A molecule believed to play a role in embryo implantation in the uterus at the earliest stage of pregnancy may have strong implications for infertility in women, according to an international team of scientists. The researchers uncovered the molecule—known as lysophosphatidic acid, or LPA—in a group of mice, and published their findings in the journal Nature earlier this month.1
"Every successful pregnancy requires proper embryo implantation," wrote Jerold Chun, MD, PhD, a professor of Molecular Biology at Scripps Research Institute in La Jolla, California, and his fellow scientists in their study paper. "Low implantation rate is a major problem during infertility treatments using assisted reproductive technologies. Here, we report a newly discovered molecular influence on implantation …"
Implantation Implications in Infertility
In cases where unexplained infertility remains unresolved, experts have theorized that problems with embryo implantation may be one significant factor. Normally, implantation takes place about five to eight days after fertilization. The embryo attaches to the uterine lining, typically near the top. Implantation is completed by day 9 or 10 after fertilization.2
When a cause for infertility can't be determined, doctors will typically order further tests to determine if such a cause can be found. Some of these tests may include an analysis of body temperature and ovulation, an x-ray of the fallopian tubes and uterus, and diagnostic laparoscopy, a type of minimally invasive surgery. For men, initial tests focus on semen analysis.3
Infertility at the Molecular Level
The LPA molecule is a receptor on the surfaces of cells that make up the uterus. Receptors are molecules that, when activated, cause the cells to take some sort of action. In female reproduction, when the LPA receptor is activated, implantation occurs because the endometrium (uterine tissue) becomes more receptive (biologically speaking) to the embryo arriving from the fallopian tube. Without this receptivity, implantation fails.
In fact, there are nine types of LPA receptors in all. Over the last decade, Chun's group has been studying the effects of removing one or more of these receptors in mice, he told Priority Healthcare. But scientists in other studies determined that LPA1 and LPA2 didn't have any apparent effect on female reproductive function. So, Chun's team bred mice that lacked LPA3 and then observed the resulting effect on implantation and pregnancy in the animals.
Negative Effects After Removing LPA3
They found that while ovulation and embryo development were unaffected by the lack of LPA3, embryo implantation and subsequent pregnancy were delayed compared to mice that had the receptor. This, in turn, resulted in delayed embryonic development and embryo death, in some cases. Embryo positioning in the uterus was also abnormally crowded, and significantly fewer litters later resulted in the animals lacking this apparently vital molecule, Chun's group found.
The investigators also learned that levels of prostaglandins, a fatty acid essential for implantation, were also much lower in these mice. When the researchers gave the mice doses of synthetic prostaglandins, they discovered that implantation was subsequently successful. "This intervention was conducted for experimental rather than therapeutic reasons," Chun explained. "Whether this type of intervention could hold therapeutic potential is speculative at this point in time."
Will the Same Hold True in People?
One caveat of this finding is that results shown in mice aren't always reproducible in humans. But Chen and his group are hopeful. They say that if such a molecule plays the same key role in embryo implantation in women, this could be a new target for infertility therapy with the aim of boosting implantation success. "This raises the possibility of creating medicines that influence implantation timing, a critical factor for in vitro fertilization, and also for reducing the incidence of multi-embryo gestations …" they wrote.
1. Ye X ,Hama K, Contos JJ et al. LPA3-mediated lysophosphatidic acid signaling in embryo implantation and spacing. Nature 2005 May 5;435(7038):104-8.
2. The Merck Manual. Stages of Development. Available at: http://www.merck.com/mmhe/sec22/ch257/ch257c.html?qt=embryo%20implantation&alt=sh. Accessed May 24, 2005.
3. American Society for Reproductive Medicine (ASRM). Frequently Asked Questions About Infertility. Available at: http://www.asrm.org/Patients/faqs.html#Q3:. Accessed May 24, 2005.
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.
