Rhythmic expression of clock and clock-controlled genes in the rat oviduct

Abstract

The rhythmic expression of clock and clock-controlled genes in the rat oviduct was investigated by real time RT-PCR. per1, per2, Clock, Bmal1, cry1 and cry2 were all expressed in the oviduct. With 4-hourly sampling over 24 h in a normal photoperiod, analysis of variance indicated that per2 and Bmal1 had highly significant sinusoidal-like changes with an amplitude of 3- and 10-fold respectively. Of the other clock genes, per1 and cry1 had non-significant rhythm amplitudes of 2.5- and 1.8-fold respectively. Using the same experimental approach the rhythmic expression of Bmal1, per1 and per2 mRNA in the liver was found to be highly significant with amplitudes of approximately 20-, 10- and 5-fold respectively. The expression of the clock-controlled transcription factors DBP and Rev-erb alpha showed significant rhythmicity in the oviduct with 5-fold changes in amplitude for both genes. Plasminogen activator inhibitor-1 (PAI-1), which has been implicated in oviduct function during the preimplantation period, also had a significant rhythm of expression (2.5-fold amplitude), peaking at the same time as the other clock-controlled genes, DBP and Rev-erb alpha. These results show for the first time that the female reproductive tract is inherently rhythmic and suggests that the developing embryo may be subjected to rhythmic changes in the environment created by the oviduct during transition to the uterus.

Circadian rhythms and fertility

“…The first studies on animals with genetically altered 6 rhythmicity were conducted on Clock mutant mice (Vitaterna et al, 1994) which produce a 7 truncated CLOCK protein which is capable of dimerising with its partner BMAL1, but not 8 bind to the regulatory E-box sequences in the promoters of Per1, Per2, Cry1, Cry2 and other 9 genes (King et al, 1997). The Clock mutant mice kept in a 12L:12D photoperiod generally 10 confine their activity to the dark period (ie., are entrained) (Kennaway et al, 2003; Vitaterna 11 et al, 1994) and sustain rhythmicity, albeit with a very long period of approximately 27 12 hours, for at least a few cycles in continuous darkness. Moreover they can actually be 13 entrained to a skeleton photoperiod (0.5L:23.5D) suggesting that light dependent entrainment 14 mechanisms are retained (Kennaway et al, 2003).…”

“…The Clock mutant mice kept in a 12L:12D photoperiod generally 10 confine their activity to the dark period (ie., are entrained) (Kennaway et al, 2003; Vitaterna 11 et al, 1994) and sustain rhythmicity, albeit with a very long period of approximately 27 12 hours, for at least a few cycles in continuous darkness. Moreover they can actually be 13 entrained to a skeleton photoperiod (0.5L:23.5D) suggesting that light dependent entrainment 14 mechanisms are retained (Kennaway et al, 2003). When maintained on a CBA background 15 which has the capacity to synthesise melatonin, the Clock mutants rhythmically secretes this They produce normal amounts of estradiol and progesterone and undergo normal follicular 2 development and corpora lutea formation following ovulation.…”

Meal Time Shift Disturbs Circadian Rhythmicity Along with Metabolic and Behavioral Alterations in Mice

“…These molecular rhythms have also been found in peripheral organs including female reproductive tissues such as the ovary [64,65], uterus [66][67][68], and oviducts [69] (Figure 1).…”

Biological rhythms and fertility: the hypothalamus–pituitary–ovary axis

“…On the contrary, the circadian expression of Per1 is only transiently detectable in decidual tissue, in light/dark conditions only. 58 The first evidence for the expression of clock genes in the oviduct was also provided by Johnson et al, 59 and fur ther supported by Kennaway et al, 19 who investigated the rhythmic expression of clock and clockcontrolled genes in the rat oviduct via 4hour samples collected over a 24hour period. In addition to the rhythmic expression of clock genes, they found significant rhythmicity in the expression of clockcontrolled genes, such as D site of albumin promoter (albumin Dbox) binding protein, Reverbα, and plasmi nogen activator inhibitor1, suggesting that the embryo is exposed to a circadian rhythmicity, which may be crucial in the early stages of implantation and development.…”

“…3,19,62 In detail, Clock/ Clock mutant mice were found with prolonged irregular estrous cycles, which are characterized by shorter proestrus but longer estrous compared with wildtype or Clock /+ females. 62 The authors did not find any ovarian anomalies, eg, normal estrogen or progesterone levels on diestrus and proestrus and the development of normal ovarian cells.…”