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Summary.

A segment of the uterus in seven ferrets was isolated surgically before mating. The endometrium of this segment was traumatized at laparotomy 12 days after mating. Histological and electron microscopic examination of the traumatized endometrium 8 days later showed the development of a maternal pregnancy reaction. This was identical to the endometrial response resulting from the presence of normal trophoblast at an implantation site. It consisted of the formation and subsequent necrosis of symplasmal nests of endometrial epithelium and hypertrophy of the cells lining the endometrial capillaries. The capillary cells were cubical or columnar in shape and had a well-developed rough endoplasmic reticulum and Golgi apparatus, suggesting a secretory function. The cells appeared to produce a thick acid mucopolysaccharide membrane which might normally play a part in embryonic nutrition.

Traumatization of similarly isolated segments of the uterus in ferrets during oestrus and anoestrus resulted in no specific response.

The interaction between parathyroid hormone-related protein (PTHrP) and the parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth and differentiation of various tissues throughout fetal development in the rodent. The aim of the present study was to define the patterns of expression of PTHrP and of the PTH/PTHrP receptor in the rat uterus during the early stages of normal pregnancy, and following artificial induction of a decidual reaction. Using hybridization histochemistry, we have shown that the receptor gene is switched on early in pregnancy (by 1.5 days post coitum) in the endometrial stromal cells that surround the lumen. These cells include the anti-mesometrial subepithelial stromal cells that are destined to become decidualized. This pattern continues until 5.0 days post coitum, when PTHrP is switched on in antimesometrial luminal epithelial cells that line the implantation chamber. Stromal cells underlying the implantation chamber then downregulate transcription of the receptor gene, and within 12 h differentiate into decidual cells. A similar pattern was seen in uteri in which a decidual reaction had been induced artificially. Therefore, it may be postulated that in early pregnancy the endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some time after receiving the signal, the endometrial stromal cells downregulate the receptor gene, and this appears to be a trigger for the terminal differentiation of the stromal cells into decidual cells. These results suggest that PTHrP, acting through the PTH/PTHrP receptor, plays a role in the initiation of a decidual reaction during early pregnancy by regulating the differentiation of endometrial stromal cells into decidual cells.

Traumatization of an isolated segment of the ferret uterus on Day 12 of gestation (the day of implantation) results in the development of a maternal pregnancy reaction at the site of the trauma. This reaction consists of the formation and subsequent necrosis of symplasmal nests of endometrial epithelial cells and hypertrophy of the maternal capillary endothelium, and the cytology is identical to that of the endometrial reaction in the placental region of the uterus during normal pregnancy (Beck, 1974). The development of a maternal pregnancy reaction at times during gestation other than Day 12 has not been investigated and the present study was therefore undertaken to see whether a sensitive period existed.

Hybridization histochemistry and solution hybridization studies were performed to localize the expression of parathyroid hormone-related protein (PTHrP) during implantation in rats. Parallel studies were performed on rat uteri bearing oil-induced deciduomata and on cultured blastocysts. PTHrP mRNA begins to be expressed at day 5.5 of gestation by the uterine epithelium in the anti-mesometrial crypts marking the sites of implantation and in comparable regions during induction of deciduoma. Trophoblastic giant cells express the gene as soon as they are phenotypically recognizable both in vivo and in culture, but PTHrP mRNA cannot be detected in the early blastocyst or in cells of the inner cell mass. Decidual cells produce PTHrP mRNA both in normal gestation and after the induction of deciduomata. In each case, the expression of the gene in decidual cells follows its expression in uterine epithelium by 48 h. The uterine topographical location and time of expression of the PTHrP gene suggests that it plays a part in the implantation of the blastocyst.

Summary. Rat embryos together with their visceral yolk sac were grown in vitro during the early period of organogenesis from days 9·5 to 11·5 and the ultrastructural morphology of the visceral yolk sac cells was compared with that in vivo at the beginning and at the end of the culture period. Identical areas of the visceral yolk sac endodermal cells were analysed morphometrically. A measure of the functional activity was obtained by comparison of the volume density and surface density of the vacoular system. At 9·5 and 11·5 days, the values obtained were virtually identical for yolk sacs in vivo and in vitro. At 9·5 days, the volume and surface density of the endocytotic vacuoles in the embryonic endoderm was significantly lower than in the visceral yolk sac endoderm.

It is concluded that the digestive function of the yolk sac is almost certainly identical in culture and in vivo and that the cells of the embryonic endoderm do not take a significant part in embryonic nutrition.