Expression of Cystathionine [beta]-synthase and Cystathionine [gamma]-lyase in Human Pregnant Myometrium and Their Roles in the Control of Uterine Contractility

• Published in: PloS one Vol. 6; no. 8; p. e23788
• Main Authors: You, Xing-Ji, Xu, Chen, Lu, Jian-Qiang, Zhu, Xiao-Yan, Gao, Lu, Cui, Xiao-Rui, Li, Yuan, Gu, Hang, Ni, Xin
• Format: Journal Article
• Language: English
• Published: Public Library of Science 23-08-2011
• Subjects: Analysis; Cysteine; Cystine; Hydrogen sulfide; Immunohistochemistry; Ligases; Pregnancy; Pregnant women; RNA
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023788

Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H.sub.2 S) has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H.sub.2 S produced locally in the control of uterine contractility during labour is unknown. Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-[gamma]-lyase (CSE) and cystathionine-[beta]-synthetase (CBS), the principle enzymes responsible for H.sub.2 S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H.sub.2 S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10.sup.-7 -10.sup.-2 mol/L), a precursor of H.sub.2 S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10.sup.-3 mol/L) increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K.sub.ATP) channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips. H.sub.2 S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H.sub.2 S synthetic enzymes is down-regulated during labour, suggesting that H.sub.2 S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.