Journal
BIOLOGY OF REPRODUCTION
Volume 100, Issue 5, Pages 1386-1394Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioz002
Keywords
parturition; diphtheria toxin; collagen; monocytes; ripening; preterm birth
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Funding
- NIH [HD954931]
- All Disciplines Scholar award
- Department of Pediatrics Research Fund
- MRC [MR/M009238/1, MR/M009238/2, MR/N022556/1] Funding Source: UKRI
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To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT-compared to saline-treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT-a possible consequence of treatment effects on placental function. These findings suggest that CD11b(+) F4/80(+) macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition. Conditional depletion of macrophages in CD11b-dtr mice during the critical period for cervix remodeling interfered with ripening and the progress of pregnancy.
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