Chronic stress affected sperm through extracellular vesicles

Scientists have discovered a mechanism for epigenetic influence of stress on sperm and the development of a fetus. In response to chronic stress in the extracellular vesicles of epithelial cells of the epididymis has changed the composition of microRNAs and proteins, these structures in turn affect the sperm microRNA that were observed in the sperm of humans and mice. Such effects have evolved over a long period of stress and influenced the development of the nervous system and the stress response in offspring. Article published in the journal Nature Communications.

Conditions, where developing germ cells before conception, significantly influenced the development of the fetus. The adverse conditions in which there is the body, be it stress, diet or drugs, the sperm found in several previous studies. However, the mechanism of this interaction remained unknown.

Mediators of stress effects can be molecules that detect in the semen, for example, small non-coding RNAS. However, after spermatogenesis in the germ cells does not occur transcription, and their DNA is compactly folded to protect from damage. Hence, there is an external, somatic, mechanisms that would have a lasting effect on the sperm development of the embryo.

After spermatogenesis, germ cells continue to form in the tubules of the epididymis, where they receive somatic signals from the surrounding tissue. Right here, through the epithelial cells of the epididymis, a condition in which there is the body, can affect the maturation of sperm.

One of the ways of intercellular communication by extracellular vesicles. This is a small vesicles, which carry proteins, lipids or small non-coding RNA from one cell to another. Extracellular vesicles are intermediaries between the epithelial cells of head of epididymis and the sperm they transmit signals that are important for the maturation of sperm. So the body adapts to the condition of germ cells and subsequent development of the embryo to changing environmental conditions.

Jennifer Chan (Jennifer Chan) at the University of Pennsylvania and her colleagues examined the short-and long-term effects of stress on semen and descendants of mice. Males during the month were put into a state of chronic stress and one or 12 weeks mated them with females. Were then evaluated, as the offspring of these animals to cope with stress. At the same time intervals in mice took sperm samples and was analyzed in a set of microRNAs.

To compare the observed patterns in mice with a human, the researchers examined sperm samples 18 students of the University of Pennsylvania. The volunteers were tested on a monthly basis and at the same time passed a psychological examination, which including the determined stress level. According to the results of psychological tests have identified four students, the stress level which was high at baseline and decreased significantly for six months, and four whose stress levels remained constant throughout the experiment.

Since the effect of stress was observed in the experiment was for a long time, the authors suggested that somatic epidermal cells of the epididymis occur restructuring of chromatin. To test this, using mass spectrometry investigated posttranslational modifications of histones (proteins responsible for the packing of chromatin and regulate other nuclear processes).

In heterogeneous tissues in a living organism is impossible to detect extracellular vesicles, which secrete it epithelial cells of the epididymis. So scientists have reproduced stressful impact on the culture of these cells. To do this in three days on Wednesday added corticosterone, a hormone released under stress. At various intervals thereafter were sampled extracellular vessel and analyzed them in the composition of microRNAs and proteins. Then vesicles were labeled with a dye and injected into mice that did not participate in the experiment to find out the target of extracellular vesicles the epididymis in the body.

The researchers also tested how the impact of extracellular vesicles on sperm affect the development of the embryo. To do this, sperm cells were grown on medium to which were added the extracellular vesicles of epithelial cells of the epididymis. To the half of the vesicles before that for three days, added corticosterone and then gave eight days for the development of the response, the second half was a control. The spermatozoa were injected into oocytes in females, and the embryos implanted in the same mice. In the middle of pregnancy the animals were killed and studied fetal tissue.

Mouse, who was conceived a week after prolonged stress, did not differ from controls. But if males were allowed to develop a response, their descendants have reacted to the stress increased levels of corticosterone. A week after exposure to the composition of microRNAs in the sperm and histone modifications of the epithelium of the epididymis did not differ from controls, and after 12 weeks, the differences became significant.

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