John Eppig, Ph.D.

Professor Emeritus

Dr. John Eppig is a Professor Emeritus at The Jackson Laboratory in Bar Harbor, Maine. His research focused on the development and function of the mammalian oocyte-granulosa cell complex. He achieved the first complete development of mammalian oocytes in vitro. This included in vitro initiation of primordial follicle development, oocyte growth, and acquisition of competence to undergo maturation, fertilization, and, after transfer of preimplantation embryos to foster mothers, the birth of live young. He originated the concept of an oocyte-granulosa cell regulatory loop in which bi-directional communication between the oocyte and companion granulosa cells is essential for both normal oocyte and follicular development. A major goal of his current research is to define the components of this regulatory loop and their mechanism(s) of action. He is the Principal Investigator of a Program Project to develop mouse mutant models of infertility using ENU mutagenesis. In this Program, he uncovered a gene named meiosis arrest female 1 (Marf1) that is master gene essential for controlling meiosis and protecting genomic integrity from assault by retrotransposons in oocytes. He was awarded the Gregor Mendel Honorary Medial of Merit in Biological Sciences by the Academy of Sciences of the Czech Republic in 2002, Chaired the Gordon Conference on Mammalian Gametogenesis and Embryogenesis in 1998, was President of the Society for the Study of Reproduction in 1999-2000, and became Co-Editor-in-Chief of Biology of Reproduction in July 2004. He received the Research Award in 1999 and the Carl G. Hartman Award in 2010 from the Society fro the Study of Reproduction. Dr. Eppig was elected as a member to the National Academy of Sciences in 2011 and currently serves on the Editorial Board of PNAS.

Selected References

Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ.  2010.  Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes.  Science. 330:366-369.

Sugiura K, Su YQ, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ.  2010.  Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15.  Mol Endocrinol. 24:2303-2314.

Bolcun-Filas E, Bannister LA, Barash A, Schimenti KJ, Hartford SA, Eppig JJ, Handel MA, Shen L, Schimenti JC.  2011.  A-MYB (MYBL1) transcription factor is a master regulator of male meiosis.  Development 138:3319-3330.

Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ. 1011.  Estradiol promotes and maintains cumulus cell expression of Natriuretic Peptide Receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro.  Endocrinology 152(11):4377-4385.

Su YQ, Sugiura K, Sun F, Pendola JK, Cox GA, Handel MA, Schimenti JC, Eppig JJ. 2012. MARF1 regulates essential oogenic processes in mice. Science 23;335(6075):1496-1499.

Robinson JW, Zhang M, Shuhaibar LC, Norris RP, Geerts A, Wunder F, Eppig JJ, Potter LR, Jaffe LA. 2012. Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes. Dev Biol 366:308-316.

Su YQ, Sun F, Handel MA, Schimenti JC, and Eppig JJ. 2012. Meiosis arrest female 1 (MARF1) has nuage-like function in mammalian oocytes. Proc Nat Acad Sci (USA) 109:18653-18660.

Peng J, Li Q, Wigglesworth K, Rangarajan A, Kattamuri C, Peterson RT, Eppig JJ, Thompson TB, Matzuk MM. 2013. Growth differentiation factor 9:bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc Natl Acad Sci U S A. 110(8):E776-785.

Dokshin GA, Baltus AE, Eppig JJ, Page DC, 2013. Oocyte differentiation is genetically dissociable from meiosis in mice. Nature Genetics 45: 877-883.

Emori C, Wigglesworth L, Fujii W, Naito K, Eppig JJ, Sugiura K, 2013. Cooperative effects of 17beta-estradiol and oocyte-derived paracrine factors on the transcriptome of mouse cumulus cells. Endocrinology 154: 4859-4871.

Wigglesworth K, Lee KB, O'Brien MJ, Peng J, Matzuk MM, Eppig JJ, 2013. Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes. Proc Nat Acad Sci U S A 110: E3723-3729.

Handel MA, Eppig JJ, Schimenti JC. 2014. Applying "gold standards" to in-vitro-derived germ cells. Cell. 5:157(6):1257-61. doi: 10.1016/j.cell.2014.05.019. Erratum in: Cell. 2014 Sep 25:159(1):216.

Peng J, Wigglesworth K, Rangarajan A, Eppig JJ, Thompson TB, Matzuk MM. 2014. Amino  acid 72 of mouse and human GDF9 mature domain is responsible for altered homodimer bioactivities but has subtle effects on GDF9:BMP15 heterodimer activities. Biol Reprod. 91(6):142.

Wigglesworth K, Lee KB, Emori C, Sugiura K, Eppig JJ. 2015. Transcriptomic diversification of developing cumulus and mural granulosa cells in mouse ovarian  follicles. Biol Reprod. 92(1):23.

Pattabiraman S, Baumann C, Guisado D, Eppig JJ, Schimenti JC, De La Fuente R.  2015.  Mouse BRWD1 is critical for spermatid postmeiotic transcription and female meiotic chromosome stability.  J Cell Biol. 208:53-69.  PMCID: PMC4284233.

Mandal M, Hamel KM, Maienschein-Cline M, Tanaka A, Teng G, Tuteja JH, Bunker JJ, Bahroos N, Eppig JJ, Schatz DG, Clark MR.  2015.  Histone reader BRWD1 targets and restricts recombination to the lgk locus.  Nat. Immunol.  PMCID: PMC4575638.

Guo J, Shi L, Gong X, Jiang M, Yin Y, Zhang X, Yin H, Li H, Emori C, Sugiura K, Eppig JJ, Su YQ.  2016.  Oocyte-dependent activation of MTOR in cumulus cells controls the development and survival of cumulus-oocyte complexes.  J Cell Sci.  129:3091-3103.   PMCID: PMC5004896.