Erythropoietin contributes to implantation: ectopic hemoglobin synthesis in decidual cells of mice.
Erythropoietin, by binding to its receptor, stimulates definitive erythroblasts to accumulate hemoglobin (Hb) by up-regulating erythroid-specific genes and causes differentiation of erythroblasts into erythrocytes. In mouse decidua we have found the expression of transcripts for the erythropoietin receptor, the function of which has not yet been elucidated. Erythropoietin signaling was inhibited by the injection of a soluble form of the erythropoietin receptor capable of binding with erythropoietin into the mouse uterine cavity on day 4 of gestation, and pale and defective decidual bodies appeared three days later. These pale decidual bodies contained defective embryos without extension to the ectoplacental region, while normal reddish decidual bodies contained normal developing embryos and expressed embryonic and adult Hb with characteristic location of the respective hemoglobins in which an epsilon- or beta-globin signal was confirmed. Furthermore, blocking of erythropoietin signaling destroyed Hb-containing cells and resulted in apoptosis that caused embryonic death. Thus, erythropoietin-mediated Hb synthesis is essential for the survival of decidual cells. In addition, although no transcripts for GATA-1 and erythroid heme enzymes could be detected, genes for beta-globin, as well as non-specific delta-aminolevulinate synthase, were expressed and regulated in an erythropoietin-dependent manner. This is the first evidence that ectopic Hb synthesis exists and that erythropoietin coregulates erythroid (globin) and nonerythroid (delta-aminolevulinate synthase) genes.
Yasuda
Yoshiko
Y
Department of Anatomy Division 1, Kinki University School of Medicine, Osakasayama, Osaka, Japan. y1126yas@med.kindai.ac.jp
Sasaki
Tohru
T
Takagawa
Masanori
M
Maeda
Mitsuyo
M
Yasuda
Megumi
M
Atsumi
Tadao
T
Fujita
Yoshihiko
Y
Fujita
Hiroyoshi
H
D000624:5-Aminolevulinate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D010064:Embryo Implantation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006441:Hemoglobin A / Q000096:biosynthesis; D006446:Hemoglobin E / Q000096:biosynthesis; D006454:Hemoglobins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014599:Uterus / Q000378:metabolism
D006454:Hemoglobins; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D004921:Erythropoietin; D006441:Hemoglobin A; D006446:Hemoglobin E; D000624:5-Aminolevulinate Synthetase