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Changes in Content of Small Noncoding RNA in Spermatozoa as a Possible Mechanism of Transgenerational Transmission of Paternal Stress Effect: An Experimental Study

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Abstract

It has been proved that paternal stress can affect the phenotype of offspring, inducing somatic, behavioral, hormonal, and molecular changes. One hypothetical mechanism responsible for the transmission of paternal effects to offspring is an altered spectrum of regulatory noncoding RNAs in spermatozoa. In the present work, we investigated the effect of paternal stress in models of posttraumatic stress disorder (PTSD) and depression on the spectrum of small RNA (micro- and piwiRNAs) in the sperm of stressed animals. Male Wistar rats were subjected to stress in two paradigms (“stress–restress” and “learned helplessness”), resulted in the development of PTSD- and depression-like states in model animals, respectively. Forty-eight days after the restress, RNA was isolated from obtained sperm preparations. The spectrum of small RNAs was examined by next-generation sequencing (NGS). In males with a PTSD-like state, altered expression of 27 piwiRNAs and 77 microRNAs was revealed compared with the control group. Among the targets of these microRNAs, one can distinguish genes the products of which 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, and Mtdh), as well as genes associated with the functioning of insulin-like growth factor 2, the expression of which is changed in the CNS in the offspring of males with a PTSD-like state (Igf2, Igf2bp2, and Igf2r). In males with a simulated depression-like state, no changes in the representation of small RNAs were registered. The results obtained demonstrate that paternal stress has a pronounced effect on the spectrum of short noncoding RNAs in spermatozoa in rats, however, this effect depends on the nature of the stress effect.

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Funding

The work was carried out within the framework of a state order to the Pavlov Institute of Physiology, Russian Academy of Sciences, and Ott Research Institute of Obstetrics, Gynecology and Reproductology , FNI subject no. AAAA-A19-119021290033-1.

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Authors and Affiliations

  1. Pavlov Institute of Physiology, Russian Academy of Sciences, 199034, St. Petersburg, Russia

    O. V. Malysheva, S. G. Pivina & N. E. Ordyan

  2. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, St. Petersburg, Russia

    O. V. Malysheva & E. N. Ponomareva

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  1. O. V. Malysheva
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  2. S. G. Pivina
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  3. E. N. Ponomareva
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Correspondence to O. V. Malysheva.

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Statement on the welfare of animals. The work was carried out in compliance with recommendations on the ethics of working with animals approved by the legal acts of the Russian Federation, the principles of the Basel Declaration, and the recommendations of the Commission for the Humane Treatment of Animals of the Pavlov Institute of Physiology, Russian Academy of Sciences.

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Abbreviations: DLS—depression-like state; PTSD—posttraumatic stress disorder; ELISA—enzyme immunoassay.

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Malysheva, O.V., Pivina, S.G., Ponomareva, E.N. et al. Changes in Content of Small Noncoding RNA in Spermatozoa as a Possible Mechanism of Transgenerational Transmission of Paternal Stress Effect: An Experimental Study. Cell Tiss. Biol. 17, 223–232 (2023). https://doi.org/10.1134/S1990519X23030070

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