Cell and Tissue BiologyCell and Tissue BiologyЦитология0041-37713034-6061The Russian Academy of Sciences66966410.31857/S0041377123010078GLBGPNArticlesСтатьиChanges in the Content of Small Non-Coding RNAs in Spermatozoa as a Possible Mechanism of Transgenerational Transmission of the Effects of Paternal Stress: Experimental ResearchИзменение содержания малых некодирующих рнк в сперматозидах как возможный механизм трансгенерационной передачи эффектов отцовского стресса: экспериментальное исследованиеMalyshevaO. V.МалышеваО. В.omal99@mail.ruPivinaS. G.ПивинаС. Г.omal99@mail.ruPonomarevaE. N.ПономареваЕ. Н.omal99@mail.ruOrdyanN. E.ОрдянН. Э.omal99@mail.ruPavlov Institute of Physiology, Russian Academy of ScienceИнститут физиологии им. И.П. Павлова РАНOtt Institute of Obstetrics, Gynecology, and ReproductologyНаучно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта01012023651283827022025Copyright ©; 2023, О.В. Малышева, С.Г. Пивина, Е.Н. Пономарева, Н.Э. ОрдянCopyright ©; 2023, О.В. Малышева, С.Г. Пивина, Е.Н. Пономарева, Н.Э. Ордян2023О.В. Малышева, С.Г. Пивина, Е.Н. Пономарева, Н.Э. ОрдянО.В. Малышева, С.Г. Пивина, Е.Н. Пономарева, Н.Э. Ордянhttps://journals.eco-vector.com/0041-3771/article/view/669664

It has been proven that the stress of the father can affect the phenotype of offspring, causing somatic, behavioral, hormonal and molecular changes. One of the hypothetical mechanisms responsible for the transmission of paternal effects to offspring may be a change in the spectrum of regulatory non-coding RNAs in spermatozoa. In this paper, we investigated the effect of paternal stress in models of post-traumatic stress disorder (PTSD) and depression on the representation of small RNAs (micro- and piwiRNAs) in the sperm of stressed animals. Male Wistar rats were subjected to stress in two paradigms (“stress–restress” and “learned helplessness”), which leads to the development of PTSD-like and depressive-like states in model animals, respectively. 48 days after the restress, sperm preparations were received and RNA was isolated. The spectrum of small RNAs was studied by NGS sequencing. In males with a PTSD-like condition, a change in the expression of 27 piwi RNAs and 77 microRNAs was detected compared with the control group. Among the targets of these miRNAs, it is possible to identify genes whose products may be involved in such mechanisms of transmission of paternal effects to offspring as changes in DNA methylation, histone modifications and RNA interference (Dnmt3a, Setd5, Hdac1, Mllt10, Mtdh), as well as genes associated with the functioning of insulin-like growth factor 2, the expression of which as previously shown, it is altered in the central nervous system in the offspring of males with a PTSD-like condition (Igf2, Igf2bp2, Igf2r). No changes in the representation of small RNAs were registered in males with a simulated depression-like state. The results indicate a pronounced effect of paternal stress on the spectrum of short non-coding RNAs in sperm cells in rats, however, it depends on the nature of the stress effect.

Доказано, что стресс отца может влиять на фенотип потомков, вызывая соматические, поведенческие, гормональные и молекулярные изменения. Одним из гипотетических механизмов, ответственных за передачу отцовских эффектов потомству, может быть изменение спектра регуляторных некодирующих РНК в сперматозоидах. В настоящей работе мы исследовали влияние стресса отца в моделях посттравматического стрессового расстройства (ПТСР) и депрессии на представленность малых РНК (микро- и piwiРНК) в сперме стрессированных животных. Самцов крыс линии Wistar подвергали стрессу в двух парадигмах (“стресс−рестресс” и “выученная беспомощность”), что приводит к развитию у модельных животных ПТСР-подобного и депрессивно-подобного состояний соответственно. Через 48 суток после рестресса получали препараты сперматозоидов, из которых выделяли РНК. Спектр малых РНК исследовали методом NGS-секвенирования. У самцов с ПТСР-подобным состоянием по сравнению с группой контроля было выявлено изменение экспрессии 27 piwiРНК и 77 микроРНК. Среди мишеней этих миРНК можно выделить гены, продукты которых могут быть вовлечены в такие механизмы передачи отцовских эффектов потомству, как изменения метилирования ДНК, модификации гистонов и РНК-интерференции (Dnmt3a, Setd5, Hdac1, Mllt10, Mtdh), а также гены, связанные с функционированием инсулиноподобного фактора роста 2, экспрессия гена которого, как было показано ранее, изменена в ЦНС у потомства самцов с ПТСР-подобным состоянием (Igf2, Igf2bp2, Igf2r). У самцов со смоделированным депрессивноподобным состоянием изменений представленности малых РНК не зарегистрировано. Полученные результаты свидетельствуют о выраженном влиянии стресса отца на спектр коротких некодирующих РНК в сперматозоидах у крыс, однако это влияние зависит от характера стрессового воздействия.

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