TGFB1 is critical for the normal growth of ectopic endometrial tissues, as our previous studies have shown that endometriosis-like lesions from Tgfb1^-/- mice were 11-fold lighter compared to wildtype controls ¹ . Furthermore, in these lesions, macrophage abundance and myofibroblast intensity were reduced by 66% and 47%, respectively, in the absence of host TGFB1.  The goal of this study was to determine if functional macrophage phenotypes and collagen intensity, which is regulated at least partly by macrophage function, were altered in the absence of host TGFB1.

Human endometrial tissues (n=5) were subcutaneously injected into 5 Tgfb1^-/-/SCID mice and 9 Tgfb1^+/+/SCID wildtype (WT) controls. The resulting lesions were collected at day 10 and were frozen in OCT for immunofluorescent staining for macrophage inflammatory markers, MHC Class II and iNOS, pro-tissue remodelling antigens, Arginase 1, scavenger receptor (CD204) and collagen type 1. Quantitative assessment was carried out using ImageJ. 

In total, 5 endometriosis-like lesions were collected from 4 Tgfb1^-/- mice and 9 lesions were collected from WT mice after 10 days. Consistent with our previous study, the lesion weight was significantly lower in the Tgfb1^-/- than the WT controls (Mann Whitney test, p=0.02). The number of MHC Class II- and iNOS-positive cells was significantly reduced in the lesions from Tgfb1^-/- compared to controls (p<0.001 and p<0.01, respectively). Similarly, the number of CD204-positive cells was significantly decreased in Tgfb1^-/- mice, however no difference was seen in Arginase 1-positive cell number. Lesions from Tgfb1^-/- mice also had lower collagen 1 intensity than those from WT (p<0.01).

We conclude that host TGFB1 deficiency is associated with a reduction in markers of macrophage activity as well as collagen density. This suggests that macrophages are central to the mechanism by which the growth of endometriosis-like lesions is controlled by host TGFB1 bioavailability. Ongoing experiments will examine whether this reflects a global reduction in macrophages or a proportional alteration in the phenotype of macrophages in Tgfb1^-/- mice.