih kot pri samicah. Miši SF-1 KO se rodijo brez spolnih žlez in zaradi tega niso nikoli izpostavljene spolnim hormonom, razlike med spoloma v izraženosti genov bi zato pri teh miših kazale na neposreden vpliv spolnih kromosomov. Dodatno smo primerjali med seboj tudi miši, ki smo jim odstranili spolne žleze, ter samice v različnih fazah spolnega cikla. Ugotovili smo višjo izraženost genov Cux2 in Cyp4a10 pri navadnih samicah s spolnimi žlezami v primerjavi z navadnimi samci s spolnimi žlezami. Ugotovili smo tudi višjo izraženost genov Cyp2u1 in Hsd3b5 pri navadnih samcih s spolnimi žlezami v primerjavi z navadnimi samicami s spolnimi žlezami. Nismo pa ugotovili vpliva odstranitve spolnih žlez ali vpliva izbitja gena SF-1 na spolne razlike, saj le-te niso bile prisotne ne med samci in samicami z odstranjenimi spolnimi žlezami kot tudi ne med samci in samicami z izbitim genom SF-1. Ti rezultati kažejo, da so vse razlike med spoloma v izraženosti genov v jetrih popolnoma odvisne od prisotnosti in vpliva spolnih hormonov, ki jih proizvajajo spolne žleze.Ključne besede: spolne razlike; jetra; izraženost genov; spolni hormoni; spolni kromosomi