The objectives of this study were to evaluate the effects of a nitric oxide (NO) donor on embryo development in vitro and on implantation of embryos in vivo in mice. Mouse embryos (2-cell) were incubated in media containing different concentrations of diethylenetriamine/NO (DETA/NO), a nitric oxide donor, and development was monitored daily for 4 days. Specificity of NO effects was assessed by using DETA without NO or 48 h preincubated DETA/NO. In in-vivo studies, mated mice were continuously infused, subcutaneously, with various concentrations of DETA/NO or DETA through mini-osmotic pumps (from day 1 of pregnancy), and implantations in the uterus were assessed on day 6. None of the embryos progressed beyond 4-cell stage when exposed to 0.1 or 1.0 mM DETA/NO compared with 94.5% of control embryos that developed beyond the morula stage by day 4. Embryo development was unaffected by lower (0.001 and 0.01 mM) concentrations of DETA/NO, 48 h preincubated DETA/NO, or DETA only. Infusion of DETA/NO to mice caused inhibition of embryo implantation in a dose-dependent manner. No implantation sites were observed in mice infused with a daily dose of 20 micromol DETA/NO rate, compared with an implantation rate of 81.8% in control or DETA-treated mice. This study demonstrates for the first time that higher concentrations of NO inhibit both embryo development in vitro and implantation in vivo in mice.
Objective: To review the literature and synthesize evidence on pathophysiological interactions attributed to the simultaneous occurrence of COVID-19 and preeclampsia.
Methods: A systematic review was conducted from November (2021) to January (2022) to retrieve observational studies published on the PubMed, LILACS, SciELO Brazil and Google Scholar databases. The search was based on the descriptors [(eclampsia OR preeclampsia) AND (COVID-19)]. Quantitative studies that pointed to pathophysiological interactions were included. Literature reviews, studies with HIV participants, or with clinical approach only were excluded. The selection of studies was standardized and the evaluation was performed by pairs of researchers.
Results: In this review, 155 publications were retrieved; 16 met the inclusion criteria. In summary, the physiological expression of angiotensin-converting enzyme-2 (ACE-2) receptors is physiologically increased in pregnant women, especially at the placental site. Studies suggest that the coronavirus binds to ACE-2 to enter the human cell, causing deregulation of the renin-angiotensin-aldosterone system and in the ratio between angiotensin-II and angiotensin-1-7, inducing manifestations suggestive of preeclampsia. Furthermore, the cytokine storm leads to endothelial dysfunction, vasculopathy and thrombus formation, also present in preeclampsia.
Conclusion: The studies retrieved in this review suggest that there is a possible overlap of pathophysiological interactions between COVID-19 and preeclampsia, which mainly involve ACE-2 and endothelial dysfunction. Given that preeclampsia courses with progressive clinical and laboratory alterations, a highly quality prenatal care may be able to detect specific clinical and laboratory parameters to differentiate a true preeclampsia superimposed by covid-19, as well as cases with hypertensive manifestations resulting from viral infection.
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