Testis cord differentiation after the sex determination stage is independent of Sox9 but fails in the combined absence of Sox9 and Sox8

摘要

emSox9/emandemSox8/emaretranscriptionfactorsexpressedinembryonicandpostnatalSertolicellsofthemousetestis.emSox9/eminactivationpriortothesexdeterminationstageleadstocompleteXYsexreversal.Incontrast,thereisnormalembryonictestisdevelopmentinemSox8/emmutantswhichareinitiallyfertile,butlaterdevelopprogressiveseminiferoustubulefailureandinfertility.TodeterminewhetheremSox9/emisrequiredfortestisdevelopmentaftertheinitialstepsofsexdetermination,wecrossedemSox9/emsupemflox/em/supmicewithanemAMH-Cre/emtransgeniclinetherebycompletelydeletingemSox9/eminSertolicellsbyE14.0.ConditionalemSox9/emnullmutantsshownormalembryonictestisdevelopmentandareinitiallyfertile,but,likeemSox8supminus;/minus;/sup/emmutants,becomesterilefromdysfunctionalspermatogenesisatabout5nbsp;months.ToseewhetheremSox8/emmaycompensatefortheabsenceofemSox9/emduringembryonictestisdifferentiation,wegeneratedaemSox9/emconditionalknockoutonaemSox8/emmutantbackground.Inthedoublemutants,differentiationoftestiscordsintoseminiferoustestistubulesceasesafterP6intheabsenceofoneemSox8/emallele,andafterP0intheabsenceofbothemSox8/emalleles,leadingtocompleteprimaryinfertility.emSox9,Sox8/emdoublenullizygoustestesshowupregulationofearlyovary-specificmarkersanddownregulationofSertoliintercellularjunctionsatE15.5.TheirverylowemAmh/emlevelsstillcausecompleteregressionoftheMuuml;llerianductbutwithreducedpenetrance.ThisstudyshowsthattestiscorddifferentiationisindependentofemSox9/em,andthatconcertedemSox9/emandemSox8/emfunctioninpostE14.0Sertolicellsisessentialforthemaintenanceoftesticularfunction./p/div