Extracellular matrix influences hormone and protein production by human chorionic villi

Abstract

Increasing evidence confirms that the extracellular matrix greatly influences cell behaviour and function. Collagen and fibrin are in contact with trophoblast throughout pregnancy. To investigate whether these two matrices influence hormone production by the trophoblast, explants from first-trimester chorionic villi were cultured for up to 30 days either a) in medium with agitation, b) embedded in type-I collagen (three-dimensional gels), or c) embedded in fibrin (three-dimensional gels). The supernatant culture medium was changed every 48 h and tested by radioimmunoassay for hCG, progesterone and pregnancy-associated plasma protein A. In addition, after 3, 7, 15, and 30 days of culture villi were fixed and studied by light and electron microscopy. Embedding in the extracellular matrix showed higher and longer-lasting production rates of all measured products and superior structural preservation as compared to cultures with agitation. Collagen matrix proved to be superior to fibrin. As established by several tests, this difference was neither due to thrombin used to polymerize fibrinogen, nor to differences in the diffusion rates through the two different matrices used. We conclude that extracellular matrix, particularly collagen, influences the synthesis of trophoblastic products. Embedding of the villous explants in three-dimensional gels constitutes a new method for long-term cultures of chorionic villi.

Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta

“…Continuous fusion of the villous cytotrophoblast with the syncytiotrophoblast is not only the basis for growth of the syncytiotrophoblast but also a prerequisite to keep the latter alive (for review see Benirschke and Kaufmann 1995); loss of the villous cytotrophoblast or absence of syncytial fusion results in degeneration of the syncytiotrophoblast within a few days, as demonstrated by in vitro and animal experiments (Fox 1970;Panigel and Myers 1972;Castellucci et al 1990). However, the reasons why continuous incorporation of the cytotrophoblast is needed for syncytial survival remain obscure, as are the events which promote syncytial death.…”

“…Most syncytial "sprouts" in the human placenta are not due to true villous sprouting (Cantle et al 1987;Castellucci et al 1990), rather they result from the accumulation of aged nuclei (Martin and Spicer 1973;Jones and Fox 1977;Cantle et al 1987; for review see Benirschke and Kaufmann 1995) prior to extrusion into the maternal circulation. Syncytial nuclei demonstrating advanced features of apoptosis were mostly confined to these structures (Figs.…”

Syncytial fusion of human trophoblast depends on caspase 8

“…12 The approach described here focuses on caspase 8 protein expression and caspase 8 protein activities in an in vitro model using villous explants. In this model, villous cytotrophoblast continues to proliferate and structural organization of the villous trophoblast layer stays intact for several days, 32,33 even in the presence of antisense oligonucleotides. 34 The explant model allows the observation of cytotrophoblast fusion in the living complex placental tissue.…”

Peripheral Reproductive Organ Health and Melatonin: Ready for Prime Time

“…The villous cytotrophoblasts, on the other hand, continue to proliferate, differentiate and fuse to form a syncytium, the multinucleated syncytiotrophoblast [136]. This syncytial tissue is non-proliferative and rapidly undergoes apoptosis [137]. The development and transformation of villous cytotrophoblasts make them reminiscent of tumor cells [138] and they have actually been referred to as having pseudo-tumorigenic properties [139].…”