The teratogenicity and behavioral teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) in a chick model.

Inhibitory effects of nephrotoxic antisera on the growth of rat fetuses

Prior to 1927, when Brunschwig proposed that the rat visceral yolk sac is functionally a placenta, it was customary to consider the chorio-allantoic placenta as the primary organ for bringing nourishment to and taking waste from the developing embryo and growing fetus. Eight years later, Everett (1935) predicted that the visceral yolk sac is functionally at least as important as the chorio-allantoic placenta, while Noer & Mossman (1947) suggested that the yolk sac functions differently from the placenta and is therefore complementary in its role. More recently, Halliday (1955) indicated that the proximal yolk sac of the rat is capable of absorbing antibodies by day 17 of gestation. This was confirmed by Brambell & Halliday (1956), who were able to demonstrate that the vitelline epithelium and its underlying vascular system are partly responsible for antibodies penetrating into the embryo. Padykula, Deren & Wilson (1966) noted that the rat yolk sac has the ability to absorb vitamin B 12 and that this ability is stimulated by the presence of intrinsic factor. The yolk sac has also been shown to be capable of actively transporting certain amino acids (Deren, Padykula & Wilson, 1966) and is able to accumulate ferritin by means of pinocytosis (Lambson, 1966). In addition to being a physiologically dynamic organ, the yolk sac also undergoes biochemical changes during gestation. Padykula (1958) and Johnson & Spinuzzi (1966, 1968) have demonstrated that the activities of a variety of histochemically and electrophoretically distinguishable enzymes in the yolk sac change with increasing gestational age. In addition, the latter investigators have been able to show that the repertory of multiple molecular forms of certain enzymes is altered in the presence of a potent teratogenic agent. Since most investigations of mammalian placental function have been limited to studies in late fetal or term placentae, the fact that the rat visceral yolk sac also serves a placental function affords the opportunity to study the relationships and exchange mechanisms operating between the embryo and a placental organ

Effects of trypan blue and Niagara blue 2 B on the in vitro absorption of ions by the rat visceral yolk sac

During the past several years there has been a marked increase of interest in, and attention to, reproductive and developmental toxicology. Knowledge that reproductive capacity and embryonic development can be altered by environmental and other factors is not new though it has expanded considerably, perhaps due in part to increased public awareness and expanded research efforts. Coupled with this awareness is the fact that women are entering the workplace at an increasing rate and in a wider variety of settings. In contemporary society the fact of pregnancy does not necessarily preclude gainful employment any more than it has ever precluded the considerable work of the homemaker. Taken together, these factors tend to focus attention on considerations of reproductive effects. All parties are aware that both the primary and secondary organs of reproduction maybe vulnerable to the toxic action of specific agents just as may any other organ or organ system.

A review of advances in prescreening for teratogenic hazards

Using the rodent embryo culture techniques of New (1978), it can be demonstrated that, over the 48-hours culture period, the in-vitro growth and development, of explanted 9.5 days old post-implan­ tation rat conceptuses, in immediately-centrifuged and heat-inactivated homologous serum is almost indistinguishable from that which occurs in-vivo op-to 11.5 days. Moreover, using these methods, it has become possible to grow rat conceptuses in a culture medium made ip of 90 per cent human serun sipplemented with glucose and 10 per cent rat serum. Embryonic growth and developmental indices achieved in culture, using sipplemented human serum, were reported to be comparable to those observed in whole rat serum (Reti et al., 1982). The successful growth of rat conceptuses during the major part of the organogenetic stage, is an important technical departure, since it enables the effect of potential teratogens, in human serum to be investigated. In order to validate the current embryo culture model, it was demonstrated initially that reproducible embryonic growth and development can be achieved in appropriately prepared serum samples, obtained from healthy women during the various stages of their menstrual cycles, pregnancy and the post-natal period. Furthermore, using serum from patients with ovarian malignancies, on antimitotic chemotherapy, it was demonstrated that the modified vAiole rat embryo culture model is highly sensitive in distinguishing between normal and embryotoxûc human sera.

An investigation of the teratogenic properties of human sera using a mammalian whole embryo culture technique.

During early gestation in the rat, at the time of rapid embryonic differentiation and prior to the full formation of the chorioallantoic placenta, the function of ‘placental’ nutrition was attributed to the yolk-sac by Brunschwig (1927). Such a paraplacental function of the yolk-sac would assume that nutrients pass through the parietal wall into the yolk-sac cavity and thence into the embryo via the visceral yolk-sac epithelium and its underlying vitelline vessels. Supporting this concept were the findings of Everett (1935) who demonstrated in 13-day embryos that toluidine blue was able to pass into the omphalomesenteric vessels more rapidly than it could reach the umbilical veins via the chorioallantoic placenta. Furthermore, the visceral entodermal cells appeared to exert some selectivity in that trypan blue did not pass into the embryo but was localized in the apical cytoplasm. More recently, Padykula, Deren 9 Wilson (1966) demonstrated that the rat yolk-sac concentrated both vitamin B 12 and vitamin B 12 plus intrinsic factor throughout most of gestation.

Ralph Spinuzzi

Papers

Differentiation of alkaline phosphatase and glucose-6-phosphate dehydrogenase in rat yolk-sac.