vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-86vavilov-4351Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSРаспространенность микроделеций AZFc региона Y-хромосомы и влияние на сперматогенез у российских мужчин из общей популяцииPrevalence of AZFс Y chromosome microdeletions and association with spermatogenesis in Russian men from the general populationhttps://orcid.org/0000-0002-7597-9204ОсадчукЛ. В.OsadchukL. V.

Новосибирск

Novosibirsk

losadch@bionet.nsc.ruhttps://orcid.org/0000-0003-0929-6832ВасильевГ. В.VasilievG. V.

Новосибирск

Novosibirsk

ИвановМ. К.IvanovM. K.

р. п. Кольцово, Новосибирская область

Novosibirsk region

ПрасоловаМ. А.PrasolovaM. A.

Новосибирск

р. п. Кольцово, Новосибирская область

Novosibirsk

Novosibirsk region

https://orcid.org/0000-0002-7537-2525КлещевМ. А.KleshchevM. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-4210-7354ОсадчукА. В.OsadchukA. V.

Новосибирск

Novosibirsk

Федеральный исследовательский центр, Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationАО «Вектор-Бест»РоссияJoint Stock Company Vector BestRussian FederationФедеральный исследовательский центр, Институт цитологии и генетики Сибирского отделения Российской академии наук; АО «Вектор-Бест»РоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Joint Stock Company Vector BestRussian Federation202422112024287780791Copyright © Осадчук Л.В., Васильев Г.В., Иванов М.К., Прасолова М.А., Клещев М.А., Осадчук А.В., 20242024Осадчук Л.В., Васильев Г.В., Иванов М.К., Прасолова М.А., Клещев М.А., Осадчук А.В.Osadchuk L.V., Vasiliev G.V., Ivanov M.K., Prasolova M.A., Kleshchev M.A., Osadchuk A.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4351

Y-хромосома содержит набор генов, имеющих тестис-специфическую экспрессию, ответственных за развитие яичек и сперматогенез, и является наиболее важной мишенью в поиске генетических причин мужского бесплодия. Большинство из этих генов расположены в локусе «фактора азооспермии» AZF (регионы AZFa, AZFb и AZFc) на длинном плече Y-хромосомы. Микроделеции Y-хромосомы, приводящие к удалению всего локуса AZF, а также одного или нескольких регионов (полные делеции), являются одной из ведущих причин нарушения сперматогенеза и бесплодия, однако роль частичных AZFc-делеций (gr/gr, b2/b3, b1/b3) в нарушении сперматогенеза не ясна, а влияние на сперматогенез варьирует между популяциями. Цель настоящего исследования состояла в оценке частоты различных типов AZFс-микроделеций и поиске ассоциаций с параметрами сперматогенеза у мужчин славянской этнической группы из общей российской популяции (n = 700, средний возраст 25.8  года). Для выявления AZF-микроделеций анализировали наличие/отсутствие 15 STS-маркеров методом мультиплексной полимеразной цепной реакции в режиме реального времени. У всех участников записывали возраст, вес, рост, оценивали объем, концентрацию, общее количество, долю подвижных и морфологически нормальных сперматозоидов в эякуляте. В исследуемой выборке выявлены 19.9 % (139/700) мужчин с микроделециями AZFс региона, из них 16.7 % (117/700) являлись носителями частичной делеции b2/b3, 3.0 % (21/700) – частичной делеции gr/gr, 0.14 % (1/700) – полной делеции b2/b4. Не обнаружены AZFa и AZFb микроделеции и другие типы AZF-делеций. Суммарная частота всех типов AZFс-делеций, а также каждого типа частичных микроделеций b2/b3 и gr/gr не различалась в группах азооспермии, тяжелой олигозооспермии (≤5.0 млн/мл), олигозооспермии (5.0 < КС < 16.0 млн/мл) и нормальной концентрации сперматозоидов (≥16.0 млн/мл). Сравнение спермиологических показателей в группах с различными типами частичных AZFc-делеций и контролем (без делеций) тоже не выявило достоверных различий. Таким образом, частичные AZFc-микроделеции b2/b3 и gr/gr не оказывают существенного влияния на сперматогенез у славянских мужчин. Предполагается, что у славян частичные AZFсмикроделеции b2/b3 и gr/gr фиксированы в Y-гаплогруппе N3 и R1a соответственно, а их негативное влияние на сперматогенез уравновешивается другими генетическими факторами. Установленная в нашей работе более высокая частота частичных AZFc-делеций (19.7 %) у славян по сравнению с европейскими популяциями (7.3 %) также может объясняться широким распространением этих Y-гаплогрупп в славянской популяции России.>< 16.0 млн/мл) и нормальной концентрации сперматозоидов (≥16.0 млн/мл). Сравнение спермиологических показателей в группах с различными типами частичных AZFc-делеций и контролем (без делеций) тоже не выявило достоверных различий. Таким образом, частичные AZFc-микроделеции b2/b3 и gr/gr не оказывают существенного влияния на сперматогенез у славянских мужчин. Предполагается, что у славян частичные AZFсмикроделеции b2/b3 и gr/gr фиксированы в Y-гаплогруппе N3 и R1a соответственно, а их негативное влияние на сперматогенез уравновешивается другими генетическими факторами. Установленная в нашей работе более высокая частота частичных AZFc-делеций (19.7 %) у славян по сравнению с европейскими популяциями (7.3 %) также может объясняться широким распространением этих Y-гаплогрупп в славянской популяции России.

