Abstract
<title>Abstract</title> <p>In adult females of most hystricomorph rodents (animals in the suborder Hystricomorpha, such as guinea pigs), the vagina is open only during heat period; for the remainder of the estrous cycle, it is occluded by a structure resembling the human hymen—known as the "vaginal closure membrane" (VCM). This process of periodic formation and regression of the VCM persists throughout the animal's entire life, from puberty until death. To date, the underlying mechanisms explaining why only this small subset of rodents periodically forms a VCM remain largely unelucidated. In this study, we compared the epithelium structure around the external vaginal orifice between guinea pigs and mice, revealed that a hairless epidermal transition zone exists in guinea pig but not mice. The proliferation of keratin (Krt) 10-positive epithelial cells in this zone plays key roles in VCM formation. Hormone treatment in ovariectomized guinea pigs revealed progesterone may promote the formation and thickening of VCM. Ki67 cytoplasmic localization and strong expression of progenitor cell marker Krt19 in epithelial cells at external vaginal orifice of guinea pigs but not mice indicated that the VCM formation in guinea pigs is most likely a tissue remodeling process. And in addition, we identified a novel population of stem cells expressing pluripotency markers at the external vaginal orifice of guinea pigs. Our findings suggest that, in guinea pigs, pluripotent stem cells may reside within the epithelial tissue of the vaginal opening region of adult females and is responsible for VCM formation.</p>