JAX Notes December 01, 2008

Dr. John Eppig honored for research in reproductive science

Jackson Laboratory Professor John Eppig, Ph.D., widely acknowledged as a pioneer in reproductive biology, was honored with the 2007 Pioneer in Reproduction Research Lectureship Award from the Frontiers in Reproduction Research Program. The award, recognizing Dr. Eppig as an outstanding reproductive biologist and reflecting the esteem of his peers, was bestowed at a ceremony at the Marine Biological Laboratory in Woods Hole, Mass.

"It's incredibly exciting and gratifying to know your colleagues in the field of reproductive biology think highly enough of you to give you an award. It's really a thrill," said Dr. Eppig.

Dr. Eppig joined The Jackson Laboratory in 1975 and has focused on reproductive biology ever since. He is probably best known for being the first to successfully produce live offspring from primordial oocytes developed completely in vitro (Eppig et al. 1996). He has also been researching how the oocyte-cumulus cell complex matures. One facet of this research has involved determining how the oocyte-derived members of the TGFb superfamily, particularly growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), regulate follicular function and ovulation. Eppig and his laboratory found that, to compensate for their metabolic deficiencies, mammalian oocytes promote metabolic pathways in cumulus cells. In analyzing the transcriptomes of cumulus cells from wild-type, Bmp15-deficient, and Bmp15-/- Gdf9+/- double mutant mice, he found the following:

  • Most of the genes encoding enzymes for sterol biosynthesis are down-regulated in the mutant cumulus cells and in wild-type cells whose oocytes are removed;
  • Little newly synthesized cholesterol is present in these cumulus cells;
  • Many genes that encode enzymes in the cholesterol biosynthetic pathway are robustly expressed in wild-type cumulus cells but hardly expressed in wild-type oocytes; and
  • Newly synthesized cholesterol is significantly higher in cumulus-enclosed oocytes than in denuded oocytes.

He concluded that oocytes obtain cholesterol (which they cannot make) from cumulus cells after providing them with cholesterol synthesis-promoting BMP15 and GDF9 (Sugiura et al. 2007, 2005; Diaz et al. 2006; Eppig et al. 2005).

In another facet of his quest to understand how the oocyte-cumulus cell complex matures, Dr. Eppig has been studying how preantral granulosa cells become cumulus cells during the preantral to antral follicle transition. So far, he has discovered that: 1) growing oocytes in the preantral follicle do not secrete enough of the factors that enable transformation, and 2) the granulosa cells in the preantral follicle do not yet have the ability to respond to these factors and to EGF (Diaz et al. 2006).

Dr. Eppig has also been instrumental in establishing and directing The Jackson Laboratory Reproductive Genomics Program (reprogenomics.jax.org), the goal of which is to produce, characterize and map new mouse models of infertility and make them available to the wider scientific community (JAX® NOTES 2007).

References

(Author in bold is a Jackson Laboratory scientist.)

Diaz FJ, Wigglesworth K, Eppig JJ. 2007. Oocytes are required for the preantral granulosa cell to cumulus cell transition in mice. Dev Biol 305:300-11.

Diaz FJ, OÕBrien MJ, Wigglesworth K, Eppig JJ. 2006. The preantral granulose cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion. Dev Biol 299:91-104.

Eppig JJ, Pendola FL, Wigglesworth K, Pendola JK. 2005. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod 73:351-7.

Eppig JJ, OÕBrien MJ. 1996. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod 54:197-207.

JAX¨ NOTES. 2007. The Jackson Laboratory Reproductive Genomics Program. JAX¨ NOTES 507:7.

Sugiura K, Su YQ, Diaz FJ, Pangas SA, Sharma S, Wigglesworth K, OÕBrien MJ, Matzuk MM, Shimasaki S, Eppig JJ. 2007. Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134:2593-603.

Sugiura K, Eppig JJ. 2005. Society for Reproductive Biology Founders Lecture 2005. Control of metabolic cooperativity between oocytes and their companion granulose cells by mouse oocytes. Reprod Fertil Dev 17:667-74