The Y chromosome contains a set of genes with testis-specific expression that are responsible for the development of testes and spermatogenesis, and it is the most important target in the search for genetic causes of male infertility. Most of these genes are located in the “azoospermia factor” AZF locus (regions AZFa, AZFb, and AZFc) on the long arm of the Y chromosome. Microdeletions of the Y chromosome, leading to the removal of the entire AZF locus as well as one or more regions (complete deletions), are one of the leading causes of spermatogenesis impairment and infertility. However, the role of partial AZFc deletions (gr/gr, b2/b3, b1/b3) in spermatogenesis failure is unclear, and their impact on spermatogenesis varies between populations. The aim of the present study was to assess the frequency of various types of AZFc microdeletions and to search for associations with spermatogenesis parameters in men of Slavic ethnicity from the general Russian population (n = 700, average age 25.8 years). To identify AZF microdeletions, the presence/ absence of 15 STS markers was analyzed using multiplex real-time polymerase chain reaction. Age, weight, height, and the volume, concentration, total count, proportion of motile and morphologically normal spermatozoa in the ejaculate were recorded for all participants. In the studied sample, 19.9 % (139/700) of men were found to have AZFc microdeletions, of which 16.7 % (117/700) were carriers of a partial b2/b3 deletion, 3.0 % (21/700) had a partial gr/gr deletion, and 0.14 % (1/700) had a complete b2/b4 deletion. Neither AZFa nor AZFb microdeletions nor other types of AZF deletions were detected. The overall frequency of all types of AZFc deletions, as well as each type of partial microdeletion, b2/b3 and gr/gr, did not differ in the groups of azoospermia, severe oligozoospermia (≤5.0 mill/ml), oligozoospermia (5.0 < SC < 16.0 mill/ml), and normal sperm concentration (≥16.0 mill/ml). Comparison of semen parameters in groups with different types of partial AZFc deletions and the control group (without deletions) also did not reveal significant differences. Thus, partial AZFc microdeletions b2/b3 and gr/gr do not have a significant impact on spermatogenesis in Slavic men. It is suggested that in Slavs, partial AZFc microdeletions b2/b3 and gr/gr are fixed in Y haplogroups N3 and R1a, respectively, and their negative impact on spermatogenesis is balanced by other genetic factors. The higher frequency of partial AZFc deletions (19.7 %) in Slavs compared to European populations (7.3 %) established in our study may be explained by the widespread distribution of these Y haplogroups in the Slavic population of Russia.

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The authors declare that there are no conflicts of interest present.