By studying male mice suffering from depression, Chinese researchers found that they were able to pass these traits on to their offspring. Not through genes, but through the genetic material encoded in their semen.
- Hereditary depression is not due to genes, but to sperm microRNAs.
- The study conducted on depressed male mice shows that sperm microRNAs can receive signals from the paternal environment. These signals are then integrated into the genetic profiles of the zygotes.
- This discovery paves the way for potential development of antidepressant treatments.
One of the most common mental disorders the Depression is it really transmitted to its children by the genes?
While many studies have already looked at the hereditary nature of depression, a new study published in the journal Science Advances by researchers at the Nanjing Medical University (China) provides new answers and overturns what we thought we knew until now. According to them, depression is not transmitted genetically but via epigenetic alterations. These genetic changes do not alter the base sequence of DNA, but affect the way cells express this DNA by chemical conversion, into RNA and then into proteins. “We show that offspring of depressed fathers develop increased susceptibility to depression when exposed to mild stress, and that sperm RNAs (especially microRNAs) play a causal role in the heredity of depression. Such a mechanism of epigenetic germline inheritance opens a new avenue to fill the gap in our knowledge of the pathophysiology of depression.”explains Xi Chen, lead author of the work.
Transmission by sperm microRNAs
To conduct their research, the scientists subjected male mice to stressful experiments to induce depressive behavior in them. These male mice were then mated with unstressed female mice. The newborn pups showed no biological differences compared to those from healthy male mice. However, when the researchers subjected the offspring to mild stress experiments, the latter adopted the same behavioral changes in response as their parent.
The researchers therefore sought to understand how the depressed mice had transmitted their behavior to their offspring. By examining the sperm of the male mice, they found that there were changes in the genetic content. They isolated all non-coding RNA from sperm and injected it into a healthy zygote. The latter then implanted in a carrier mouse. The mice born from the experiment were also sensitive to depression.
The team, on the other hand, showed that when the observed stress-induced changes in RNA were blocked, the offspring did not inherit the depressive behavior of its progenitor. “Although previously thought to be negligible remnants of spermatogenesis, sperm RNAs (specifically microRNAs) are shown here to transmit paternal depression to offspring. Mechanically, sperm RNAs can receive cues from the environment paternal, then reshaping genetic profiles in zygotes, thereby inducing a cascading change during early embryonic development, details Professor Chen. Thus, life experiences and environmental cues (e.g., stress) can be stored in sperm RNAs as epigenetic information for intergenerational communication.”
According to him, these results could “offer a new dimension for the development of new antidepressant treatments”. However, many steps are necessary for this work to be applicable to humans. “Our next step is to explore the potential roles of human sperm microRNAs in depression. We have already contacted several hospitals and have begun to assess the scope of ethical clearance to measure sperm microRNA profiles in patients with depression. depression”concludes the scientist.
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