Mouse vaginal opening is an apoptosis-dependent process which can be prevented by the overexpression of Bcl2.
In the mouse, opening of the vaginal cavity to the skin is a late event, occurring around the fifth week of life; it can be induced in sexually immature mice by beta-estradiol injections. We have generated two lines of transgenic mice expressing the human Bcl2 protein in a variety of tissues. The vaginal cavity of the transgenic females remained permanently closed, a condition completely resistant to beta-estradiol injections; this was accompanied by a considerable distension of the genital tract. Histologic studies of vaginal sections at the time of opening to the skin in normal mice showed, by the TUNEL method which detects nuclei with fragmented DNA characteristic of apoptosis, that this event coincides with extensive apoptosis in the lower part of the vaginal mucosa, a process prevented in the bcl2 transgenic mice, which express Bcl2 in suprabasal epithelial cells and in subepithelial cells of the vaginal mucosa. In contrast, two lines of mice bearing a Bcl2 transgene placed under the control of a K10 keratin promoter, whose expression is restricted to the suprabasal layers of the epidermis, had a normal phenotype. Eyelids' formation and opening of the external ear canals, which also occur after birth in the mouse, were not altered in any of these transgenic lines; histological study of eye and ear sections at the time of these events failed to detect apoptosis. In conclusion, the tissue remodeling required to complete maturation of the mouse female genital tract at the time of puberty is an hormonally triggered apoptosis-dependent process.
Rodriguez
I
I
Department of Pathology, Centre Médical Universitaire, University of Geneva, Switzerland.
Araki
K
K
Khatib
K
K
Martinou
J C
JC
Vassalli
P
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry; D006801:Humans; D053550:Keratin-10; D007633:Keratins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000737:chemistry; D009928:Organ Specificity; D010053:Ovary / Q000637:transplantation; D010735:Phosphoglycerate Kinase / Q000235:genetics; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014621:Vagina / Q000737:chemistry / Q000166:cytology / Q000254:growth & development*
C507493:KRT10 protein, human; C507491:Krt10 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D053550:Keratin-10; D004958:Estradiol; D007633:Keratins; D010735:Phosphoglycerate Kinase; D010751:Phosphopyruvate Hydratase