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Eur J Obstet Gynecol Reprod Biol ; 246: 60-66, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31962257


BACKGROUND: Maturity of the autonomic nervous system (ANS) is of paramount importance for fetal adaptation to extrauterine life and for early neurological development. Markers of ANS maturity, such as electrophysiological heart rate parameters, are of interest as tools to determine prenatal fetal maturity. The available technology, fetal magnetocardiography is expensive and not suitable for clinical use. Detection of fetal electrocardiographic signals using traditional ECG leads on the maternal abdomen may be brought to the bedside, but is technically challenging. Our group has recently developed an innovative system consisting of a standard ECG with external leads applied on the maternal abdomen coupled with a software that extracts the fetal heart signal from the maternal noise. OBJECTIVE: To validate the use of this innovative non-invasive system to detect fetal ECG (fECG) and its ability to detect changes in electrophysiological fetal cardiac parameters associated with ANS maturation. STUDY DESIGN: we recruited 50 pregnant women between 24 and 41 weeks and they received non-invasive recording of fECG. RESULTS: fECG was measurable at all gestational ages. Fetal heart rate variability (RR interval) and other associated parameters, such as low and high frequency increased with gestational age, particularly up to the 31st week. CONCLUSIONS: This study shows that non-invasive fECG is feasible throughout a broad range of gestational ages and allows detecting electrophysiological parameters of the fetal heart that may be used a surrogate of ANS maturity. Technological implementation of this system and its further exploitation may generate new tool to estimate fetal maturity.

Maturitas ; 99: 1-9, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28364860


BACKGROUND: Estetrol (E4) is a natural estrogen produced solely during human pregnancy. E4 is suitable for clinical use since it acts as a selective estrogen receptor modulator. In clinical trials E4 has been seen to have little or no effect on coagulation. Hence, it is interesting to investigate whether E4 alters endothelial-dependent fibrinolysis. OBJECTIVES: We studied the effects of E4 on the fibrinolytic system and whether this could influence the ability of endothelial cells to migrate. In addition, we compared the effects of E4 with those of 17ß-estradiol (E2). STUDY DESIGN: Human umbilical vein endothelial cells (HUVEC) were obtained from healthy women. Expression of plasminogen-activator inhibitor-1 (PAI-1), urokinase-type plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) proteins was evaluated by Western blot analysis. Endothelial cell migration was studied by razor-scrape horizontal and multiwell insert systems assays. RESULTS: E4 increased the expression of t-PA, u-PA and PAI-1 in HUVEC, but less so than did equimolar amounts of E2. The effects of E4 on t-PA, u-PA and PAI-1 were mediated by the induction of the early-immediate genes c-Jun and c-Fos. E4 in combination with E2 antagonized the effects induced by pregnancy-like E2 concentrations but did not impair the effects of postmenopausal-like E2 levels. We also found that the increased synthesis of PAI-1, u-PA and t-PA induced by E2 and E4 is important for horizontal and three-dimensional migration of HUVEC. CONCLUSIONS: These results support the hypothesis that E4 acts as an endogenous selective estrogen receptor modulator (SERM), controlling the fibrinolytic system and endothelial cell migration.

Movimento Celular/efeitos dos fármacos , Estetrol/farmacologia , Fibrinólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Ativador de Plasminogênio Tecidual/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/efeitos dos fármacos , Western Blotting , Células Cultivadas , Células Endoteliais , Endotélio Vascular/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo