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The role of the H2S and OT systems in pre-eclampsia

Merz, T.; Ecker, S.; Denoix, N.; McCook, O.; Kranz, S.; Wachter, U.; Rottler, E.; Papadopoulos, T.; Fusch, C.; Brucker, C.; Triebel, J.; Bertsch, T.; Radermacher, P.; Waller, C.

2025-06-09 obstetrics and gynecology
10.1101/2025.06.06.25329101 medRxiv
Show abstract

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H2S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, liked to their anti-oxidant and hypotensive effects. Thus, the role of the interaction of the OT and H2S systems in the context of PE was further elucidated in the present clinical case control study "NU-HOPE" (Nurnberg-Ulm: The role of H2S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesarztekammer Bayern, file number 19033, 29th August 2019), comparing uncomplicated pregnancies, early-onset PE (ePE, onset <34 weeks gestational age) and late-onset PE (lPE, onset >34 weeks gestational age). Routine clinical data, serum H2S and homocysteine levels, tissue protein expression as well as nitrotyrosine formation were determined. The main findings were (i) unchanged plasma sulfide levels (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H2S enzymes and OT receptor in the placenta in lPE, (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H2S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection.

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