Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation.
Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Lili
L
Sheibani
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Thomas J
TJ
Lechuga
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Honghai
H
Zhang
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Afshan
A
Hameed
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Deborah A
DA
Wing
Department of Obstetrics and Gynecology, University of Texas Medical Branch-Galveston, Galveston, Texas, USA.
Sathish
S
Kumar
Department of Pediatrics and Obstetrics and Gynecology, University of Texas Southwestern Medical School, Dallas, Texas, USA.
Charles R
CR
Rosenfeld
Department of Obstetrics and Gynecology, University of California Irvine, Irvine, California, USA.
Dong-Bao
DB
Chen
D000328:Adult; D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism*; D055988:Uterine Artery / Q000378:metabolism*; D014664:Vasodilation
D004967:Estrogens; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
cystathionine-beta-synthase; hydrogen sulfide; pregnancy; uterine vasodilation; women