Circadian clocks are all but ubiquitous in nature. Circadian rhythms, those biological rhythms with a period at or near 24h, are found in most, if not all, physiological systems ranging from cellular physiology and biochemistry to whole animal physiology. The mechanism controlling these oscillations is a now well-understood molecular oscillator composed of an autoregulatory transcriptional-translational feedback loop. This loop consists of interacting "clock gene" transcriptional regulators that facilitate precision through an elegant temporal scheme of positive and negative gene expression.
Our lab and others have recently determined that the circadian clock mechanism is present in the cells of the ovarian follicle. Further, we have determined that the ovary maintains an "endogenous" pattern of sensitivity to gonadotrophins that does not appear to be dependent on the timing of the LH surge or a fully developed endocrine and neuroendocrine system. These data, together with the data from other labs, suggests that the ovarian clock may play a substantial role in the timing of events in the ovary, related to both the ovulatory response to gonadotrophins and the timing of steroidogenesis.
The Sellix laboratory is currently focused on two distinct but interrelated facets of this research by asking two fundamental questions:
1) Does "clock-controlled" gene expression in the ovary, more specifically the various ovarian cell types, play a substantial role in the timing of ovarian physiology and more specifically the timing of ovulation and/or steroid hormone biosynthesis
2) Do disease states that negatively impact reproductive function (e.g. PCOS, etc.) do so by altering the timing of clock gene or clock-controlled genes in the tissues of the hypothalamo-pituitary-ovarian axis? Further, is phase-synchrony among these oscillators (or lack thereof) a contributing factor to the onset and progression of disease?