Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice.
Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice.
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DOI：
10.1093/biolre/ioz002
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发表时间：
2019-01
影响因子：
3.6
通讯作者：
S. Yellon;E. Greaves;A. C. Heuerman;A. Dobyns;J. Norman
中科院分区：
文献类型：
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作者：
S. Yellon;E. Greaves;A. C. Heuerman;A. Dobyns;J. Norman
为了检验巨噬细胞是重塑子宫颈为出生做准备所必需的假设，在繁殖后第14天和第16天给妊娠纯合子CD 11b-dtr小鼠注射白喉毒素（DT）。在繁殖后第15天，巨噬细胞（F4/80+）在子宫颈和肾脏，但不是在肝脏，卵巢，或其他非生殖组织DT相比，盐水处理的dtr小鼠或野生型对照DT或盐水耗尽。在DT治疗的24小时内，与对照组相比，dtr小鼠宫颈基质中细胞核和巨噬细胞的密度下降，但胶原蛋白的双折射（作为细胞外交联结构的指示）保持不变。仅在DT处理的dtr小鼠的宫颈中，巨噬细胞中的凋亡形态明显。DT治疗未改变中性粒细胞的稀疏存在或形态。在繁殖后第18天，巨噬细胞在DT处理的dtr小鼠的子宫颈中重新繁殖，使得这些数量与对照组相当。然而，在足月时，在大多数给予DT的dtr小鼠中出现了无宫颈成熟的胎儿死亡证据-这可能是治疗对胎盘功能的影响。这些发现表明，CD 11b + F4/80+巨噬细胞对维持妊娠很重要，并且是重塑宫颈以准备分娩的过程所必需的。
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.