Stromal induction and specification of morphogenesis and cytodifferentiation of the epithelia of the mullerian ducts and urogenital sinus during development of the uterus and vagina in mice

Abstract

Homotypic and heterotypic recombinations were preapred with trypsin-separated epithelium and stroma from uterus of 1- to 9-day-old and vagina of 2- to 150-day-old mice. Growth of homotypic recombinants in adult female hosts resulted in normal uterine and vaginal morphogenesis. Heterotypic recombinants composed of uterine stroma and vaginal epithelium (VE) usually formed uterus, while recombinants composed of vaginal stroma and uterine epithelium (UE) usually underwent vaginal morphogenesis. The developmental responses of these heterotypic recombinants was age-dependent. Epithelia (UE and VE) from mice two to five-days old were responsive to stromal induction. However, from days 5 to 9 postpartum a progressive loss in competence was observed in both epithelia, and vaginal epithelium nine or more days old was unresponsive to heterotypic inductors. Inductive activities of uterine stroma were demonstrated in 2- to 7-day-old neonates and of vaginal stroma in 2- to 150-day-old mice. These results indicate that establishment of the regional specification of Mullerian and sinus epithelium during uterine and vaginal morphogenesis is due to inductive activities of the stroma.

Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium

“…We developed an in vivo murine endometrial regeneration model from dissociated uterine stromal and epithelial cells. Endometrial glands from reproductive-age female mice were harvested as previously described (7,8) and dissociated (Fig. 1A).…”

“…Uterine epithelial and stromal separation was performed as previously described (7,8). Uterine epithelial sheets were digested in 0.8 mg/mL collagenase (Invitrogen; 17018-029) in DMEM/10% FBS by incubation at 37°C with gentle agitation.…”

“…Previous studies demonstrated that recombined uterine tissue fragments implanted subrenally could regenerate into endometrial-like glands (7,8). The inability to genetically manipulate tissue fragments limits the utility of this model system.…”

Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure

“…The development of cervicovaginal adenosis has been attributed to aberrant cell-fate determination in which some vaginal epithelial cells acquire a uterine fate and become a simple columnar epithelium rather than a stratified squamous one [57]. The mesenchyme plays a major role in this epithelial fate determination process [58]. DES may also act directly on the vaginal epithelial cells by blocking the expression of p63, a protein that plays a major role in the fate determination of the vaginal and other stratified squamous epithelia [57].…”

“…DES may also act directly on the vaginal epithelial cells by blocking the expression of p63, a protein that plays a major role in the fate determination of the vaginal and other stratified squamous epithelia [57]. More recently, msx2 which plays a critical role in cell fate determination in the vaginal epithelium, was shown to be repressed by DES [58]. This homeodomain transcription factor is required for the correct expression of wnt7a, and the absence of msx2 would result in a complete failure of stratification of the vaginal epithelium [59].…”