Expression of the clock genes Per1 and Bmal1 during follicle development in the rat ovary. Effects of gonadotropin stimulation and hypophysectomy

Sep 4, 2012Cell and tissue research

Daily gene activity during egg follicle growth in rat ovaries and how hormone signals and pituitary removal affect it

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Abstract

The expression of clock genes Per1 and Bmal1 is low and arrhythmic during early follicle development in prepubertal and hypophysectomised rats.

Clock gene expression becomes rhythmic in ovarian cells following stimulation with equine chorionic gonadotropin (eCG).
Rhythmic clock gene expression is also observed in the granulosa cells of preovulatory follicles after additional stimulation with human chorionic gonadotropin (hCG).
Findings suggest that the initiation of clock gene rhythms in the rat ovary is linked to luteinising hormone receptor activity.
In hypophysectomised rats, rhythmic clock gene expression occurs in the corpora lutea and secondary interstitial cells, indicating gonadotropin-independent regulation.

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Daily oscillations of clock genes have recently been demonstrated in the ovaries of several species. Clock gene knockout or mutant mice demonstrate a variety of reproductive defects. Accumulating evidence suggests that these rhythms act to synchronise the expression of specific ovarian genes to hypothalamo-pituitary signals and that they are regulated by one or both of the gonadotropins. The aim of this study has been to examine the spatio-temporal expression of the clock genes Per1 and Bmal1 during gonadotropin-independent and gonadotropin-dependent follicle development in the rat ovary. We have examined the ovaries of prepubertal rats, of prepubertal rats stimulated with equine chorionic gonadotropin (eCG)/human chorionic gonadotropin (hCG) and of hypophysectomised adult animals. Using quantitative reverse transcription with the polymerase chain reaction, in situ hybridisation histochemistry and immunohistochemistry, we have demonstrated that the expression of the two clock genes is low and arrhythmic in ovarian cells during early gonadotropin-independent follicle development in prepubertal animals and in hypophysectomised animals. We have also demonstrated that the expression of the clock genes becomes rhythmic following eCG stimulation in the theca interna cells and the secondary interstitial cells and that, following additional hCG stimulation, the expression of the clock genes also becomes rhythmic in the granulosa cells of preovulatory follicles. These findings link the initiation of clock gene rhythms in the rat ovary to the luteinising hormone receptor and suggest a functional link to androgen and progesterone production. In hypophysectomised animals, rhythmic clock gene expression is also observed in the corpora lutea and in secondary interstitial cells demonstrating that, in these compartments, entrainment of clock gene rhythms is gonadotropin-independent.

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Expression of the clock genes Per1 and Bmal1 during follicle development in the rat ovary. Effects of gonadotropin stimulation and hypophysectomy

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