The embryo of a roe deer roe deer develops slowly over many months. The image shows an embryo of a bovine early under the microscope. Credit: scientificazurich/ETH Zurich
Roe deer is one of the few mammals that have embryos that go into prolonged periods of dormancy. ETH Zurich researchers discovered for the first time, using modern molecular techniques, what happens to an embryo during this period. The embryo's awakening is controlled by the signals they have discovered.
Everybody is familiar with the Roe Deer. This majestic creature with big, black eyes is either in crossword puzzles or real-life encounters.
Although roe deer are quite common in Swiss forests, they have a unique characteristic. The pinhead-sized embryo, after fertilization and mating in midsummer, does not become implanted in the uterus. Instead, it enters into an embryonic period, also known as embryonic diapause. This period lasts from December to over four months. The embryo then develops at a normal rate and implants in the uterus. After four and a quarter months of "real" gestation the doe gives birth in May to one to three fawns.
The phenomenon is still a mystery, even though it has been around for over 150 years. Over 130 mammalian species have been confirmed to experience various forms of embryonic diapause. They are not as common as those seen in the roedeer. And most importantly, they are almost impossible to find in any other species that exhibits such a strong, continuous deceleration rather than a complete stop. Scientists can induce diapause in mice. It is not yet clear what factors in the roe deer control diapause and keep the embryo alive.
Susanne Ulbrich is Professor of Animal Physiology at ETH Zurich and has been studying the mystery of roe-deer diapause. Researchers have revealed that embryonic cells still divide in diapause. However, this is a slow process. The number of cells, including embryonic and stem cells, doubles every two to three week. This study was published in the journal PNAS and involved researchers from the ETH group as well as researchers from the Universities Bern and Zurich, as well French and German research institutions.
Study of gene transcripts and signaling molecules
The researchers looked at the molecular makeup of the uterine fluid to answer the question about what stops embryonic cells from growing at normal rates. The transcriptome, which is the sum of all messengerRNA molecules in the embryos and uterine epithelial cell cells, was next examined.
Researchers discovered signaling substances in the uterine fluid that could regulate cell division rates. Particularly prominent was the amino acid serine. Researchers at ETH found that certain amino acids were less concentrated in the uterine fluid after diapause. The cell proliferation rate returns to normal after this time.
This involves the mammalian target for rapamycin (mTOR) molecular complex. mTOR reacts with amino acids and plays a critical role in many metabolic signaling pathways within mammalian cells. This includes those that are associated with cancer. mTORC1 regulates cell growth and division by controlling protein synthesis.
The new findings show that only mTORC1 activity is suppressed in roe-deer embryos during diapause. This contrasts with diapausing mice where cell division is stopped completely by inhibition of both the mTORC1 or mTORC2.
The significant rise in the level of amino acids in the uterine fluid near the end diapause activates mTORC1. This activates mTORC1, which in turn increases the expression levels of cell cycle and metabolic genes, thereby accelerating embryo development. Researchers speculate that cell division slows down in the absence of mTORC2 inhibition during diapause in roe-deer embryos.
Researchers did not examine whether any other signaling molecules were involved in this study. It is not clear if the amino acids actually trigger the resumption embryonic development. Or if the embryo secretes signaling molecules that affect maternal cells. Specific signaling molecules may be used by the embryo to indicate its presence to its mother. Ulbrich hopes to fill this knowledge gap through future research.
A new light on reproductive biology
These findings provide new insight into reproductive and developmental biology. How is pregnancy established in mammals is a fundamental question. In domestic cattle and women, for example, embryos fail to implant in their uterus and often die. Ulbrich states that this is due to complex interactions between the embryos and their mothers.
She also said that timing is key to a successful pregnancy. The embryo must communicate with the mother at the appropriate time using molecular signals. Ulbrich says, "We want to understand the interaction between embryos and mothers." Ulbrich says the ideal model for this is the roedeer. The roe-deer embryonic development is similar to that of cattle, but it takes place in slow motion. This allows us to more temporally resolve sequences of events and discover causal relationships.
These findings may also be used to improve in vitro fertilization for humans, so embryos might no longer have to be frozen. Natural factors, such as embryonic stem cells and embryonic stem cells could also be used to regulate the rate of cell division.
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More information: Amino acid activates mTORC1 to free roe-deer embryos decelerated during diapause. PNAS, publiziert 27.8.2021. Publication 27.8.2021. DOI: 10.1073/pnas.2100500118 Trophectoderm and embryoblast proliferate at slow pace in the course of embryonic diapause in the roe deer (Capreolus capreolus) (2020). Bioscientifica Proceedings 10 ISEDISED13 | DOI: 10.1530/biosciprocs.10.013 Journal information: Proceedings of the National Academy of Sciences
