Figure 3.

Genitourinary (GU) tract histopathologic findings in VEH- and ActRIIB-mFc–treated mice. A and B: Gross and histologic evidence of urethral obstruction leading to bladder distension, inflammation (asterisk) and necrosis in a subset of Acta1 H40Y mice that died spontaneously during the trial. C and D: Assessment of copulatory plugs. C: Axial section of the GU tract of an ActRIIB-mFc–treated Acta1 H40Y mouse at 16 weeks of age. A copulatory plug is evident, as is a large amount of urethral striated muscle surrounding the prostate. There is no evidence of inflammation or tissue necrosis in this specimen. D: Quantification of mice exhibiting intraurethral copulatory plugs out of (n) mice per group. E: Quantification of mice exhibiting GU tissue inflammation out of (n) mice per group. F and G: Immunostaining of urethral striated muscles for skeletal muscle actin reveals pathologic aggregates of actin (corresponding to nemaline rod aggregates) in numerous fibers in Acta1 H40Y mice (G), whereas these aggregates are absent in WT littermates (F). H: Frequency histogram illustrating myofiber size distribution in urethral striated muscles of VEH- and ActRIIB-mFc–treated mice. ^∗P < 0.05, ^∗∗∗P < 0.001. ActRIIB, ActRIIB-mFc treated; VEH, vehicle; WT, wild type.