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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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Abstract

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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Acknowledgments

The skillful technical assistance of Anita Hansen, Juliano Olsen and Yvonne Søndergaard is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Herlev Hospital, Faculty of Health Sciences, University of Copenhagen, 2730, Herlev, Denmark

    Søren Gräs

  2. Depatment of Clinical Biochemistry, Faculty of Health Sciences, Bispebjerg Hospital, University of Copenhagen, 2400, Copenhagen NV, Denmark

    Birgitte Georg, Henrik L. Jørgensen & Jan Fahrenkrug

Authors
  1. Søren Gräs
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  2. Birgitte Georg
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  3. Henrik L. Jørgensen
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  4. Jan Fahrenkrug
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Correspondence to Søren Gräs.

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This study was supported by a grant from the Danish Biotechnology Centre for Cellular Communication.

The authors have no conflict of interest to declare.

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Gräs, S., Georg, B., Jørgensen, H.L. et al. Expression of the clock genes Per1 and Bmal1 during follicle development in the rat ovary. Effects of gonadotropin stimulation and hypophysectomy. Cell Tissue Res 350, 539–548 (2012). https://doi.org/10.1007/s00441-012-1489-2

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  • DOI: https://doi.org/10.1007/s00441-012-1489-2

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