September 13, 2005

Nitric oxide prevents aging of eggs, extends fertility, according to WSU study in Biochemistry

Nitric oxide, a signaling molecule in the nervous system, appears to slow or reverse the aging of eggs in mouse ovaries. This important discovery may improve assisted reproduction techniques and allow women’s eggs to remain healthy and viable, and increase their chances for fertility and having healthy babies into their 30s and 40s. The finding was published by Wayne State researchers in the Aug. 30 issue of the American Chemical Society’s journal Biochemistry. (vol. 44, pages 11361-11368)

Mammalian oocytes, or eggs, have a limited window of opportunity for optimal fertilization. Eggs removed from the ovaries begin to age rapidly without fertilization. If not fertilized within about six hours, the eggs are more prone to abnormal or insufficient fertilization and have a greater likelihood of chromosomal abnormalities. Exposing these eggs to nitric oxide protects them and may significantly increase their viability for in vitro fertilization, intracytoplasmic sperm injection (ICSI) and nuclear transfer.

“In addition to possibly extending fertility in women, our results suggest that nitric oxide could help prevent chromosome errors during early embryonic development,” said first author Anuradha Goud, Ph.D., research associate in the Department of Obstetrics and Gynecology and at the C.S. Mott Center for Human Growth and Development. Specifically, nitric oxide slowed the hardening of the eggs’ outer shells, halted cortical granule loss, and diminished ooplasmic microtubule dynamics. “These phenomena significantly delay the process of postovulatory aging and improve the quality and health of the egg, leading to better outcomes for reproduction,” Dr. Goud said.

“Eggs from older women may be particularly sensitive to aging after they are released from the ovaries,” said Husam Abu-Soud, Ph.D., associate professor of OB-GYN, and co-author on the study. “As a result, the time available for optimal fertilization of these women’s eggs may be quite a bit shorter than the time frame in younger women. But exposing the eggs to appropriate levels of nitric oxide would extend this fertilizable time window in both old and young women,” he said.

Additional co-authors on the study include Drs. Pravin Goud M.D., Ph.D., and Michael Diamond M.D., who note that although it is unclear how nitric oxide produces these effects exactly, nitric oxide shares phosphodiesterase inhibition and antioxidant properties similar to those of caffeine. An earlier study also suggested that caffeine can delay the aging process of eggs and plays a contributory role as an antioxidant molecule.

Incidentally, Dr Anuradha Goud won a Young Investigator Award for this work when she presented at the Gordon Research Conference in Italy earlier this year. At the meeting, she was congratulated by 1998 Nobel Prize winners Drs. Ferid Murad and Louis Ignarro, who are the experts on the therapeutic effects of nitric oxide. Dr. Pravin Goud, has also received eight national awards including the first place award at the 2005 American College of Obstetricians and Gynecologists annual junior fellow meeting for related work.

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[FIGURE] The presence of increased microtubules and decreased cortical granules indicate aging; the minimal presence of microtubules and intactness of cortical granules indicates egg preservation.

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