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.