Implantation failure and inadequate placental development are important contributors to infertility, recurrent miscarriage, and other pregnancy-related problems in women. Better understanding of these processes is hampered by the difficulty in obtaining human tissue from which primary cells can be prepared and by the very limited access worldwide to human blastocysts for experimentation. Therefore, the use of appropriate cell lines, particularly for functional studies of implantation and placentation, is imperative. While a number of cell lines for both endometrium and trophoblast have been developed and are widely used, it is difficult for researchers to decide which of these are most appropriate for studies of particular functions. This brief review summarizes the known phenotypes of the most widely used cell lines and indicates which might be the most appropriate for individual studies.
This review provides the basis for an evidence-based approach towards changes in routine IVF, which may ultimately result in higher delivery rates of healthier term babies.
Human endometrium possesses a unique immunological environment enabling implantation of the semiallogeneic embryo. Large populations of macrophages and uterine-specific natural killer cells infiltrate the implantation site, believed to be important modulators of trophoblast invasion and decidualization. In the absence of pregnancy, there is a dramatic influx of neutrophils, eosinophils, and macrophages, likely to be critical for focal inflammatory endometrial destruction. However, little is known regarding selective recruitment of leukocyte subtypes. We employed a gene array approach to analyze the expression of 21 chemokines in endometrium. Real-time RT-PCR and immunohistochemistry was conducted to verify expression patterns and determine cellular source. Nine chemokines were highly abundant in human endometrium: monocyte chemotactic protein-3, eotaxin, fractalkine, macrophage inflammatory protein-1beta, 6Ckine, IL-8, hemofiltrate CC chemokine-1 and -4, and macrophage-derived chemokine. Chemokine mRNA was generally up-regulated during endometrial receptivity and early pregnancy, particularly of macrophage and natural killer chemoattractants. Chemokine protein was predominantly localized to epithelial glands, whereas differentiated stromal cells were a major source of chemokines after decidualization. This is the first study to use an unbiased approach to screen for endometrial chemokines, and we report the selective regulation of chemokines, corresponding to the recruitment of distinct leukocyte subpopulations required for pregnancy and menstruation.
Metformin reduced soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from primary human tissues, possibly by inhibiting the mitochondrial electron transport chain. The activity of the mitochondrial electron transport chain was increased in preterm preeclamptic placenta. Metformin reduced endothelial dysfunction, enhanced vasodilation in omental arteries, and induced angiogenesis. Metformin has potential to prevent or treat preeclampsia.
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