Dysregulation of hydrogen sulphide metabolism impairs oviductal transport of embryos

Abstract

Embryo retention in the fallopian tube is thought to lead to ectopic pregnancy, which is a significant cause of morbidity. Hydrogen sulphide (H 2 S) is a gaseotransmitter produced mainly by cystathionine-g-lyase and cystathionine-b-synthase. Here we show that cystathionine-g-lyase and cystathionine -b-synthase are ubiquitously distributed in human fallopian tube epithelium and that H 2 S signalling relaxes the spontaneous contraction of the human oviduct. Furthermore, an aberration in H 2 S signalling, either silenced or enhanced activity induced by pharmacologic or genetic methods, causes embryo retention and developmental delay in the mouse oviduct, which is partly reversed by administration of either GYY4137, a slow-releasing H 2 S donor, or NaHS. Our findings reveal a new regulatory mechanism for oviductal embryo transport.

Oviduct: roles in fertilization and early embryo development

“…H 2 S is abundant in the Fallopian tube epithelial cells and synthesized intrinsically through the cell cytoplasm. This signaling pathway is upregulated during pregnancy and is mainly responsible for spontaneous oviduct muscle contraction, which provides a positive factor to the embryo movement toward the uterus (Ning et al 2014). Nitric oxide has been identified in the Fallopian tube; it mediates tubal muscle contraction, with possible roles in the regulation of sperm motility (Ekerhovd et al 1997, Kobayashi et al 2016.…”

Reduced Expression of Hydrogen Sulfide–Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor

“…Thus, the effect of other products of CSE and CBS on PGDH expression cannot be excluded. Interestingly, Ning et al 33 recently showed that CBS and CSE have a differential role in oviductal embryo transport, although the hydrogen sulfide donor shows the regulatory effect on oviduct contraction.…”

GYY4137, a Novel Water-Soluble, H2S-Releasing Molecule

“…Roles for H 2 S in female reproductive biology have only recently come to light. For example, both CBS and CSE are expressed in human intrauterine tissues and placenta (Patel, Vatish, Heptinstall, Wang, & Carson, 2009;You et al, 2011) as well as in epithelial cells of the fallopian tubes (Ning et al, 2014). The first direct evidence suggesting a role for H 2 S in reproductive biology was in preeclampsia, a hypertensive condition that affects around 4% of all pregnancies.…”

“…Interestingly, egg retention within the fallopian tube is associated with ectopic pregnancy and deregulation of fallopian tube contractility may play a part in this process. Indeed, disruption of H 2 S signaling has recently been reported to promote embryo retention and cause developmental delay in the mouse whilst pharmacological treatment with either GYY4137 or NaHS reversed these effects and restored the status quo (Ning et al, 2014).…”