With implications for infertility, researchers report that human eggs have been produced from stem cells. The research is published in the latest issue of the journal Reproductive Biology and Endocrinology.1
Doctors at the University of Tennessee say their work could eventually be significant for people who are infertile or become prematurely menopausal.
It's the first study to show that human eggs can be derived from the cells on the surface of ovaries, explained Antonin Bukvosky, MD, PhD, DSc, in an interview with Priority Healthcare. Bukovsky is a professor of Obstetrics and Gynecology at the University of Tennessee, and is editor-in-chief of the journal in which this study was published.
Evolving Research
A decade ago, Bukvosky and his fellow researchers reported about their discovery that female germ cells—the cells that make up the reproductive system—are found on the surfaces of the ovaries.2 Now, this study is an extension of that.
"Ten years ago, we have shown that [ovarian surface] cells in adult human ovaries can differentiate into new germ cells," he said. "Last year, we have shown that these germ cells migrate into deeper layers of the adult human ovary, mature into [eggs] and associate with primitive granulosa cells [those that line the walls of follicles], to form new primary follicles."
For the latest in-vitro study, the researchers collected cells from the surfaces of ovaries, and maintained them in culture. Some of the cells were maintained in an estrogen medium known as phenol red used to stimulate their growth, and the rest were not, as a comparison. Those held in the estrogen medium eventually developed into human eggs. The ovarian cells had been taken from a group of women aged 39 to 52 for the study.
This research was based not only on previous animal studies that found eggs could be derived from embryonic stem cells collected from mice and maintained in-vitro,3 but also previous studies on the differentiation of stem cells.2,4
Adult stem cells are those found in a tissue or organ that can renew themselves and can also differentiate; that is, transform into the major specialized cell types of the respective tissue or organ in which they are found. The major roles of adult stem cells are to maintain and repair the tissue in which they reside. Similarly, embryonic stem cells—those found in embryos—are primitive cells that have the potential to become a wide variety of specialized cell types.5 This study involved ovarian stem cells.
Infertility Implications
The eggs that resulted were suitable for fertilization and embryo development, Bukovsky's group noted.
"Development of numerous mature oocytes [eggs] from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility," wrote Bukovsky and his associates. There is at least one potential clinical application for growing human eggs from ovarian stem cells, the investigators pointed out, such as a future therapy for women diagnosed with premature ovarian failure due to the absence of follicles in their ovaries.
The technique is relatively easy and could be performed by laparoscopy, a type of minimally invasive abdominal surgery, and could yield additional cells for use in IVF.
"There are, however, additional studies required to make sure that these new eggs are suitable for use in clinical applications," Bukovsky told Priority Healthcare. "We are attempting to expand our existing studies in several ways."
For example, researchers want to know if ovarian stem cells can still produce eggs after being frozen for any length of time, whether there are differences in the ability to produce eggs in vitro involving women with premature menopause, and whether one method for deriving eggs from ovarian stem cells is better than another, he said.
Other Clinical Possibilities
In addition to a potential treatment for infertility, the findings of this study point to the possibility that frozen ovarian stem cells from younger females could be frozen to produce fresh eggs later. "This may prevent the occurrence of fetal genetic alterations, which are often associated with pregnancies in advanced maternal age, possibly due to the lack of follicular renewal in aging ovaries," the research team wrote.
This technique may also be therapeutic for women at risk of developing premature menopause by providing a new round of primary follicles for them, resulting "in a 10-to-12 year delay of the onset of natural menopause," Bukovsky and his team wrote.
"Thanks to the broad interest of the public and the prestigious fertility specialists, we believe there will be a global effort to test possible clinical applications of our observations," Bukovsky said.
1. Bukovsky A, Svetlikova M, Caudle MR. Oogenesis in cultures derived from adult human ovaries. Reprod Biol Endocrinol 2005 May 5;3(1):17. [Epub ahead of print].
2. Bukovsky A, Keenan JA, Caudle MR, Wimalasena J, Upadhyaya NB, Van Meter SE. Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis. Am J Reprod Immunol 1995 Apr;33(4):323-40.
3. Hubner K, Fuhrmann G, Christenson LK et al. Derivation of oocytes from mouse embryonic stem cells. Science 2003;300:1251-6.
4. Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol 2004;2:20.
5. National Institutes of Health (NIH). U.S. Department of Health and Human Services. Stem Cell Basics. Available at: http://stemcells.nih.gov/info/basics/basics4.asp. Accessed May 11, 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.
