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Scripps research scientists identify infertility molecule

GPCRs.

In the last few years, Chun and his colleagues have been pursuing basic research on LPA and its receptors to try to understand their roles, particularly in the brain -- looking, for instance, at the effect of LPA on mammalian brain development. Recently, they showed that LPA can induce neurogenesis­the formation of new neurons -- in mice, and can also participate in neuropathic pain models.

Wanting to go further, they created what is known as a knock-out mouse model for a specific LPA receptor. These are special mice that lack one or more particular genes of interest -- in this case, a gene that encodes a particular LPA receptor called LPA3. With such a model, scientists can determine some of the overall physiological effects of an LPA receptor protein.

Creation of LPA receptor knock-out mice for LPA3 produced a surprising phenotype -- fertility problems. Analyses revealed that the spacing of the embryos in the womb was altered, and the number of implanted embryos was reduced (mice have litters of pups, typically giving birth to eight or so offspring with each pregnancy). Also, instead of the normal types of implantation, the embryos were clustered and many of them ended up sharing a placenta.

"Here is a clear effect on the ability of embryos to implant and position normally," says Chun. "[It identifies] a new molecular influence­a small fat molecule­on this whole process."

Chun, Ye, and their colleagues went on to show that losing LPA receptors affected prostaglandin levels. Prostaglandin is a fatty acid found in mammals that is essential for normal implantation. Manipulating parts of LPA signaling may thus be a way of changing prostaglandin levels.

This is a significant finding because low implantation rates are one of the major issues facing women who use assisted reproductive technologies, and nobody has ever considered LPA signaling to be involved in implantation. If the same pathway turns out to be relevan
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Source:Scripps Research Institute


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