How do some mammals postpone the development of their embryos to await better conditions for having offspring? A recent study at the UW Medicine Institute for Stem Cell and Regenerative Medicine explored this reproductive enigma, which can occur in more than 130 species of mammals as well as in some marsupials.
The study was study led by Abdiasis Hussein, a graduate student in the lab of Hannele Ruohola-Baker, UW professor of biochemistry and associate director of UW Medicine's Institute for Stem Cell and Regenerative Medicine. The findings were reported in Developmental Cell , a Cell Press scientific journal.
The results not only advance the understanding of delayed embryo implantation, but also suggest how some otherwise rapidly dividing cells, such as those in tumors, become quiescent.
In the suspended state of pregnancy called embryonic diapause, an early-stage embryo refrains from implanting in the mother's uterus, where it could be nourished to grow into a baby. Instead, like a seed, the embryo remains dormant until certain molecular regulators prod it to germinate.
Diapause, or delayed implantation, is a biological strategy for waiting out conditions unfavorable to sustaining newborns, such as lack of food, insufficient maternal fat stores, or older siblings who haven't been weaned.
Bears, armadillos, seals, and some otters, badgers and other weasel-like animals undergo seasonal diapause, as a regular part of their reproductive cycles.
Many types of bears, for example, breed in the late spring or early summer. The female then voraciously hunts for food. Only when the female bear has sufficient body fat and weight will one or more of her embryos implant months later, after she retreats to her den. Any cubs would be born in late winter.
To learn what puts a biochemical hold-and-release on embryonic development, Hussein, Ruohola-Baker and their team induced diapause in a female mouse model by reducing estrogen levels. They then compared diapause embryos to pre-implantation and post-implantation embryos. They also induced diapause in mouse embryonic stem cells by starving the cells, and compared those to actively growing mouse embryonic stem cells.
In the wild, some animal embryos will delay implantation until their mother has enough energy and nutrients in her body to support them. Starvation or other stresses somehow provoke an embryonic stop-time. This response is an effort to protect their survival.
The researchers did extensive studies of how metabolic and signaling pathways control both the dormant and active states of mouse embryos and of mouse embryonic stems cells in lab dishes.
Metabolism concerns the life-sustaining chemical activities cells carry out to convert substances into energy, build materials, and remove waste. By analyzing these reactions' end products, called metabolites, the scientists could begin to pull together a picture of what happens to cause diapause, and how cells are released from its clutches. Related Stories
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