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PubMed1976

Clear cell adenocarcinoma of the cervix and vagina. A clinicopathologic study of 21 cases with and without a history of maternal ingestion of estrogens.

Twenty-one cases of clear cell adenocarcinoma of the cervix and vagina have been reviewed. Fifteen cases occurred in females under 25 years of age and four in women over 45 years. In seven cases, a positive history of maternal ingestion of diethylstilbestrol (DES) was obtained. One mother gave a history of medication with conjugated estrogens and ethisterone. Of the 13 patients with a negative history, three were born during the time period when DES was commonly used to prevent abortion. Fifteen carcinomas were cervical in origin; seven of these also involved the vagina. In six cases the carcinoma was entirely vaginal. Vaginal involvement of the carcinomas was more common in the estrogen-related group. Two non-estrogen-related cases had coexisting congenital malformations with double uterus and vagina and unilateral renal agenesis. The histopathologic appearance was similar in both groups. In most cases, a mixture of papillary, microcystic, tubular, and solid features was seen. Vaginal adenosis was found in nine cases, six of which were estrogen-related. Surgical therapy was employed in most cases and was generally superior to radiation therapy. Five patients had lymphatic involvement. All died from carcinoma. The survival rate among sixteen patients followed for 2 years or more was 62.5%. The probable müllerian origin of clear cell adenocarcinoma is discussed. It is suggested that DES, by virtue of being an estrogen, interferes with the normal process of differentiation and degeneration of müllerian epithelium in the fetal vagina. The persistence of müllerian cells altered at the subcellular level could form the basis for development of carcinoma in later life. However, a similar sequence of events must also be accepted to occur "spontaneously" since clear cell adenocarcinoma can develop in women without a history of maternal estrogens.

Adenocarcinoma↗

PubMed1991

Double vagina, cardiac, pulmonary, and other genital malformations with 46,XY karyotype.

We have studied two unrelated genetic males with a novel constellation of genital, cardiac, and pulmonary malformations. The genital abnormalities consisted of a true double vagina, retention of Müllerian structures, and undervirilization of the external genitalia. Both infants had complex cyanotic congenital heart defects, hypoplastic right lungs, anomalous pulmonary venous return, and abnormalities of the diaphragm. One patient had rhabdomyomatous dysplasia of the lungs. The cause of this malformation pattern is unknown. There was no family history of similar defects, no consanguinity, no known exposure to teratogens, and no chromosome abnormality. The retention of Müllerian structures and undervirilization of male genitalia in these cases could be the result of failure in production of adequate amounts of testosterone and Müllerian inhibitory factor at appropriate times in gestation. Because the developing human vagina is at no stage a duplicate structure, a double vagina cannot be the result of arrested genital differentiation. The unusual occurrence of a true double vagina should lead to careful pulmonary and cardiac evaluation.

Abnormalities, Multiple↗

PubMed2004

Surgical reinforcement of support for the vagina in pelvic organ prolapse: concurrent iliococcygeus fascia colpopexy (Inmon technique).

To reinforce the support of the vagina, concurrent use of iliococcygeus fascia colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse. Forty-five women with primary uterine prolapse without stress urinary incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina. Recurrence of vaginal support defects were carefully followed for 15-50 months. Additional iliococcygeus fascia colpopexy did not change with the axis of the vagina obtained by McCall culdeplasty, although it prolonged total operation time by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative vaginal defects in the group undergoing combined procedures and seven recurrent cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The durability of the combined procedures was superior to that of the modified McCall culdeplasty alone by Kaplan-Meier analysis. These results suggest that iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the attachment of the upper part of the vagina but also that of the anterolateral vaginal wall.

Aged↗

PubMed1994

Construction of an artificial vagina with sigmoid colon in vaginal agenesis.

OBJECTIVES: The study of 15 cases of colonic reconstruction for absent vagina. The outcome in cases of reconstruction of an artificial vagina using the colon is evaluated. METHODS: Fifteen female patients with congenital absence of vagina who were evaluated and treated with sigmoid colonic reconstruction at the Korle-Bu Teaching Hospital in Accra, Ghana were studied. RESULTS: This reconstructive method is successful in patients having a functioning vagina without progressive shrinkage or other symptoms. Disfigurement of the thighs and labia are avoided as is the need for active manipulation. CONCLUSION: Sigmoid colonic reconstruction for vaginal agenesis is an acceptable method especially in the developing world.

Adolescent↗

PubMed1986

Biological responses of tamoxifen in the fetal and newborn vagina and uterus of the guinea-pig and in the R-27 mammary cancer cell line.

