Meiosis is the signature event of the germ cell developmental program, absolutely required for sexual reproduction eukaryotes. Proper regulation of meiotic progression is crucial for production of functional gametes. A key aspect of meiosis is a germ cell specific cell cycle, in which a final round of DNA synthesis (premeiotic S) is followed by a greatly extended G2, termed meiotic prophase, prior to the two meiotic divisions. This signature cell cycle delay provides critical time for homologous chromosomes to pair, synapse and recombine, as well as for major biosynthetic events that drive gamete differentiation. In oocytes, the transcriptional, translational and morphogenetic changes that produce the egg and prepare for early embryogenesis are largely accomplished during meiotic prophase. In male germ cells, although dramatic morphological changes that produce mature gametes occur after the meiotic divisions, a major part of the gene expression program that sets up spermiogenesis takes place during meiotic prophase. In both sexes, meiotic onset, progression, maturation, and activation of the meiotic divisions are key regulatory points. Understanding how these events are regulated is key for understanding the molecular basis of meiotic arrest infertility, for designing effective strategies for differentiating germ cells from embryonic precursors, and for developing and maturing competent gametes in vitro. The analysis proposed in this subproject of the U54 Cooperative Center for Reproductive and Stem Cell Biology will elucidate fundamental mechanisms that control the cell cycle for meiotic prophase, including the critical control circuits that first pause the cell cycle, then finally activate the G2/M transition for meiosis I once proper expression of the program for gametogenesis has been achieved.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-L)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
United States
Zip Code
Durruthy Durruthy, Jens; Ramathal, Cyril; Sukhwani, Meena et al. (2014) Fate of induced pluripotent stem cells following transplantation to murine seminiferous tubules. Hum Mol Genet 23:3071-84
Dominguez, Antonia A; Chiang, H Rosaria; Sukhwani, Meena et al. (2014) Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies. Sci Rep 4:6432
Ramathal, Cyril; Durruthy-Durruthy, Jens; Sukhwani, Meena et al. (2014) Fate of iPSCs derived from azoospermic and fertile men following xenotransplantation to murine seminiferous tubules. Cell Rep 7:1284-97
Durruthy-Durruthy, Jens; Briggs, Sharon F; Awe, Jason et al. (2014) Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions. PLoS One 9:e94231
Reddy, Pradeep; Deguchi, Masashi; Cheng, Yuan et al. (2013) Actin cytoskeleton regulates Hippo signaling. PLoS One 8:e73763
Pera, Renee A Reijo (2013) Status of human germ cell differentiation from pluripotent stem cells. Reprod Fertil Dev 25:396-404
Medrano, Jose V; Pera, Renee A Reijo; Simon, Carlos (2013) Germ cell differentiation from pluripotent cells. Semin Reprod Med 31:14-23
Kawamura, Kazuhiro; Cheng, Yuan; Suzuki, Nao et al. (2013) Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A 110:17474-9
Hsueh, Aaron J; Rauch, Rami (2012) Ovarian Kaleidoscope database: ten years and beyond. Biol Reprod 86:192
Cheng, Yuan; Kawamura, Kazuhiro; Deguchi, Masashi et al. (2012) Intraovarian thrombin and activated protein C signaling system regulates steroidogenesis during the periovulatory period. Mol Endocrinol 26:331-40

Showing the most recent 10 out of 11 publications