Unlocking Preeclampsia Solutions: Investigating G Protein-Coupled Estrogen Receptor Activation In Preeclampsia

Unlocking Preeclampsia Solutions: Investigating G Protein-Coupled Estrogen Receptor Activation In Preeclampsia

Characterization of Pelvic Organ Prolapse

Spectral photoacousti imaging measuring placental oxygenation in two models of preeclamptic rats.

Activation of GPER by G-1 increases placental oxygenation in vivo in two different models of preeclampsia in rats. Spectral photoacoustic imaging measures of placental oxygenation show the impaired placental function induced by the RUPP surgical procedure and in preeclamptic Dahl S rats in comparison with normal pregnant animals. Treatment with G-1 at 100 μg/kg/day significantly increased oxygen saturation in pregnant both RUPP and Dahl S rats compared to untreated rats. Data is presented as mean ± SEM (n = 2-4).

Preeclampsia poses a significant threat to maternal and fetal well-being, demanding innovative therapeutic solutions. Current anti-hypertensive therapies are ineffective and carry teratogenic risks to the babies, highlighting the need for novel approaches. The G protein-coupled estrogen receptor (GPER) shows promise due to its crucial role in placental development and cardiovascular function. In our preliminary studies using the reduced uterine perfusion pressure (RUPP) preeclamptic rat model, selective GPER stimulation with its agonist G-1 demonstrated positive outcomes and a safe fetal profile. While the RUPP rat serves as an acute model of preeclampsia, the Dahl Salt Sensitive (Dahl S) model allows for a temporal investigation across early and late stages of pregnancy. We aim to characterize the physiological changes induced by the clinical GPER agonist LNS8801, a purified chemical agonist of G-1 currently in clinical trials for solid tumors, in preeclamptic Dahl S rats. In conclusion, our research proposing the investigation of GPER’s in vivo impact using the clinical agonist LNS8801 in Dahl S animals addresses a critical gap and offer personalized interventions for pregnant individuals facing preeclampsia.

References

Lawrence DJ, Bayer CL. Photoacoustic imaging provides an in vivo assessment of the preeclamptic placenta remodeling and function in response to therapy. Placenta. 2022 Aug;126:46-53.

[DOI]

Alencar AKN, Swan KF, Pridjian G, Lindsey SH, Bayer CL. Connecting G protein-coupled estrogen receptor biomolecular mechanisms with the pathophysiology of preeclampsia: a review. Reprod Biol Endocrinol. 2023 Jul 1;21(1):60.

[DOI]