Lack of plasminogen leads to milk stasis and premature mammary gland involution during lactation.
The extracellular serine protease, plasmin, is activated from its precursor, plasminogen (Plg), by the urokinase-type and tissue-type Plg activators (uPA and tPA respectively). One of the main plasmin substrates, fibrin, is formed from fibrinogen via thrombin activity. We have previously shown that mice deficient for Plg are strikingly less able to support a litter during lactation compared to wild type mice. Here we suggest a mechanism responsible for this lactation defect. Reduced epithelial content and increased apoptosis are observed in Plg-deficient mammary glands at lactation day 7. Immunofluorescence analysis reveals the presence of fibrin(ogen) in the stroma surrounding mammary alveoli and adipocytes and identifies fibrin(ogen) as a component of breast milk in both wild type and Plg-deficient mice. Furthermore, a large accumulation of fibrin(ogen) together with apoptotic epithelial cells is observed in the lactating mammary alveoli and ducts of some Plg-deficient mice. This suggests that fibrin plays a key role in the malfunction of mammary glands in the absence of Plg, possibly through blockade of mammary ducts inducing milk stasis, inhibiting milk expulsion and thereby inducing premature apoptosis and involution.
Green
Kirsty A
KA
Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
Nielsen
Boye S
BS
Castellino
Francis J
FJ
Rømer
John
J
Lund
Leif R
LR
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001485:Basement Membrane / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006579:Heterozygote; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000172:deficiency*
D010446:Peptide Fragments; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen