鞘氨醇代谢通路在早期胚胎转运和发育及输卵管妊娠发生中的作用

Sphingosine 1-phosphate (S1P), a product of sphingomyelin metabolism, is generated via phosphorylation of sphingosine by sphingosine kinases(SphKs). It acts via a family of G protein-coupled receptors or as an intracellular second messenger for agonists acting through the S1P receptors (S1P1-5). Our preliminary data show that SphK1 and S1P1 were localized in human fallopian tube epithelium, and this signalling pathway involved in the regulation of oviduct spontaneous contraction. Our in vivo experiment further suggest that sphingosine 1-phosphate metabolism in oviduct regulates oviductal embryo transport and early embryo development. Intrugingly, we found that an aberration of sphingosine 1-phosphate metabolism existed in ectopic pregnancy. So we hypothesize that sphingosine 1-phosphate metabolic pathway involves in early embryo transport, development and oviductal pregnancy. To test this hypothsis, we plan to investigate (1) whether sphingosine 1-phosphate metabolic pathway regulates early embryo transport, (2) embryo development by either silenced or enhanced pharmacologic or genetic methods,(3) an aberration of this signalling pathway involves in oviductal pregnancy. Our studies will reveal a new regulatory mechanism for oviductal embryo transport, which could be potential new target for treating or preventing ectopic pregnancy.

1-磷酸鞘氨醇（Sphingosine 1-phosphate，S1P）由鞘氨醇激酶（sphingosine kinases，SphKs）催化鞘氨醇而产生。最近我们发现人输卵管组织存在内源性SphKs/S1P代谢通路，且参与输卵管平滑肌舒缩活动的调节, 进一步研究发现在输卵管妊娠时输卵管S1P聚集浓度下降，妊娠小鼠给予S1P出现早期胚胎滞留及发育迟缓，提示输卵管脂质代谢可能参与早期胚胎在输卵管的转运及发育。为验证该假设，我们采用SphK1-/+基因缺陷小鼠和转基因及药理学的方法研究（1）鞘氨醇代谢通路是否参与早期胚胎在输卵管中的转运；（2）鞘氨醇代谢通路是否调节胚胎的早期发育；（3）鞘氨醇代谢的异常是否可导致胚胎转运滞留和发育迟缓。研究将首次揭示输卵管鞘氨醇代谢通路调节早期胚胎在输卵管的转运及发育，该研究将为进一步探讨输卵管妊娠的发生机理和新的治疗靶点提供依据。