Erythropoietin Ameliorates Damage to the Placenta and Fetal Liver Induced by Exposure to Lipopolysaccharide

Transverse sections of placenta from control (A, D, G), LPS alone (B, E, H) and LPS + rhEPO (C, F, I) fetal sheep at 116 days' of gestation stained with von Kossa's stain for calcium deposits and counterstained with haematoxylin and eosin. In control fetuses there was no signs of overt tissue injury (A,D,G) with the fetal and maternal tissues being closely associated (G). Positive von Kossa staining, indicative of tissue injury (black precipitate), was present in fetuses exposed to LPS alone (B, E). This was associated with oedema in the fetal villus tissue (E, asterisks) and increased intervillous spaces (E, H arrow heads) and apoptosis in fetal tissues (H, arrows). Less damage occurred in LPS-exposed fetuses treated with rhEPO (C, F, I). Ki67-IR (arrows) in control (J), LPS alone (K) and LPS + rhEPO (L) illustrating a higher density in LPS + rhEPO fetuses. M, maternal tissue; F, fetal tissue; F&M, interdigitated fetal and maternal tissue. Scale bars: A-C = 500 μm; D–F = 100 μm; G-L = 20 μm.

Transverse sections of the liver stained with haematoxylin and eosin (A, B, D, E, G, H) or Ki-67-IR for cell proliferation (C, F, I) in control (A–C), LPS alone (D–F) and LPS + rhEPO (G–I) fetuses. In control fetuses (A, B) plates of hepatocytes were arranged around the central vein (asterisks). In fetuses exposed to LPS alone, tissue necrosis (D, arrow heads) was present usually distributed around the central vein (D, E); necrosis was not seen in LPS + rhEPO fetuses (G, H). LPS exposure results in increased cell proliferation (F, brown cells) compared to control (C); cell proliferation was further enhanced in fetuses treated with rhEPO following LPS (I). Scale bars: A, D, G = 500 μm; B, E, H = 20 μm; C, F, I = 50 μm.