Expression and regulation of androgen receptor in the mouse uterus during early pregnancy and decidualization

Abstract

The androgen receptor (AR) is a ligand-activated transcription factor that is important for both the male and female reproductive systems. The expression and regulation of AR in the uterine endometrium during early pregnancy and decidualization remain relatively under-investigated, so we sought to immunohistochemically examine the spatiotemporal expression of AR in mouse uteri during the peri-implantation period as well as in response to specific steroid hormones. AR protein was found in the nuclei of uterine stromal cells starting on pregnancy Days 1 and 2, with its abundance increasing on Days 3 and 4. From pregnancy Days 5 to 9, however, the expression of AR markedly declined in stromal zones of uteri. No signal was detected in the decidualized cells surrounding the site of embryo implantation; moreover, no AR immunostaining was observed in decidualized uterine cells in an artificial oil-induced model of decidualization. Progesterone significantly inhibited AR protein expression, whereas estrogen dramatically elevated AR abundance in the stroma of ovariectomized mouse uteri. Taken together, our results are the first to demonstrate that decidualization and progesterone significantly inhibited the AR protein expression in vivo, whereas estrogen increased AR protein levels in the stromal cells of mouse uteri. These responses might be advantageous for the proliferation and differentiation of uterine stroma and for embryo implantation during early pregnancy.

How do elevated levels of testosterone affect the function of the human fallopian tube and fertility?—New insights

“…Also, androgen‐induced signaling cascades may have a role in stromal decidualization by regulating matrix metalloproteinases, prolactin, and insulin‐like growth factor‐binding protein 1 (Cloke & Christian, ; Cousins et al, ; Gibson, Simitsidellis, Cousins, Critchley, & Saunders, ; Ishikawa, Harada, Kubota, & Aso, ; Kajihara et al, ). In vivo studies in mice and rats as well as in vitro studies in humans and mice show that androgen administration increases myometrial proliferation (Kim et al, ; Lan et al, ; Liu et al, ; Makieva et al, ; Perusquía, Navarrete, Jasso‐Kamel, & Montaño, ; Simitsidellis, Gibson, Cousins, Esnal‐Zufiaurre, & Saunders, ; Xu et al, ).…”

Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages

“…In the mice uterus, quantitative in situ hybridization identified uniform labeling of androgen receptor (AR) mRNA in all compartments, including the epithelium [ 10 ]. A recent study described nuclear stromal AR staining in the mouse uterus but was not detected in the luminal or glandular epithelium [ 11 ]. Female global AR knockout mice are sub-fertile [ 12 ].…”

A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

“…In the uteri of mice, quantitative in situ hybridization detected uniform labeling of Ar mRNA in all compartments, including the epithelium ( 14 ). A recent study reported nuclear stromal AR staining in the mouse uterus but AR was not detected in the luminal or glandular epithelium ( 15 ). A study using a transgenic mouse model of an androgen response element construct fused to a luciferase reporter revealed strong AR activity in the uterus, with the antiandrogen bicalutamide inhibiting luciferase activity ( 16 ).…”