The biological and morphological responses of tamoxifen were studied in two models: the uterus and vagina of fetal and newborn guinea-pigs: R-27 cells--a mammary cancer cell line (tamoxifen resistant) derived from the MCF-7 cancer cell line. Tamoxifen (TAM) alone or in combination with estradiol (E2) was administered to pregnant (50-52 days of gestation) or to newborn (2-day-old) guinea-pigs for a long period (12 days). TAM alone produced a great trophic effect on the uterus and vagina which was markedly enhanced when TAM was administered together with E2. Histological studies showed that TAM provokes morphological changes in both the endometria and the myometria and this effect was also greater when TAM was administered together with E2. In the fetal uterus and vagina, the ultrastructural studies showed that TAM induces morphological alterations in different cytoplasmic organelles. This effect was much more intense in newborns where TAM provoked a significant vacuolization of the epithelial cells. Concerning progesterone receptor (PR) in the fetal or newborn tissues (uterus or vagina) TAM provoked a less intense effect than those provoked by E2, but TAM did not block the effect provoked by E2. It was observed that [3H]TAM binds specifically to the estrogen receptor (ER) of fetal guinea pig uterus and this complex is partially recognized by a monoclonal antibody which recognizes the activated form of this receptor, supporting the suggestion that the biological action of TAM is mediated by the ER. The biological and ultrastructural effects provoked by TAM (1 X 10(-6) M), estriol (E3)(5 X 10(-8) M) and the combination of TAM + E3 were studied in the R-27 mammary cancer cell line in culture. E3 stimulated the PR content by 7-10 times. However, TAM did not provoke a significant decrease in the concentration of PR, and in the mixture of TAM + E3 the concentration of PR was of the same order as that in E3 treatment. Ultrastructural observations indicate an intense concentration of ribosomes in the pericytoplasmic area after exposure to E3 and with exposure to TAM an increase in vacuoles and a significant enlargement of the size of the mitochondria were observed. It is concluded that TAM in the target tissues of fetal and newborn guinea pigs acts as a real estrogen and in the R-27 mammary cancer cell line TAM does not block the effect provoked by E3, however it does provoke intense ultrastructural modifications.

Animals↗

PubMed2005

Neuropeptide receptor transcripts are expressed in the rat clitoris and oscillate during the estrus cycle in the rat vagina.

Vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and angiotensin 2 are key neuropeptides that innervate the sexual organs. For further understanding of neuropeptide involvement in female sexual function, we investigated peptide receptor mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR) in the rat vagina and clitoris, and alteration during the shift from the proestrus to the estrus phase. VIP, angiotensin 2 and CGRP receptor subtypes transcripts were found to be expressed in the vagina and the clitoris. Significantly increased levels of angiotensin 2 and CGRP receptor subtypes transcripts were observed in the vagina as compared to the clitoris. Significant increases in the expression of the VIP receptor type 2 (VPAC2) mRNA and parallel increases in a novel VIP responsive gene, activity-dependent neuroprotective protein (ADNP) mRNA were detected in the rat vagina during the estrus phase. The expression pattern of neuropeptide receptors in the female sexual organs suggest an intimate involvement of the corresponding neuropeptides in female sexual function.

Animals↗

PubMed1991

Abdominoperitoneal approach to management of the high, short vagina in the adrenogenital syndrome.

We describe a combined transtrigonal, abdominoperineal approach to the surgical management of the female pseudohermaphrodite with the adrenogenital syndrome and a high, short vagina. Most of our patients had undergone previous clitoral reduction surgery and, therefore, clitoral shaft skin was not available for exteriorization of the vagina. Our operation involves partial mobilization of the vagina through an inverted U flap from the perineum followed by detachment from the urogenital sinus from above by splitting the trigone. Exteriorization is accomplished by mobilizing 2 lateral skin flaps from the perineum and joining them with the inverted U flap to reach the vagina. Cosmetic results have been excellent, although anastomotic stenosis occurred in 1 young infant.

Abdomen↗

PubMed1998

Characterization of nitric oxide synthase activity in rabbit uterus and vagina: downregulation by estrogen.

Nitric oxide synthase (NOS) was determined in the soluble (cytosolic) and particulate fractions of rabbit uterus, vagina and cerebellum and the influence of estrogen treatment on NOS activity was studied. NOS in both the cytosolic and particulate fractions was highly calcium dependent. The activity in cytosolic fraction was nearly 4-fold higher than the particulate fractions from all three organs. The concentration of NOS was highest in cerebellum followed by vagina and uterus. Vaginal NOS activity was 3-4-fold higher than the uterine NOS. After a continuous treatment of rabbits for one week with estrogen, cytosolic NOS was reduced by nearly 7 and 4-fold in the uterus and vagina, respectively, whereas there was no significant change in the particulate NOS. Estrogen treatment caused no change in cytosolic or particulate NOS from the cerebellum. Downregulation of cytosolic NOS by estrogen in the estrogen target tissues like uterus and vagina and absence of effect in the cerebellum strongly suggests a physiological significance.

