A single gene of the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers have observed this in so-called knockout mice that were specifically modified for this purpose. These mice lack the gene for the transcription factor Math6. By conducting further analyses, the research team is now hoping to gain new insights into the role the gene plays in recurrent miscarriage in humans. The researchers published their results in the journal Scientific Reports.
Transcription factors regulate the expression of downstream genes. Math6 plays a significant role in a number of organs during prenatal development as well as in the adult organism. The knockout mice generated lack the gene for the transcription factor Math6. The team successfully demonstrated that - contrary to previous assumptions - embryonic development is not disrupted when Math6 is switched off. "However, embryos and foetuses die due to placenta problems," says the researcher. The development of the placenta, which is made up from maternal and foetal tissue, is vital for supplying the embryos resp. foetuses with nutrients during pregnancy.
In a first step, the research team successfully localised the expression of Math6 in the placenta of mice during different stages of gestation and measured its volumes. In the process, it emerged that the gene activity spikes at the beginning of pregnancy.
In the Math6 knockout mouse, it is in particular the maternal portion of the placenta that presents deficiencies. "Its shape is altered and fewer blood vessels are formed," describes first-time author. As a result, haemorrhaging occurs during pregnancy, resulting in foetal death.
By cross-mating mice, researchers noticed that this disorder occurs only if the pregnant female lacks both parental copies of the Math6 gene. When the researchers mated females lacking only one copy of the gene with males lacking both copies, the placenta formed in the normal way.
"Consequently, the disorder depends on the genetic makeup of the mother, not on that of the embryos," concludes the researchers. "Math6 expression in the female appears to be essential to sustain pregnancy and supply the foetuses with nutrients. The fact that one single gene of the mother plays such a crucial role for placental development is a very rare, but very important observation," continues the researcher.
The project has laid the foundation for further studies of the placenta. In the future, the researchers intend to analyse the underlying mechanism in-depth, in order to gain a better understanding of complications and of recurrent pregnancy loss in humans.
http://news.rub.de/english/press-releases/2018-10-19-medicine-single-missing-gene-leads-miscarriage
https://www.nature.com/articles/s41598-018-33387-x
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