Mouse Vaginal Opening Is an Apoptosis-Dependent Process Which Can Be Prevented by the Overexpression of Bcl2

Abstract

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.

Characterization of diethylstilbestrol‐induced hypospadias in female mice

“…For example, vaginal opening in mice occurs following apoptosis within the hymen at about 5 weeks of age (Rodriguez et al, 1997). In the present study, the epithelial apoptotic and proliferative indices were examined in the vaginal and urethral regions of DES-exposed mice in order to further understand the cellular mechanisms underlying hypospadias formation.…”

“…However, the developing vaginal lumen progressively extends distally during the neonatal and early postnatal periods. Under normal circumstances, vaginal opening finally occurs around 5 weeks of age following a hormonally-triggered apoptotic event (Rodriguez et al, 1997). Early vaginal opening in rats can also be induced by exogenous 17␤-estradiol or xenoestrogens (Ashby and Tinwell, 1998).…”

Molecular genetic cascades for external genitalia formation: An emerging organogenesis program

“…The labia minora is well developed in humans and not prominent in other species. The proper apoptotic regulation of cell death is required for the regulation of the vaginal opening (Rodriguez et al, 1997). The presence of the vaginal septum often has been found in some specimens of breeding mouse colonies.…”

BAX is involved in regulating follicular growth, but is dispensable for follicle atresia in adult mouse ovaries

“…FSH levels at PN35, around the time of pubertal onset, are equivalent between WT and BaxK/K females, suggesting that rather than affecting hormone production, Bax deletion interferes with apoptosis in the vaginal mucosa. Vaginal opening is an apoptotic event stimulated by estradiol and regulated by BCL-2 family members (Rodriguez et al 1997) and thus, delayed vaginal opening in BaxK/K females is likely due to an absence of Bax in the vaginal mucosa, and defective apoptosis of these cells.…”