Circadian Clock Gene Plays a Key Role on Ovarian Cycle and Spontaneous Abortion

Sep 22, 2015Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

Circadian clock gene is important for the ovarian cycle and natural miscarriage

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Abstract

Abnormal expression of CLOCK in fetuses is associated with spontaneous miscarriage.

CLOCK expression peaks at the 6th week in healthy mouse fetuses.
Knockdown of the CLOCK gene in mouse embryonic stem cells induces cell death and inhibits cell growth.
In vivo experiments show that CLOCK knockdown results in fewer released oocytes and smaller litter sizes compared to controls.
Findings suggest that CLOCK is important for female fertility and may increase the risk of miscarriage when disrupted.

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BACKGROUND/AIMS: Circadian locomotor output cycles protein kaput (CLOCK) plays a key role in maintaining circadian rhythms and activation of downstream elements. However, its function on human female reproductive system remains unknown.

METHODS: To investigate the potential role of CLOCK, CLOCK-shRNAs were transfected into mouse 129 ES cells or injected into the ovaries of adult female mice. Western blotting was utilized to analyze the protein interactions and flow cytometry was used to assess apoptosis.

RESULTS: The expression of CLOCK peaked at the 6th week in the healthy fetuses. However, an abnormal expression of CLOCK was detected in fetuses from spontaneous miscarriage. To determine the effect of CLOCK on female fertility, a small hairpin RNA (shRNA) strategy was used to specifically knockdown the CLOCK gene expression in vitro and in vivo. Knockdown of CLOCK induced apoptosis in mouse embryonic stem (mES) cells and inhibited the proliferation in mES cells in vitro. CLOCK knockdown also led to decreased release of oocytes and smaller litter size compared with control in vivo.

CONCLUSIONS: Collectively, theses findings indicate that CLOCK plays an important role in fertility and that the CLOCK knockdown leads to reduction in reproduction and increased miscarriage risk.

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Circadian Clock Gene Plays a Key Role on Ovarian Cycle and Spontaneous Abortion

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