{"id":4201,"date":"2022-05-06T08:02:45","date_gmt":"2022-05-06T06:02:45","guid":{"rendered":"https:\/\/www.mc-praha.cz\/mcp\/?p=4201"},"modified":"2022-08-10T13:09:41","modified_gmt":"2022-08-10T11:09:41","slug":"vytvorily-si-oocyty-strategii-jak-zabranit-vzniku-mitochondrialnich-mutaci","status":"publish","type":"post","link":"https:\/\/www.mc-praha.cz\/mcp\/vytvorily-si-oocyty-strategii-jak-zabranit-vzniku-mitochondrialnich-mutaci\/","title":{"rendered":"S v\u011bkem p\u0159ib\u00fdvaj\u00edc\u00ed mutace v mtDNA \u017eensk\u00fdch oocyt\u016f limituj\u00ed reprodukci"},"content":{"rendered":"<p><em>Mutace v mitochondri\u00e1ln\u00ed DNA (mtDNA) se s\u00a0v\u011bkem hromad\u00ed a zp\u016fsobuj\u00ed mnoh\u00e1 genetick\u00e1 onemocn\u011bn\u00ed. Kv\u016fli vysok\u00e9 chybovosti sou\u010dasn\u00fdch sekvena\u010dn\u00edch technologi\u00ed v\u0161ak z\u016fst\u00e1v\u00e1 problematika mitochondri\u00e1ln\u00edch mutac\u00ed nedostate\u010dn\u011b prozkoum\u00e1na. Ned\u00e1vno v\u011bdci do\u0161li k\u00a0p\u0159ekvapiv\u00e9mu zji\u0161t\u011bn\u00ed, \u017ee si oocyty star\u0161\u00edch samic makak\u016f vytvo\u0159ily obrann\u00fd mechanismus zabra\u0148uj\u00edc\u00ed tvorb\u011b mutac\u00ed. To je zaj\u00edmav\u00fd poznatek ve srovn\u00e1n\u00ed s\u00a0v\u011bkem rapidn\u011b se akumuluj\u00edc\u00edmi mutacemi v \u017eensk\u00fdch oocytech. V\u00fdzkum c\u00edl\u00ed na tuto problematiku mj. vzhledem k sou\u010dasn\u00e9mu trendu odkl\u00e1dat po\u010det\u00ed potomk\u016f do pozd\u011bj\u0161\u00edho v\u011bku. \u00a0<\/em><\/p>\n<p>Arbeithuber et al. (2022) se zam\u011b\u0159ili na samice makaka rhesus jako na modelov\u00fd organismus pro v\u00fdzkum mutac\u00ed v mtDNA. S vyu\u017eit\u00edm duplexn\u00edho sekvenov\u00e1n\u00ed zkoumali akumulace mutac\u00ed souvisej\u00edc\u00ed s v\u011bkem v z\u00e1rode\u010dn\u00fdch a somatick\u00fdch bu\u0148k\u00e1ch. Byly analyzov\u00e1ny mutace v oocytech samic r\u016fzn\u00fdch v\u011bkov\u00fdch skupin \u2013 od t\u011bch, kter\u00e9 je\u0161t\u011b nedos\u00e1hly pohlavn\u00ed dosp\u011blosti (1\u20133 roky), a\u017e po samice v menopauze (23 let).<\/p>\n<p>Duplexn\u00ed sekvenov\u00e1n\u00ed pomoc\u00ed dvou templ\u00e1tov\u00fdch \u0159et\u011bzc\u016f DNA sni\u017euje chybovost anal\u00fdzy o n\u011bkolik \u0159\u00e1d\u016f. Touto metodou byla z\u00edsk\u00e1na data vysoce kvalitn\u00ed sekvence mtDNA somatick\u00fdch tk\u00e1n\u00ed (j\u00e1tra a kostern\u00ed svalstvo) a jednotliv\u00fdch oocyt\u016f.<\/p>\n<p>Celkem bylo identifikov\u00e1no 17 637 tk\u00e1\u0148ov\u011b specifick\u00fdch de novo mutac\u00ed. Jejich frekvence byla v j\u00e1trech 3,5\u00d7 vy\u0161\u0161\u00ed a v oocytech 2,5\u00d7 vy\u0161\u0161\u00ed ne\u017e v\u00a0ostatn\u00edch bu\u0148k\u00e1ch.<\/p>\n<p>U oocyt\u016f byl zji\u0161t\u011bn zvy\u0161uj\u00edc\u00ed se po\u010det mutac\u00ed pouze do v\u011bku 9 let, pot\u00e9 u\u017e skoro nevznikaj\u00ed. To nazna\u010duje, \u017ee oocyty star\u0161\u00edch samic makak\u016f si zachov\u00e1vaj\u00ed kvalitu sv\u00e9 mtDNA. Z\u016fst\u00e1v\u00e1 ot\u00e1zkou, pro\u010d k\u00a0takov\u00e9mu z\u00e1sadn\u00edmu zvratu a ukon\u010den\u00ed tvorby mutac\u00ed doch\u00e1z\u00ed v\u00a0oocytech samic zrovna ve v\u011bku 9 let.