Control of ovulation in mice by progesterone receptor-regulated gene networks.
The mid-cycle surge of luteinizing hormone (LH) induces ovulation, a process during which a fertilizable oocyte is released from a mature ovarian follicle. Although ovulation is a physiologically well-characterized event, the underlying molecular pathways remain poorly understood. Progesterone receptor (PGR), which mediates the biological effects of the steroid hormone progesterone, has emerged as a key regulator of ovulation in mice. The development of a progesterone-receptor-null (Pgr-null) mouse model confirmed a critical role of this hormone in ovulation because in these mutant mice, mature pre-ovulatory follicles fail to release the oocytes. This animal model has thus presented a unique opportunity to study the molecular pathways underlying ovulation. Gene-expression profiling experiments by several groups, using the ovaries of Pgr-null mice, revealed novel gene networks, which act downstream of PGR to control ovulation. These genes encode diverse molecules such as proteases, transcription factors, cell-adhesion molecules, modulators of vascular activities and regulators of inflammation. Functional analyses using gene-knockout mouse models have confirmed that some of these factors play critical roles during ovulation. The knowledge gained from these studies has helped us to understand better the molecular mechanisms that facilitate the release of oocytes from pre-ovulatory follicles. Further analysis of the role of molecular regulators of ovulation will help identify useful molecular targets that would allow the development of improved contraceptives and new therapeutics for anovulatory infertility.
Kim
Jaeyeon
J
Department of Molecular and Integrative Physiology, Center for Research in Reproduction and Infertility, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Bagchi
Indrani C
IC
Bagchi
Milan K
MK
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D006080:Ovarian Follicle / Q000378:metabolism; D010060:Ovulation / Q000502:physiology*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D011980:Receptors, Progesterone; D007986:Luteinizing Hormone