Induction of avascular yolk sac due to reduction of basic fibroblast growth factor by retinoic acid in mice

• Published in: Developmental biology Vol. 150; no. 2; pp. 397 - 413
• Main Authors: Yasuda, Yoshiko, Nishi, Nozomi, Takahashi, Jun A., Konishi, Hiroyoshi, Ohara, Ikuko, Fujita, Hiroko, Ohta, Mitsuhiro, Itoh, Nobuyuki, Hatanaka, Masakazu, Tanimura, Takashi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-04-1992; Elsevier
• Subjects: Acid Phosphatase - metabolism; alpha 1-Antitrypsin - metabolism; Animals; Antibodies; Biological and medical sciences; Blotting, Northern; DNA Probes; Embryology: invertebrates and vertebrates. Teratology; Embryonic and Fetal Development; Female; Fibroblast Growth Factor 1 - genetics; Fibroblast Growth Factor 1 - metabolism; Fibroblast Growth Factor 2 - antagonists & inhibitors; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Fundamental and applied biological sciences. Psychology; Lysosomes - enzymology; Mice; Mice, Inbred ICR; Microscopy, Electron; Microscopy, Immunoelectron; Pregnancy; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Fibroblast Growth Factor; RNA - genetics; RNA - isolation & purification; RNA, Messenger - genetics; RNA, Messenger - isolation & purification; RNA, Messenger - metabolism; Teratology. Teratogens; Tretinoin - pharmacology; Yolk Sac - blood supply; Yolk Sac - drug effects; Yolk Sac - physiology; Yolk Sac - ultrastructure; Embryonic development; Fibroblast growth factor; Endothelial cell; Embryo; Fetal membrane; Rodentia; Vitamin; Retinoids; Vascularization; Yolk sac; Vertebrata; Mammalia; Mouse; Blood vessel; Enzymatic digestion; Teratogen; Retinoic acid; Biological receptor
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/0012-1606(92)90251-B

Vasculogenesis depends on autocrine secretion of basic fibroblast growth factor (bFGF) from capillary endothelial cells. Retinoic acid (RA) induced avascular yolk sac (AVY) of mouse embryos of dams given 60 mg/kg of RA orally on Day 8 of gestation and sacrificed 3 days later. We studied the localization and transcriptional expression of bFGF and FGF-receptor (flg), heparin-binding growth factor (HBGF) activity, localization of lysosomal enzymes and
α
1-antitrypsin (AAT), and electron microscopy of the normal mouse visceral yolk sac (VYS) and AVY. bFGF, which is normally present in the endoderm of the VYS of 8-day-old embryos and in all components of the VYS by Day 11 of gestation, was reduced in the AVY. However, in the presence of bFGF
in vitro capillary nets were restored in the AVY. The mRNA for bFGF was not detectable in either VYS or AVY, while flg mRNA was detected equally in both organs in Northern blotting. The characteristic distribution pattern of lysosomal enzymes, acid phosphatase, lysozyme, and cathepsin D, and AAT was altered in the AVY. The level of acid phosphatase and AAT was reduced to 10% in the AVY. Electron microscopy revealed a partial or total loss of lysosomal membranes where the contents of lysosomes fused with adjacent lysosomes and the external organelles. These results suggest that vitelline blood vessels are not developed by endogenous autocrine bFGF but by exogenous transcellular bFGF from absorptive endodermal cells. Retinoic acid does not affect the angiogenic capacity of the VYS mesenchyme but destroys lysosomes, which release hydrolytic enzymes, leading to degradation of AAT in the endodermal cells and then digestion of endocytosed bFGF.