Ferro Mísia Helena da Silva, Morante Ingrid, Nishino Fernanda Akane, Estevam Camila, do Amaral Fernanda Gaspar, Cipolla-Neto José, Stumpp Taiza
Laboratory of Developmental Biology, Department of Morphology and Genetics-Paulista Medicine School, Federal University of Sao Paulo (UNIFESP), Sao Paulo, SP, Brazil.
Department of Physiology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
PLoS One. 2025 Jan 27;20(1):e0312403. doi: 10.1371/journal.pone.0312403. eCollection 2025.
Melatonin is a pineal hormone synthesized exclusively at night, in several organisms. Its action on sperm is of particular interest, since they transfer genetic and epigenetic information to the offspring, including microRNAs, configuring a mechanism of paternal epigenetic inheritance. MicroRNAs are known to participate in a wide variety of mechanisms in basically all cells and tissues, including the brain and the sperm cells, which are known, respectively, to present 70% of all identified microRNAs and to transfer these molecules to the embryo. MicroRNAs from sperm have been associated with modulation of embryonic development and inheritance of psychiatric symptoms, including autism. Given that microRNAs and melatonin are ubiquitous molecules with important roles in the organism, the aim of this study was to investigate the expression of specific microRNAs in sperm, brain and cerebellum of pinealectomized rats. For this study, Wistar rats had their pineal gland removed at 60 post-partum. Part of these rats received exogenous melatonin until the day of the euthanasia. The control group did not receive any treatment or manipulation. The sperm, hypothalamus, prefrontal cortex and cerebellum were collected for analysis of microRNA expression by RT-qPCR. The results suggest that melatonin absence caused by pinealectomy increases the expression of the target microRNAs in the sperm. Although the data suggest an alteration (increase or decrease depending on the region and microRNA) of expression levels of some microRNAs in the brain and cerebellum of pinealectomized rats, the differences were not statistically significant. This seems to be a consequence of the intragroup variation. Melatonin administration restored the levels of the target microRNAs in the sperm. Additional studies are needed to understand the impact of the alterations of microRNA expression to the pinealectomized rats as well as to their descendants.
褪黑素是一种仅在夜间于多种生物体中合成的松果体激素。它对精子的作用尤为令人关注，因为精子会将遗传和表观遗传信息传递给后代，包括微小RNA，从而构成一种父系表观遗传遗传机制。众所周知，微小RNA参与了基本上所有细胞和组织中的多种机制，包括大脑和精子细胞，已知大脑中存在所有已鉴定微小RNA的70%，而精子细胞会将这些分子传递给胚胎。来自精子的微小RNA与胚胎发育的调节以及包括自闭症在内的精神症状的遗传有关。鉴于微小RNA和褪黑素是在生物体中具有重要作用的普遍存在的分子，本研究的目的是调查松果体切除大鼠的精子、大脑和小脑中特定微小RNA的表达情况。在本研究中，Wistar大鼠在产后60天切除松果体。其中部分大鼠在安乐死当天之前接受外源性褪黑素。对照组未接受任何治疗或操作。收集精子、下丘脑、前额叶皮质和小脑，通过RT-qPCR分析微小RNA表达。结果表明，松果体切除导致的褪黑素缺失会增加精子中靶微小RNA的表达。尽管数据表明松果体切除大鼠的大脑和小脑中某些微小RNA的表达水平发生了改变（根据区域和微小RNA的不同而增加或减少），但差异无统计学意义。这似乎是组内变异的结果。给予褪黑素可恢复精子中靶微小RNA的水平。需要进一步的研究来了解微小RNA表达改变对松果体切除大鼠及其后代的影响。