Animals↗

PubMed2000

Mummification of fetal membranes in the bovine vagina: a case report.

Papyraceous, mummified fetal membranes were found in the vagina of a cow at the end of the fourth month after a normal delivery. The uterus and cervix were without any pathological changes. The cow conceived on Day 36 after removal of the mummified fetal membranes upon the second insemination. Apart from the uncommon nature of the case, it proves that after calving the bovine vagina can maintain a sterile environment and that the constrictive mechanism of the vagina can be strong enough to hinder for a long time the discharge of fetal membranes and access of microbes to the vagina.

Animals↗

PubMed1998

Cycle dependent variations in transfer of 133xenon from vagina to uterus in rats.

The possible existence of an oestrus cycle dependent on local transfer of 133xenon from vagina to uterus was investigated in anaesthetized rats. 133Xenon in saline was infused into the vaginal lumen of rats in oestrous (n = 7) and dioestrous (n = 10). The uterus was removed 3 min after the infusion and the radioactivity in the organ counted, after which the remaining radioactivity in vagina was measured. The results showed that the radioactivity increased in all uteri compared with that of the background. The average transfer, expressed as per cent transfer, from vagina in the dioestrous group (5.5%) was significantly higher (P < 0.01, Mann-Whitney) than in the oestrous group (1.4%). The results suggest that the rate of transfer from vagina to uterus depended on the oestrous cycle. Vaginal treatment of women with progesterone for example, may similarly induce high local concentrations in the uterus. Empirically this is already used after in vitro fertilisation, it may also prevent progesterone induced migraine in menopausal women. The possible cycle dependent variations in the transfer in women should be evaluated.

Administration, Intravaginal↗

PubMed1992

The connective tissue sheath of uterus and vagina in the human female fetus.

A morphological study concerning the development and arrangement of the connective tissue surrounding uterus and vagina was performed by investigating epoxy resin impregnated sections through the pelves of 9-37-week-old female fetuses, of newborn children and a three-year-old child. In order to study the histology of the connective tissue in detail paraffin, semithin and ultrathin sections were used. The organization of the pelvic connective tissue in female fetuses can best be studied in middle-aged fetuses (19-28 weeks of gestation). We here report that no supportive ligaments of the uterus are found in fetuses of that age group, but that the connective tissue covering uterus and vagina is part of the connective tissue sheaths of neighbouring structures. The fetal uterus is interposed between dense subperitoneal connective tissue circularly covering the vesico- and rectouterine pouch. Dorsally the subperitoneal tissue of the rectouterine pouch joins the circularly arranged connective tissue of the rectal adventitia. A triangularly-shaped plate of dense connective tissue is situated at each lateral border of the cervix uteri. Dorsally it is continuous with the circularly running fibres of the rectouterine pouch. Whereas the dorsal wall of the vagina is loosely connected with the rectal adventitia, fibrous connective tissue intimately fuses the muscular wall of the vagina with that of the neck of the bladder and of the urethra. No evidence is provided for the existence of smooth muscle cells and elastic material within the connective tissue covering the fetal uterus.

Child, Preschool↗

PubMed2004

Estrogen-independent activation of erbBs signaling and estrogen receptor alpha in the mouse vagina exposed neonatally to diethylstilbestrol.

Growth factors and estrogen receptor (ER) signaling cooperate to play essential roles in cell proliferation, differentiation and tumor progression in mouse reproductive organs. Treatment of neonatal mice with diethylstilbestrol (DES) induces an estrogen-independent persistent proliferation and cornification of the vaginal epithelium, which results in cancerous lesions later in life. However, the mechanisms of the estrogen-dependent and -independent pathways essentially remain unknown. We characterized the expression of epidermal growth factor (EGF)-like growth factors (EGF, transforming growth factor alpha (TGF-alpha), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC), amphiregulin (APR), epiregulin (EPR) and neuregulin (NRG) 1) and erbB receptors (EGF receptor (EGFR), erbB2/neu, erbB3 and erbB4) in the vaginae of mice treated either neonatally (0-4 day) or as adults (55-59 day) with estrogens. EGFR and erbB2 were activated in the vaginal epithelium of mice by estrogen treatment. This activation was also encountered in vaginae from neonatally DES-exposed mice, along with the expression of EGF, TGF-alpha, HB-EGF, BTC, APR, EPR and NRG1. Immunohistochemical analysis indicated that erbB2 was primarily expressed in vaginal epithelium. Finally, we found that serine 118 and 167 located in the AF-1 domain of ERalpha were phosphorylated in these vaginae. AG825, AG1478 or ICI 182,780 administration blocked proliferation of vaginal epithelium induced by neonatal DES exposure. Thus, signal transduction via EGFR and erbB2 could be related to the estrogen-induced vaginal changes and persistent erbBs phosphorylation and sustained expression of EGF-like growth factors, leading to ERalpha activation that may result in cancerous lesions in vaginae from neonatally DES-exposed mice later in life.

