RESUMEN
To systematically study the partition of environmental metals including lead, mercury, and cadmium and essential minerals such as iron, manganese, copper, and zinc in the maternal/fetal unit of healthy pregnant women, we analyzed blood and umbilical cord blood samples of 50 healthy mother/child pairs using a biomonitoring approach. The levels of essential minerals in healthy pregnant women were significantly different from those of the general population. The partition of essential minerals and environmental metals and their associations between maternal and umbilical cord blood were metal-specific. Lead entered the fetal environment nearly unaffected. The median fetal level was only 10 % lower than the corresponding maternal concentration (10.3 vs. 11.5 µg/l, P = 0.0038). Mercury accumulated in the fetal unit resulting in more than a threefold increase in fetal compared to maternal exposure (1.48 vs. 0.44 µg/l, P < 0.0001). In contrast, placental transfer of Cd was limited, and median fetal exposure was <0.1 µg/L. We finally used the data to assess the influence of exposures to environmental metals on fetal homeostasis of essential minerals because environmental metals such as lead are capable of interfering with normal cellular functions of essential minerals by mimicking their pathways. A subtle but systematic and dose-dependent effect of environmental exposure to lead on fetal homeostasis of manganese and iron in terms of reducing their concentrations in the fetal unit was found (P ≤ 0.039). The observed associations remained unaffected in the presence of mercury and cadmium. The results illustrate the need to establish specific normative levels of essential minerals in pregnant women. Additionally, the study provides initial insights into the mode-of-action of lead in the fetus at current environmental exposures.
Asunto(s)
Hierro/sangre , Manganeso/sangre , Intercambio Materno-Fetal , Metales Pesados/sangre , Adolescente , Adulto , Estudios Transversales , Exposición a Riesgos Ambientales/análisis , Femenino , Sangre Fetal/química , Humanos , Recién Nacido , Masculino , Embarazo , Adulto JovenRESUMEN
Progestins are successfully used in the treatment of endometriosis; however, the exact mechanisms of their action are still unsolved. We here focused on the effect of different progestins on parameters of extracellular matrix degradation and angiogenesis involved in the establishment and maintenance of ectopic endometrial lesions. Human endometrium was intraperitoneally transplanted into nude mice. After 7 and 28 days of treatment with progesterone, dydrogesterone, or its metabolite dihydrodydrogesterone, respectively, ectopic lesions were evaluated for proliferation and apoptosis. Expression of estrogen receptor alpha, progesterone receptor-AB, the angiogenetic factors, cysteine-rich angiogenic inducer (CYR61), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGFA) and the matrix metalloproteinase (MMP)-2, -3, -7 and -9 was investigated. Functional impact on angiogenesis was evaluated by density of microvessels and of vessels stabilized by pericytes within the ectopic lesions. Although dydrogesterone significantly reduced proliferation of endometrial stromal cells after 28 days, suppression of apoptosis was independent from progestins. Expression of MMP-2 was significantly reduced by all progestins and MMP-3 by dydrogesterone. In the grafted endometrial tissue, transcription of bFGF was suppressed by progesterone and dihydrodydrogesterone, and VEGFA and CYR61 by dihydrodydrogesterone and dydrogesterone. In parallel, microvessel density was slightly suppressed by progestins, whereas number of stabilized vessels increased. Thus, progestins regulate factors important for the establishment and maintenance of ectopic endometrial lesions.