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October 18, 2012

Contact: Steven Benowitz steven.benowitz@tuhs.temple.edu


Keith Latham, PhDLooking at the expression of hundreds of genes before and after ovulation, researchers at Temple University School of Medicine have uncovered new insights into the complex interplay of cells that help nurture the development of the unfertilized egg. They have discovered that one type of cell actually can revert to another type, perhaps at the request of the egg, and provide the developing egg with needed hormones and other factors.


The researchers say that a better understanding of such interactions and their effects on egg development will help them to determine factors that can potentially improve egg quality, and perhaps lead to the identification of biological markers that can predict quality as well. Their results, reported recently in the journal Endocrinology, may have implications for improving in vitro fertilization techniques in humans and livestock.


“The quality of eggs is important in making decisions in assisted reproduction settings, such as in vitro fertilization,” noted senior author Keith Latham, PhD, Professor of Biochemistry at Temple University School of Medicine and a member of the Fels Institute for Cancer Research and Molecular Biology. “We’re trying not only to better understand what determines egg quality, but also find ways – new markers – that will help us gauge and predict quality non-invasively.”


Dr. Latham and his team are interested in improving and determining the quality of oocytes, or immature eggs, and improving outcomes in assisted reproduction in humans and livestock.


In assisted reproduction, oocyte maturation is stimulated artificially, and these oocytes can be screened based on size, shape and various other characteristics, explained Dr. Latham. “We’d like to be able to isolate and choose the best quality oocyte, fertilize and implant it and achieve a healthy delivery, but it is frequently difficult to be able to know which are always the most viable and most likely to result in successful pregnancies.”


Gene Expression in Supportive Cells Lends Insight to Egg Development


According to Dr. Latham, because the oocyte is surrounded by cumulus cells, which support its development, looking at gene expression in the cumulus cells can potentially mirror the quality of the oocyte. He and his co-workers previously reported 24 potential gene markers of oocyte quality expressed in cumulus cells.


In the current study, he and his team analyzed gene expression in non-human primate ovary cells, examining another supportive cell, the granulosa cell, which is not directly connected to the oocyte, but influences its development inside the egg follicle. The researchers looked at how granulosa cells change before and after ovulation, and compared them to what was happening in the cumulus cells during oocyte maturation.


“We were surprised to see that during maturation and ovulation, the cumulus cells became more granulosa cell-like in their gene expression characteristics,” he said. “It was surprising because previous thinking in follicle development was that cumulus cells arise from an early population of granulosa cells, and these cumulus cells are recruited by the oocyte by this early population to become more specialized. Our data suggest it’s not a one-way path. As the egg is being ovulated, the cumulus cells are reverting back to a granulosa cell-like state.”


Dr. Latham said that as cumulus cells become specialized, they physically touch the oocyte, and begin a complex dialogue that fosters oocyte growth and maturation. Ovulation breaks the physical contact, the oocyte’s role in maintaining the cumulus cell is interrupted, and the cumulus cell can revert back to an earlier state.


“The granulosa cells normally supply hormone factors supporting high quality oocyte development. What may be happening is at ovulation, the cumulus cell-oocyte complex is removed from the follicle, forming this environment where granulosa cells can provide certain useful factors. Cumulus cells are reverting back and taking over the granulosa cells’ role and providing beneficial effects. That’s a potential exciting avenue to explore.”


Exploiting the Cell-Switch Factor


Dr. Latham thinks this cumulus-granulosa cell switch can be exploited. “If there are factors that granulosa cells and subsequently cumulus cells are providing to support high quality oocyte growth, it might be possible to provide those factors directly to the oocyte to enhance assisted reproduction,” he said. “Instead of being limited to just picking the best oocyte, maybe we can enhance the quality of all oocytes. If we could provide some factors to these oocytes that make them of higher quality, it may be useful for patients who have a history of multiple rounds of unsuccessful attempts at assisted reproduction.”


Other researchers who contributed to this research include Charles L. Chaffin, University of Maryland; Young S. Lee, Bela G. Patel, Temple University School of Medicine; and Catherine A. VandeVoort, California National Primate Research Center and the University of California, Davis.


The research was supported by grants from the National Institutes of Health.