<\/p>\n<p>U star\u0161\u00edch zv\u00ed\u0159at mohou b\u00fdt mitochondrie s vysok\u00fdm po\u010dtem \u0161kodliv\u00fdch mutac\u00ed odstran\u011bny mitof\u00e1gi\u00ed, nebo oocyty s vysokou muta\u010dn\u00ed z\u00e1t\u011b\u017e\u00ed mtDNA mohou b\u00fdt eliminov\u00e1ny folikul\u00e1rn\u00ed atr\u00e9zi\u00ed.<\/p>\n<p>Akumulaci z\u00e1rode\u010dn\u00fdch mutac\u00ed mtDNA souvisej\u00edc\u00ed s v\u011bkem v oocytech samic makak\u016f v\u011bdci porovn\u00e1vali s\u00a0v\u00fdsledky nep\u0159\u00edm\u00e9ho pozorov\u00e1n\u00ed u lid\u00ed. Zde je patrn\u00fd zv\u00fd\u0161en\u00fd po\u010det de novo mutac\u00ed u d\u011bt\u00ed star\u0161\u00edch \u017een.<\/p>\n<p>Dal\u0161\u00ed v\u00fdzkum se zam\u011b\u0159\u00ed na p\u0159\u00edm\u00e9 sekvenov\u00e1n\u00ed mutac\u00ed mtDNA oocyt\u016f \u017een r\u016fzn\u00e9ho v\u011bku a m\u011bl by odpov\u011bd\u011bt na ot\u00e1zku, jak se hromad\u00ed z\u00e1rode\u010dn\u00e9 mutace v\u00a0jejich mtDNA.<\/p>\n<p>V Medic\u00ednsk\u00e9m centru Praha V\u00e1m m\u016f\u017eeme nab\u00eddnout otestov\u00e1n\u00ed mitochondri\u00ed na pr\u016ftokov\u00e9m cytometru (stanoven\u00ed procentu\u00e1ln\u00edho po\u010dtu mitochondri\u00ed nach\u00e1zej\u00edc\u00edch se v apopt\u00f3ze), ur\u010den\u00ed Va\u0161\u00ed mitochondri\u00e1ln\u00ed haploskupiny (zji\u0161t\u011bn\u00ed genetick\u00fdch ko\u0159en\u016f z mat\u010diny strany) anebo kompletn\u00ed sekvenaci Va\u0161\u00ed mitochondri\u00e1ln\u00ed DNA.<\/p>\n<p>Ing. V\u00edt Smejkal<\/p>\n<p>29.04. 2022<\/p>\n<p>Zdroj:<\/p>\n<p>Arbeithuber B., Cremona M.A., Hester J., et al. (2022): Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues. Proceedings of the National Academy of Sciences of the United States of America, 119: e2118740119. doi: 10.1073\/pnas.2118740119<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Mutace v mitochondri\u00e1ln\u00ed DNA (mtDNA) se s\u00a0v\u011bkem hromad\u00ed a zp\u016fsobuj\u00ed mnoh\u00e1 genetick\u00e1 onemocn\u011bn\u00ed. Kv\u016fli vysok\u00e9 [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"image","meta":{"_uag_custom_page_level_css":""},"categories":[1],"tags":[],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false,"boldthemes_grid":false,"boldthemes_grid_11":false,"boldthemes_grid_22":false,"boldthemes_grid_21":false,"boldthemes_grid_12":false,"boldthemes_latest_posts":false,"boldthemes_grid_gallery":false},"uagb_author_info":{"display_name":"Jbednar","author_link":"https:\/\/www.mc-praha.cz\/mcp\/author\/jbednar\/"},"uagb_comment_info":0,"uagb_excerpt":"Mutace v mitochondri\u00e1ln\u00ed DNA (mtDNA) se s\u00a0v\u011bkem hromad\u00ed a zp\u016fsobuj\u00ed mnoh\u00e1 genetick\u00e1 onemocn\u011bn\u00ed. Kv\u016fli vysok\u00e9 [&hellip;]","post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4201"}],"collection":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/comments?post=4201"}],"version-history":[{"count":7,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4201\/revisions"}],"predecessor-version":[{"id":4242,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4201\/revisions\/4242"}],"wp:attachment":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/media?parent=4201"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/categories?post=4201"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/tags?post=4201"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}