MiR-200b and miR-429 Function in Mouse Ovulation and Are Essential for Female Fertility

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Science  05 Jul 2013:
Vol. 341, Issue 6141, pp. 71-73
DOI: 10.1126/science.1237999

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Female Infertility

Anovulation, the failure of a woman's ovary to release an oocyte, is a major cause of female infertility. The mechanisms of ovulation have been studied extensively, with the hypothalamicpituitary axis serving as a key player in its regulation. Hasuwa et al. (p. 71, published online 13 June) describe a mechanism by which anovulation can be caused by the disruption of two microRNAs that are expressed in the pituitary gland.


Ovulation in the mouse and other mammals is controlled by hormones secreted by the hypothalamo-pituitary-ovarian axis. We describe anovulation and infertility in female mice lacking the microRNAs miR-200b and miR-429. Both miRNAs are strongly expressed in the pituitary gland, where they suppress expression of the transcriptional repressor ZEB1. Eliminating these miRNAs, in turn, inhibits luteinizing hormone (LH) synthesis by repressing transcription of its β-subunit gene, which leads to lowered serum LH concentration, an impaired LH surge, and failure to ovulate. Our results reveal roles for miR-200b and miR-429, and their target the Zeb1 gene, in the regulation of mammalian reproduction. Thus, the hypothalamo-pituitary-ovarian axis was shown to require miR-200b and miR-429 to support ovulation.

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