Expression of rat transforming growth factor alpha mRNA during development occurs predominantly in the maternal decidua.

Abstract

Previous studies have shown that transforming growth factor a is expressed during rodent development. To establish the site(s) of transforming growth factor a mRNA expression during rat embryogensis, we performed in situ hybridization and Northern blot analyses on samples of embryonic and maternal tissues at various gestational ages. Our results indicate that the high levels of transforming growth factor a mRNA that are observed during early development are the result of expression in the maternal decidua and not in the embryo. Decidual expression appears to be induced after implantation, peaks at day 8, and then slowly declines through day 15 at which time the decidua is being resorbed. Expression of transforming growth factor a mRNA is highest in that region of the decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and other maternal tissues. The developmentally regulated expression of transforming growth factor a mRNA in the decidua, together with the presence of epidermal growth factor receptors in this tissue, suggests that transforming growth factor a stimulates proliferation locally through an autocrine mechanism. Since epidermal growth factor receptors are present in the embryo and placenta, transforming growth factor a produced in the decidua may also act on these tissues through paracrine or endocrine mechanisms.Transforming growth factors (TGFs) are polypeptides, first purified from retrovirus-transformed cells in culture, that have been shown to confer on cultured normal cells phenotypic properties associated with transformation (4, 27). These reversible alterations include changes in morphology, the loss of contact inhibition, and the acquisition of growth in soft agar. Two distinct TGFs have been described: TGFa and TGFP. TGFa is a single polypeptide of 50 amino acids that shares 30% sequence homology with epidermal growth factor (EGF) (17) and exerts its biological action by binding to the EGF receptor (5, 22). TGF,B is an unrelated homodimer of 112 amino acids that does not bind the EGF receptor (6,18,26). Interactions between TGFa and TGF, are complex, with the outcome depending on the cell type examined; e.g., in fibroblasts grown in soft agar, TGF, potentiates the mitogenic action of TGFa (and EGF) and does not act as a mitogen itself (19,25). In view of their biological actions and the finding that human and rodent TGFs are expressed by a variety of transformed as well as tumor cells, it has been proposed that these proteins play a role in the growth of some tumors through autocrine and paracrine mechanisms (31).cDNAs encoding both human (8) (21) showed that mouse embryos between days 11.5 and 17.5 of gestation contained more EGF-like material than could be accounted for by an EGFspecific radioimmunoassay. Using radioreceptor assays and bioassays, Twardzik (32) subsequently demonstrated a high level of TGFa in day 7 mouse embryos. This high level then declined and was followed by a smaller peak at day 13. Similarly, we have previously shown that rat embryos at...

Molecular cloning of mouse epiregulin, a novel epidermal growth factor‐related protein, expressed in the early stage of development

“…The expression of epiregulin was limited to 7-day-old embryo, and was very low or undetectable in 9-to 17-day-old embryos. Similar expression profiles during fetal development have been reported in those of TGF-c~ [19][20][21][22]. The highest expressions of mouse and rat TGF-c~ are observed on day 7 to 9 [19] and on day 8 to 9 [20], respectively, but diminish after that to undetectable levels.…”

Progranulin (acrogranin/PC cell‐derived growth factor/granulin‐epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development

“…The expression of progranulin in the placenta resembles that of TGFalpha, which is also abundant in the decidualizing stroma and declines after day 8 (Han et al, 1987(Han et al, , 1988. In the 8.5 day embryo, progranulin expression was observed in the proliferating neuroepithelium, mesenchyme, and ectodermal cells (Fig.…”

The mouse waved-2 phenotype results from a point mutation in the EGF receptor tyrosine kinase.

“…Total RNA was isolated and subjected to Northern analysis as described previously (Han et al 1987). Two overlapping 2-kb cDNAs corresponding roughly to the extracellular and intracellular domains of the EGF receptor were generated by reverse transcription of 1 p,g total liver RNAs and subsequent PCR amplification ).…”