α1A‐adrenergic receptor is required for normal prostate development and successful conception in mice

Abstract

In the prostate, α1A‐adrenergic receptor (α1A‐AR) mediated smooth muscle contraction is essential for normal function. Conversely, in benign prostate hyperplasia, α1‐AR antagonists are used to block smooth muscle contraction and provide relief from urinary symptoms. This identifies a clear role for α1‐ARs, particularly the α1A‐AR, in the prostate, but less is known about how α1‐ARs regulate prostate development. While breeding α1‐single and double knockout (α1AKO, α1BKO, α1ABKO) mice, we observed that α1AKO‐breeding pairs were significantly (P<0.01) less successful in establishing a pregnancy. Pairing α1AKO mice with WT or α1ABKO mates demonstrated that the lack of successful pregnancies was due to dysfunction in α1AKO males, not females. Gross dissection of the urogenital track in adult α1AKO males revealed distinct discoloration of seminiferous tubules and under‐developed prostate glands. Further, histologic analysis of serial prostate sections stained with hematoxylin and eosin isolated from WT and α1AKO male mice 3–12 weeks of age indicated abnormalities in prostates isolated from α1AKO males as early as 3 weeks of age. A lack of stromal development, thinning of epithelium, and fluid retention was observed in α1AKO prostates at all ages. These data indicate that the α1A‐AR is required for normal prostate development and function. NIH (TDO and CDW) and the PhRMA Foundation (CDW) supported this work.