For millennia, age has implied gradual infertility. As women move closer and closer to menopause, their potential to become pregnant diminishes for a variety of reasons, including slowly diminishing egg quality.1
Delaying Egg Aging
Now, a new study claims a chemical substance known as nitric oxide might just give older women wanting to become mothers a new, extended opportunity to do that.2 Researchers from Wayne State University in Detroit found that the substance appears to slow or reverse the aging of eggs, at least in mice ovaries. The finding suggests that nitric oxide could, one day, be used to help women in their 30s and 40s remain fertile longer, and increase their chances of having healthy babies, the scientists stated.
"Eggs from older women may be particularly sensitive to aging after they are released from the ovaries," said Husam Abu-Soud, PhD, an associate professor of Obstetrics, Gynecology, and Biochemistry at Wayne State, and the study's co-author. "As a result, the time available for optimal fertilization of these women's eggs may be quite a bit shorter than the timeframe in younger women."
The study was a collaboration between two laboratories at Wayne State University, Abu-Soud told Priority Healthcare, in an interview. Abu-Soud's lab has been studying molecular mechanisms related to nitric oxide for more than a decade. The second lab "has been primarily concerned with the effects of metabolic derangement on [egg] maturation and pre-implantation embryo development since the late 1980s," he said.
"This collaboration, therefore, combines the talents of two well-established research groups," said Abu-Soud.
Testing Nitric Oxide's Effects
For their research, the scientists gathered more than 1,500 eggs from mice ovaries one to two hours or four to six hours after ovulation. Mouse eggs that are not fertilized within hours of ovulation begin to age rapidly. After about six hours, these eggs are less likely to be fertilized properly, leading to chromosomal abnormalities in embryos if and when fertilization does occur.
But Abu-Soud and his team wanted to try to circumvent this expedited aging process by exposing the eggs to varying concentrations of nitric oxide. In older eggs, the substance appeared to slow the hardening of the eggs' outer walls, and increased the release of cortical granules, the molecules responsible for preventing more than one sperm from entering an egg during fertilization, both of which are signs of aging. Other signs of egg aging were delayed.
Other Roles of Nitric Oxide
Nitric oxide is a substance in the body produced by endothelial cells, which are those that line the interior of blood vessels. It helps relax the smooth muscle that lines the interior of blood vessels. As a result, blood vessels widen and help blood flow more easily. This is why inhaled nitric oxide is used as a therapy for some hypertensive-related diseases, such as pulmonary arterial hypertension.3
However, nitric oxide is also a "vital component" of egg development in the follicle, right through embryo development, the study researchers wrote. It also may be involved in the processes that determine egg quality and embryonic development potential. The form of nitric oxide used in this study was not the same as the inhaled gas, but "the idea is the same," explained Abu-Soud.
In addition to possibly extending fertility in older women, the study's findings suggest that nitric oxide could also help prevent the chromosomal abnormalities that may erupt in embryos, potentially causing Down syndrome, spontaneous miscarriages, and other pregnancy-related problems later, Abu-Soud's group stressed.
Theories Behind Its Prophylactic Effect
Why nitric oxide helps delay the aging of eggs, as seen in this study, is unknown, Abu-Soud told Priority Healthcare. "Although it is unclear how nitric oxide produced these results, we theorize that the compound may prevent irregularities in calcium release within the eggs," he explained. These abnormalities have been known to play a role in the aging of eggs in mammals.4
The results also increase the possibility that nitric oxide could be used to enhance the fertility of eggs retrieved for use in IVF procedures, Abu-Soud and his colleagues noted.
"Control of the processes of [egg] maturation and aging is particularly critical in modern techniques of assisted reproduction (ART)," they wrote. "… Matured [eggs], for instance, are typically utilized for in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and nuclear transfer. Postmaturation aging significantly affects the results of these procedures. Therefore, controlling [egg] aging could have many rewards in ART."
Up next, Abu-Soud and his colleagues plan to study the mechanisms that underlie nitric oxide's control over egg aging. This will likely lead to more research in animals, "as well as consideration of the application in humans, both as part of IVF/ET [embryo transfer] cycles, and … as part of spontaneous or stimulated cycles," Abu-Soud said.
1. Nasseri A, Grifo JA. Genetics, age, and infertility. Maturitas 1998 Oct 12;30(2):189-92.
2. Goud AP, Goud PT, Diamond MP, Abu-Soud HM. Nitric oxide delays oocyte aging. Biochemistry 2005 Aug 30;44(34):11361-8.
3. Beers MH, Berkow R, Bogin RM et al. Persistent pulmonary hypertension of the newborn. Treatment. In: The Merck Manual. 17th ed. Merck Research Laboratories: Whitehouse Station, NJ;1999:2143.
4. Igarashi H, Takahashi E, Hiroi M, Doi K. Aging-related changes in calcium oscillations in fertilized mouse oocytes. Mol Reprod Dev 1997 Nov;48(3):383-90.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications. John is a member of the American Medical Writers Association (AMWA).
