Expression And Function Of Endogenous H₂S Signaling System In Human Oviduct Tissue

IntroductionHydrogen sulide (H2S) is now considered the third member of the gaseotransmitter family, has been implicated in several physiological and pathophysiological processes. H2S is generated from L-cysteine mainly by cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS). H2S is an endogenous signaling molecule that appears to regulate vascular and airway smooth muscle cell contraction. The tubal exhibits both phasic and tonic contractile activity. However, the existence of H2S signal system in oviduct tissue is also unknown. If there is, it would not affect the movement of oviduct and the transportation of oviductal embryo. In the present study, we investigate the expression, localization and function of endogenous H2S in the rat、mice and human fallopian tube. In order to find a new signaling molecules regulate the movement of oviduct, and we can provide a new idea about the tubal pregnancy mechanism.Materials and MethodsHuman fallopian tubes were obtained from salpingectomy for ectopic pregnancy, postpartum hemorrhage hysterectomy, postpartum sterilization and ovarian cancer. Wistar rats and BALB/c mice were from the Animal Center of Shandong University School of Medicine. In the study, Western blots (human oviduct tissue was homogenized and separated on SDS-PAGE), immunofluorescence (paraffin sections were used), strips detection and H2S release test were used. Furthermore, we also investigated the embryo transportation by count embryos, which in oviduct and uterus involve BALB/c mice, wild-type (WT) and CBS+/-mice. Professor Yi Fan (Department of Pharmacology, School of Medicine, Shandong University) gifted CBS+/-mice.ResultsIn our present study, we firstly show that the CBS and CSE are ubiquitously distributed in human fallopian tube epithelium by immunofluorescence and Western blot, and expression was significantly increased tubal pregnancy. Determination of H2S in tissue further confirmed tubal tissue can synthesize and release H2S, fallopian tubal pregnancy tissue content higher H2S than normal group of patients. Experimental in vitro tissue tension shows that endogenous and exogenous H2S signaling mediates the spontaneous contraction of human oviduct. Pharmacology and CBS+/-mice in vivo studies, we verified that oviductal embryo transport was mediated by endogenous H2S. Furthermore, an aberration H2S, either silenced or enhanced by pharmacologic or genetic methods, causes embryo retention. Importantly, exogenous H2S can be significantly reduced the inhibition of endogenous H2S-caused embryo retention in mice. In addition, an aberration H2S also causes embryo development during early pregnancy.ConclusionCollectively, the results suggest that endogenous H2S signaling system is exist in fallopian tube and regulates the spontaneous contraction of oviduct. If the H2S signaling system is abnormalities or disorders, oviductal embryo transport and early embryo development are delayed. In conclusion, our findings reveal a new regulatory mechanism for oviductal embryo transport, which could be potential new target for treating or preventing ectopic pregnancy.