INTRODUCTION
Pre-eclampsia is defined as hypertension developing after 20 weeks’ gestation with one or more of the following: proteinuria, maternal organ dysfunction (including renal, hepatic, hematological, or neurological complications), or fetal growth restriction 1-3. The mechanisms involved in the onset of pre-eclampsia are still unclear, but may involve an abnormal placentation with subsequent release of antiangiogenic biomarkers, mediated primarily by soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng)4,5. Soluble sFlt-1 is an anti-angiogenic protein that binds to the functional receptor binding domain of vascular endothelial growth factor (VEGF), neutralizing the ability of VEGF to signal to endothelial cells lining arteriolar blood vessels to maintain vasorelaxation 4,5. These events are combined with suppression of the release of pro-angiogenic placental growth factor (PlGF), which further limits the promotion of development and maturation of the placental vascular system 1,4. Beside their anti-angiogenic effects, high levels of sFlt-1 and sEng combined to the suppression of PlGF, also result in endothelial dysfunction, vasoconstriction, and immune dysregulation, which can negatively impact every maternal organ system and the fetus 1-6.
Gaseous molecules such as nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have the potential to regulate placental blood through their roles in angiogenesis, cytoprotection and regulation of vascular tone 6-10. Abnormal vascular tone and endothelial dysfunction in pre-eclampsia are attributed to the reduction of NO and H2S bioavailability, which are key vasodilator regulators in placenta 5-7. Researchers have showed that activation of heme oxygenase-1 (HO-1)/carbon monoxide (CO) as well as H2S/cystathionine-γ-lyase system can suppress sFlt-1 and sEng release and prevent placental stress in experimental models 7. Placental production of H2S, expression of H2S-producing enzymes (i.e., cystathionine beta-synthase and cystathionine-γ-lyase), and plasma H2S concentrations are all reduced in human pregnancies complicated by preeclampsia 5-7. Interestingly, the potential of H2S as a mechanism-based therapy for preeclampsia has been successfully tested with several H2S donors in preclinical studies 11.
Since 2016, repetitive and massive strandings of sargassum seaweed have occurred along Caribbean coasts resulting in H2S emission, which comes from the natural decomposition of sargassum in the absence of oxygen 12-14. Depending on H2S levels, clinical characteristics of H2S exposure range from mucosal irritation (10-50 ppm) to pulmonary edema, coma and cardiopulmonary arrest (> 500 ppm) 15-18. While the effects elicited by acute exposure are reasonably well documented, less is known about the deleterious effects of H2S exposure over longer periods19. Long-term exposure to H2S levels in industrial and geothermal areas have previously shown increased morbidity for respiratory diseases and disorders of the central nervous system, whereas others studies found no evidence of an association20-29. In the specific context of sargassum strandings, we have previously reported associations between day-to-day variations in H2S levels and disorders of the central nervous, respiratory system, and small intestine in subjects living in the most intensely impacted coastlines with the highest ambient H2S levels 13.
Regarding the cardiovascular impact of chronic H2S exposure, the few epidemiological studies carried out evaluating the relationship between H2S and cardiovascular diseases are inconclusive 20,26,27. Evidence of both protective role and deleterious effects of H2S in cardiovascular diseases, including hypertension, has been demonstrated30-32. Whether increased ambient H2S levels due to sargassum strandings may alter the incidence of preeclampsia in pregnant women is unknown. The main objective of the present study was to determine whether H2S exposure due to anaerobic decomposition of sargassum strandings was associated to occurrence of preeclampsia in Martinique, a French Oversea Caribbean Island.