Increased concurrent immunoreactivity of macrophage markers and HSP47 in the uterus of old multiparous cows

CONTEXT: Declining fertility in aging cows is associated with impaired uterine function, but the relationship between immune remodeling and fibrosis-associated uterine changes remains poorly understood. AIMS: We hypothesized that the uterus of old multiparous cows exhibits coordinated immune-fibrosis-associated remodeling characterized by increased concurrent immunoreactivity of the macrophage markers CD86 and CD163 with HSP47. To test this hypothesis, we quantified CD86-, CD163-, HSP47-, and concurrent immunoreactive profiles throughout the endometrium and myometrium. Additional qualitative αSMA analysis was performed to further characterize CD86/HSP47- and CD163/HSP47-immunoreactive profiles. METHODS: Caruncular (CAR) and intercaruncular (ICAR) endometrium and myometrium were collected from young nulliparous heifers (n = 6) and old multiparous cows (n = 6). Multiplex immunofluorescence with tyramide signal amplification was used to detect CD86, CD163, and HSP47. KEY RESULTS: Concurrent macrophage marker/HSP47-immunoreactive profiles were increased throughout the uterus of old multiparous cows compared with young nulliparous heifers and enriched beneath the luminal epithelium, around endometrial glands, in connective tissue, and in the myometrium. Qualitative analysis further showed αSMA immunoreactivity within many CD86/HSP47- and CD163/HSP47-immunoreactive profiles in the CAR and ICAR. CONCLUSIONS: Compared with young nulliparous heifers, old multiparous cows showed increased concurrent immunoreactivity of macrophage markers with HSP47 throughout the uterus, consistent with coordinated immune-fibrosis-associated remodeling. Qualitative αSMA analysis provides additional support for the fibrosis-associated component of this remodeling. IMPLICATIONS: Coordinated immune-fibrosis-associated remodeling may contribute to age-associated changes in uterine function and represent a potential target for preserving reproductive longevity in cattle.