Interleukin-5 transgene expression and eosinophilia are associated with retarded mammary gland development in mice

Abstract

Eosinophils are prevalent in the female reproductive tract, where they may contribute to regulation of development and maintenance of epithelial integrity. The present study examined the effects of constitutive interleukin-5 (IL-5) expression and overabundance of eosinophils on the development and function of the mammary gland, uterus, and ovary in mice. Eosinophils were up to 13-fold and 4-fold more abundant in the uterus and mammary gland, respectively, in female IL-5 transgenic (IL-5Tg) mice than in wild-type (Wt) animals. Eosinophils were present in large numbers in regressing corpora lutea in IL-5Tg mice but not in ovaries from Wt mice. Postpubertal mammary gland development was retarded in IL-5Tg mice, with impaired terminal end bud formation and an altered pattern of epithelial cell proliferation across the mammary fat pad coincident with disrupted ductal branching and extension. By 10 wk of age, the ductal tree was complete in both genotypes. Onset of first estrus was also delayed in IL-5Tg mice, but once IL-5Tg mice reached puberty, serum estrogen content across the cycle and estrous cycle duration were normal. The histology of uterine tissue and epithelial cell turnover were unchanged. Capacity to mate and achieve pregnancy was not affected by maternal IL-5 transgene expression, although at Day 18 of gestation, a modest decrease in the fetal:placental weight ratio was observed. Furthermore, parturition and ability to lactate and nurture postnatal pup development were not compromised. These data demonstrate an effect of IL-5 overexpression on ductal morphogenesis during postpubertal mammary gland development that is consistent with a direct regulatory role for eosinophils in these events, but these data also show that eosinophil excess does not have long-term consequences for adult reproductive function.