Figure 4. Infertility in macrophage-depleted Cd11b-Dtr mice results from implantation failure.
(A) Trypan blue clearly delineates bands of increased vascular permeability in the uterus, showing embryo implantation sites in some, but not all, macrophage-depleted Cd11b-Dtr mice (arrows) on day 4.5 pc (upper right), 24 hours after i.p. injection with DT (25 ng/g) on day 3.5 pc, compared with the majority of wild-type mice given DT (upper left). By day 5.5 pc, 48 hours after DT injection, no evidence of implantation was observed in any Cd11b-Dtr mice compared with normal implantation sites in wild-type mice. (B) The numbers of implantation sites per mouse at day 4.5 pc and day 5.5 pc are shown for wild-type mice (WT +DT) and macrophage-depleted Cd11b-Dtr mice (Cd11b- +DT), after injection of DT on day 3.5 pc. Data are number of implantations per mouse, with mean ± SEM superimposed. The number of mice per group is shown in parentheses. *P < 0.05, ** P < 0.01, Cd11b- +DT versus WT +DT. (C) Sections of uterus (H&E) from Cd11b-Dtr mice on day 4.5 pc (24 hours following DT injection) show that blastocyst-stage embryos (arrows) were attached laterally or in the middle of an open lumen with no decidual zone (10/12 embryos; middle panel), or less frequently were attached with a decidual zone, but incomplete uterine closure (2/12 embryos; right panel). This compared with wild-type mice, in which typical implantation sites in a narrowed endometrial lumen, with surrounding decidual zone, were consistently evident (left panel). Images are representative of 10–12 embryos in 4 WT and 5 Cd11b-Dtr mice. Insets are high-power. Lu, lumen; ICM, inner cell mass; TE, trophectoderm; DZ, decidual zone. Scale bars: 50 μm.