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Granulocyte colony-stimulating factor crosses the placenta and stimulates
fetal rat granulopoiesis
ES Medlock, DL Kaplan, M Cecchini, TR Ulich, J del Castillo and J Andresen
Department of Experimental Hematology, Amgen Inc, Thousand Oaks, CA 91320.
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.
Volume 81,
Issue 4,
pp. 916-922,
02/15/1993
Copyright © 1993 by The American Society of Hematology

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