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Environmental Factor, August 2015

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Researchers identify protein that helps prepare healthy egg-sperm union

By Robin Mackar

Headshot of Carmen Williams

Williams leads the NIEHS Reproductive Medicine Group, which focuses on the basic reproductive biology of early mammalian embryo formation. The team focuses on questions related to human reproduction and how it is influenced by the environment. (Photo courtesy of Steve McCaw)

Researchers in the NIEHS Reproductive Medicine Group have discovered a protein that plays a vital role in a healthy egg-sperm union. An embryo cannot survive without male chromosomes, and the protein RGS2 can delay an egg’s development into an embryo, which allows time for sperm to arrive and merge with the egg in a healthy fertilization process.

“These findings show the critical role that the protein RGS2 plays in preserving the fertilizability of the ovulated egg,” said Carmen Williams, M.D., Ph.D., a lead author on the paper, published online in the journal Development. “Other researchers have shown that RGS2 plays an important role in regulating heart function and blood pressure, but this is the first demonstration of the protein’s significant role in fertilization.”

The maturing egg

Williams explained that an immature egg found in the ovary is not very good at rallying the necessary calcium signaling that is needed to respond to sperm. However, during the maturation process, the egg stores calcium, preparing it for fertilization. At fertilization, the sperm causes calcium to be released in the egg, turning it into a developing embryo (see diagram below).

The mouse study shows that during maturation the egg synthesizes RGS2, which suppresses calcium signaling. This safety mechanism ensures that the egg does not begin releasing calcium and start developing before the sperm arrives. Beginning development too early prevents the egg from merging with the sperm.

Therapeutic use

The RGS2 protein is also being studied as a therapeutic target for hypertension and other heart ailments.

“Understanding the role RGS2 plays in reproduction is important when considering the possible benefits and side effects of any new treatments, as well as understanding the impact that toxins might have on human fertility,” said Linda Birnbaum, Ph.D., director of NIEHS and the National Toxicology Program.

Citation: Bernhardt ML, Lowther KM, Padilla-Banks E, McDonough CE, Lee KN, Evsikov AV, Uliasz TF, Chidiac P, Williams CJ, Mehlmann LM. Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs. Development; doi: 10.1242/dev.121707 [Online 9 July 2015].

(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison and a frequent contributor to the Environmental Factor.)

Williams Schematic

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