Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis.
We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.
Medlock
E S
ES
Department of Experimental Hematology, Amgen Inc, Thousand Oaks, CA 91320.
Kaplan
D L
DL
Cecchini
M
M
Ulich
T R
TR
del Castillo
J
J
Andresen
J
J
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007958:Leukocyte Count; D008099:Liver / Q000166:cytology; D008431:Maternal-Fetal Exchange; D009504:Neutrophils / Q000166:cytology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor