Bigger, not better

 作者:关灼段     |      日期:2019-03-08 08:07:02
By Philip Cohen in Quebec THE causes of the mysterious ailments that kill some animals produced by IVF, and many baby clones, are at last beginning to emerge. Researchers in Scotland and the US say that abnormal levels of proteins that influence growth are involved. The pioneers of cloning have found that all too often their creations die either late in pregnancy or soon after birth (This Week, 19 December 1998, p 4). Some of the clones are unusually large. This seems to be related to the occasional deaths of animals that have been produced by IVF and cultured as embryos before being implanted—a problem known as large offspring syndrome or dopey calf syndrome. Groups working on cloning and animal IVF have been looking for any unusual patterns of gene activity associated with these deaths. Many have focused on the gene Igf2, which makes a protein called insulin-like growth factor 2 (IGF2). “If people had to put money on one gene, they’d choose Igf2,” says Lorraine Young of the Roslin Institute near Edinburgh, birthplace of Dolly the cloned sheep. High levels of IGF2 in mouse fetuses cause abnormalities similar to large offspring syndrome. Patrick Blondin and his colleagues at North Carolina State University in Raleigh studied the activity of Igf2 in cow fetuses aborted about a quarter of the way through gestation. Some were produced by IVF and cultured before being implanted, while others were conceived by artificial insemination (AI). Igf2 activity in the livers of the IVF fetuses was twice as high as in those produced by AI. By contrast, the Igf2 was about 30 per cent less active in the skeletal muscles of IVF fetuses. “That suggests the IVF procedure somehow reprogrammes the gene,” says Blondin. Young’s team has studied sheep produced by IVF. With colleagues at Roslin and the Scottish Agricultural College in Aberdeen, she implanted embryos that had been cultured under conditions known to cause large offspring syndrome. The researchers removed the fetuses at 125 days, a few weeks from full term, and again compared them with fetuses conceived by AI. Young and her colleagues could find no unusual patterns in levels of IGF2 in the large IVF fetuses. So they looked at IGFBP2, a protein which binds to IGF2. Abnormally large IVF embryos had more of this protein in their blood and livers. Young suspects that the binding protein helps to amplify the effect of IGF2, perhaps by preventing its breakdown in the bloodstream. Both teams believe that their work is only the beginning of the search for the genetic basis of large offspring syndrome: many genes might play a role at different points in development. But the results should serve as a warning to human fertility researchers who are considering culturing embryos to improve chances of achieving pregnancy. “If they aren’t aware of the risks, some of these problems might creep into human IVF,