vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.376vavilov-1543Research ArticleФИЗИОЛОГИЧЕСКАЯ ГЕНЕТИКАPHYSIOLOGICAL GENETICSГЕНДЕР-СПЕЦИФИЧЕСКОЕ ВЛИЯНИЕ МУТАЦИИ Аy У МЫШЕЙ НА МЕТАБОЛИЧЕСКИЙ ФЕНОТИП ПОТОМСТВА, РОСТ ПЛОДОВ И ЭКСПРЕССИЮ ГЕНОВ В ПЛАЦЕНТАХGENDER-SPECIFIC INFLUENCE OF Aу MUTATION ON PROGENY METABOLIC PHENOTYPE, FETAL GROWTH AND PLACENTAL GENE EXPRESSION IN MICEМакароваЕ. Н.MakarovaE. N.

Новосибирск

Novosibirsk

enmakarova@gmail.comДенисоваЕ. И.DenisovaE. I.

Новосибирск

Novosibirsk

КожевниковаВ. В.KozhevnikovaV. V.

Новосибирск

Novosibirsk

КулешоваА. Е.KuleshovaA. E.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics SB RASRussian Federation201803072018224406414Copyright © Макарова Е.Н., Денисова Е.И., Кожевникова В.В., Кулешова А.Е., 20182018Макарова Е.Н., Денисова Е.И., Кожевникова В.В., Кулешова А.Е.Makarova E.N., Denisova E.I., Kozhevnikova V.V., Kuleshova A.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1543

Ожирение матерей в период беременности повышает риск возникновения ожирения у потомства. Для разработки методов коррекции развития потомства у матерей, страдающих метаболическими расстройствами, необходимо изучение молекулярных механизмов, опосредующих влияние материнской среды на онтогенез потомства. Уровень лептина повышается при ожирении. У мышей линии C57Bl мутация Ау вызывает повышение уровня лептина в крови самок во время беременности и оказывает гендер-специфическое влияние на метаболический фенотип потомства в зрелости. Целью работы было изучить влияние мутации Ау на склонность к развитию диетарного ожирения у мужского и женского потомства, на массу плодов и плацент и экспрессию генов в плацентах плодов разного пола. Оценивали массу тела и потребление пищи у мужского и женского потомства Ау/ɑ и ɑ/ɑ  (контроль) самок при содержании на стандартной диете и диете, индуцирующей ожирение, массу плодов и плацент на 13-й и 18-й дни беременности и экспрессию генов транспортеров глюкозы (GLUT1, GLUT3), нейтральных аминокислот (SNAT1, SNAT2, SNAT4), инсулиноподобного фактора роста 2 IGF2 и его рецептора IGF2R в плацентах плодов мужского и женского пола. Мутация Ау влияла на массу тела только у мужского потомства при содержании на стандартной диете и не оказывала влияния на развитие ожирения у потомства обоего пола. Масса плодов и плацент у Ау/ɑ по сравнению с ɑ/ɑ  самками была снижена на 13-й день беременности и не различалась на 18-й день. На 13-й день беременности  уровень мРНК исследованных генов в плацентах мужских и женских плодов не различался у ɑ/ɑ  самок. У Ау/ɑ самок экспрессия генов, кодирующих GLUT1, GLUT3, SNAT1 и SNAT4, была снижена в плацентах плодов женского пола по сравнению с плацентами плодов мужского пола. Полученные результаты позволяют предполагать, что зависящий от пола плодов транскрипционный ответ плацент на повышенный уровень лептина у беременных Ау/ɑ самок может опосредовать гендер-специфическое влияние мутации Ау на метаболизм потомства в постнатальной жизни.

Obesity during pregnancy increases the risk of obesity in offspring. To correct the offspring development in obese mothers, it is necessary to reveal the molecular mechanisms that mediate the influence of the maternal environment on the offspring ontogenesis. Leptin levels increase with obesity. In C57Bl mice, the Ау mutation is associated with elevated blood levels of leptin in pregnant females and exerts a gender-specific effect on the metabolic phenotype of mature offspring. Aim: to study the influence of Ау mutation on sensitivity to diet-induced obesity in male and female offspring, on fetal and placental weight and on the expression of genes in the placentas of the fetuses of different sexes. Body weight and food intake on a standard and an obesogenic diet, fetal and placental weights on pregnancy days 13 and 18, and gene expression of glucose transporters (GLUT1, GLUT3), neutral amino acid transporters (SNAT1, SNAT2, SNAT4), insulin-like growth factor 2 IGF2 and its receptor IGF2R were measured in male and female offspring of и ɑ/ɑ (control) and Ау/ɑ mothers. Ay mutation influenced the body weight only in male offspring, which consumed a standard diet, and did not influence obesity development in both male and female offspring. The weight of fetuses and placentas in Ау/ɑ as compared to ɑ/ɑ  females was reduced on day 13 of pregnancy and was not different on day 18. On day 13 of pregnancy, the mRNA levels of the examined genes did not differ in placentas of male and female fetuses in ɑ/ɑ  females. In Ау/ɑ females, the gene expression of GLUT1, GLUT3, SNAT1 and SNAT4 was reduced in female placentas compared to male placentas. The results suggest that the sex-specific transcription response of placentas to elevated leptin levels in pregnant Ау/ɑ females can mediate the gender-specific impact of Ау mutation on the offspring metabolism in postnatal life.

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