The overall research goal in my laboratory is to understand ovarian physiology, with key emphasis on elucidating the cellular and molecular mechanisms involved in the periovulatory process of the expansion of cumulus oocyte complex (COC), ovulation, and CL formation in the ovary. The periovulatory process is prerequisite for successful fertility in females. Considerable research efforts have been directed to identify the factors that play crucial roles in these periovulatory processes, thus aiming to develop novel clinical approaches to improve female fertility or manage infertility-associated disorders.
The preovulatory gonadotropin (LH/FSH) surge induces the extensive reprogramming of gene expression in periovulatory follicles to bring out the periovulatory process. Transcription factors induced by the LH surge in the periovulatory follicles play a central role in these processes by directly controlling the expression of periovulatory genes. Of particular interest in our laboratory has been on a family of transcription factors, Core Binding Factor (CBF/PEBP2/RUNX). CBF is a heterodimeric transcription factor composed of α and β subunits: the α subunit is encoded by one of three Runx genes (Runx1, Runx2, and Runx3) and β subunit is encoded by a single gene, CBFβ. We have recently reported that Runx1 and Runx2 expression is highly up-regulated by the LH surge in periovulatory follicles and the up-regulation of Runx1/2 is important for the regulation of periovulatory genes. One of ongoing projects in our laboratory is to determine the specific actions of CBF in periovulatory follicular cells and it functional significance in the ovulatory process and cumulus expansion using in vivo and in vitro models. Further studies aims to identify and define the actions of LH-induced/activated transcriptional regulatory machinery that controls the periovulatory process.
Other projects in the laboratory involve deciphering the regulatory mechanisms involved in steroidogenic shift and progesterone metabolism during the periovulatory period. Recently, we have reported “Prostate Androgen Regulated Protein 1 (PARP1)” as a novel regulator of progesterone metabolism in luteinizing granulosa cells in rats. The expression of this protein is also highly up-regulated in periovulatory follicles and this up-regulation is critical for progesterone accumulation. Progesterone is a key regulator of reproductive events, including ovulation, luteinization and pregnancy. In addition, P4 serves as a precursor of other steroids (e.g., sex steroids and corticoids) which control a wild range of physiological processes from reproduction to stress and immune responses. Therefore, the identification of novel mechanism(s) regulating progesterone production and metabolism will greatly improve our understanding of steroidogenesis and tissue specific regulation of steroids.
Liu J, Park ES, Jo M. (2009) Runt-related transcription factor 1 regulates luteinized hormone-induced prostaglandin-endoperoxide synthase 2 expression in rat periovulatory granulosa cells.Endocrinology. Jul;150(7):3291-300.
Li F, Liu J, Park E-S, Jo M, Curry TE Jr. (2009) The B Cell Translocation Gene (BTG) Family in the Rat Ovary: Hormonal Induction, Regulation, and Impact on Cell Cycle Kinetics. Molecular Endocrinology 150:3894-3902.
Bridges, P.J., Jo M, Al Alem L., Na G., Su W., Gong M.C. and Ko C. (2010). Production andbinding of endothelin-2 (EDN2) in the rat ovary at ovulation: Endothelin receptor subtype A(EDNRA) mediated contraction. Reproduction, Fertility and Development 22:780-787.
Park ES, Lind AK, Dahm-Kähler P, Brännström M, Carletti MZ, Christenson LK, Curry TE Jr, Jo M. (2010) RUNX2 transcription factor regulates gene expression in luteinizing granulosa cells of rat ovaries. Mol Endocrinol.24(4):846-58.
Li F, Liu J, Jo M, Curry TE Jr. (2011) A role for nuclear factor interleukin-3 (NFIL3), a critical transcriptional repressor, in down-regulation of periovulatory gene expression. Molecular Endocrinology 25:445-59.
Bridges PJ, Jeong M, Shim S, Park JY, Lee JE, Sapsford LA, Trudgen K, Ko C, Gye MC, and Jo M.(2012)Hematopoetic prostaglandin D synthase: an ESR1-dependent regulator of inflammatory gene expression in the mouse oviduct. Endocrinology. Apr;153(4):1925-35
Park ES, and Jo M. (2012) A role for RUNX2 as a transcriptional repressor in periovulatory granulosa cells. Mol Cell Endocrinol. Oct 15;362(1-2):165-75
Li F, Jang H, Jo M, Curry TE Jr. (2012) Ovarian FAM110C (family with sequence similarity 110C): Induction during the periovulatory period and regulation of granulosa cell cycle kinetics. Biology of Reproduction 86(6):185.
Li F, Jo M, Curry TE Jr , Liu J. (2012) Hormonal induction of polo-like kinases (Plks) and impact of Plk2 on cell cycle progression in the rat ovary PLoS One. 2012;7(8):e41844