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Reproductive Sciences
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Contractility and Calcium Signaling of Human Myometrium Are Profoundly Affected by Cholesterol Manipulation: Implications for Labor?

Jie Zhang, MBBS

University of Liverpool

Annabelle Kendrick, MBBS

Liverpool Women's Hospital Liverpool, UK

Siobhan Quenby, MD

University of Liverpool

Susan Wray, PhD

University of Liverpool, s.wray{at}liv.ac.uk

The authors elucidate cholesterol's effect on human uterine contractility and calcium signaling to test the hypotheses that elevation of cholesterol decreases uterine activity and that oxytocin cannot augment contraction when cholesterol is elevated. The effects of cholesterol extraction with methyl ß-cyclodextrin and enrichment with low-density lipoproteins and cholesterol on contractile activity and intracellular calcium signaling in spontaneous or oxytocin-stimulated myometrium are determined. Force occurring spontaneously and with oxytocin is significantly increased by cholesterol extraction. Cholesterol enrichment profoundly inhibits force production in a dose-dependent manner and could reverse the effects of cholesterol extraction. Qualitatively similar results are found for nonpregnant and pregnant laboring and non-laboring myometrium. These contractile changes are related to changes in intracellular Ca2+ . Thus, elevated cholesterol is deleterious to contractility and Ca2+ signaling in human myometrium. Cholesterol may contribute to uterine quiescence but could cause difficulties in labor in obese/dyslipidemic women, consistent with their increased cesarean delivery rates

Key Words: Uterus • obesity • raft • caveolae • calcium • signaling • smooth muscle.

Reproductive Sciences, Vol. 14, No. 5, 456-466 (2007)
DOI: 10.1177/1933719107306229
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