Animals↗

PubMed2000

Interferon-gamma up-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and recruits lymphocytes into the vagina of immune mice challenged with herpes simplex virus-2.

Lymphocyte recruitment into tissues involves interactions between adhesion molecules on vascular endothelial cells and corresponding ligands on the lymphocyte surface. In the present study we investigated the expression of four endothelial addressins in the vagina and their possible up-regulation by interferon-gamma (IFN-gamma) in immune mice after vaginal challenge with herpes simplex virus type 2. The adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were minimally expressed in the vagina of non-immune mice with or without vaginal challenge and in immune mice before challenge, but both were up-regulated by IFN-gamma, directly or indirectly, in immune mice after challenge. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was detected in most vaginas but was not up-regulated by IFN-gamma in immune mice after virus challenge. E-selectin was not detected in any vaginas. The results suggest that ICAM-1 and VCAM-1 may be involved in rapid, IFN-gamma-mediated recruitment of lymphocytes to the vaginal mucosal of immune mice after local virus challenge.

Animals↗

PubMed1996

Surgical reconstruction of a high cloacal anomaly with two short vaginas.

We treated a patient with a complex cloacal malformation: a high confluence cloaca and 2 separate short vaginas. At the age of 1 year and 2 months the rectocloacal fistula was closed because of frequent urinary infections, and the vaginas were separated from the wide urogenital sinus and anastomosed to the lower colon. At the age of 2 years and 4 months the lower colon, which had been anastomosed with the 2 vaginas, was pulled down to the perineum to serve as a lower vagina, and the sigmoid colon was pulled through to form a neorectum. She is now 7 years old and goes to school without problems of bowel function or urinary function except that catheterization is done twice a day.

Anus, Imperforate↗

PubMed1986

Pattern of loss of spermatozoa from the vagina of the ewe.

In a series of experiments spermatozoa were inseminated blindly into the vagina of ewes and then recovered at varying times after insemination. Most of the spermatozoa inseminated were lost by drainage through the vulva. The rate of loss was not affected by the motility of spermatozoa or oestrous state of the ewe. Initially after insemination the loss was not rapid with 82% of the insemination 18% of spermatozoa remained and by 12 h 10% remained. Spermatozoa were removed from the vagina during withdrawal of the penis after intromission and the extent of this loss varied between rams and with the volume of semen already in the vagina. Up to half the inseminate was lost in this way when there was 0.5 ml of semen in the vagina but only 11% was lost when the volume of inseminate was 0.1 ml. The unavoidable loss of spermatozoa may influence the quantity available for fertilizing ova.

Animals↗

PubMed2003

Carrageenan formulation prevents macrophage trafficking from vagina: implications for microbicide development.

Considerable evidence suggests that human immunodeficiency virus (HIV)-infected macrophages and/or lymphocytes may mediate sexual transmission of HIV. We and others have previously demonstrated that when vitally stained donor mouse lymphocytes or macrophages are placed in the vaginas of mice, some of the stained cells can later be found in the iliac lymph nodes. The aim of this study was to assess the extent of mononuclear cell trafficking from the vagina and to test the possibility that carrageenan formulation, a sulfated polysaccharide formulation containing 3% PDR98-15 carrageenan (PC-515; FMC Biopolymer, Rockland, ME), a vaginal microbicide, would prevent vaginal transmigration of macrophages. When supravitally stained mouse macrophages and T cells were inoculated into the vagina of recipient mice, discrete numbers of donor cells migrated to the recipient iliac and inguinal lymph nodes and spleen. When recipient mice were preinoculated with the carrageenan formulation, the number of macrophages in lymph nodes and spleen was reduced by >90%. In contrast, a methylcellulose formulation, which is believed to be inactive, did not significantly reduce migration to the lymphoid organs. Our findings suggest that the carrageenan formulation blocks cell trafficking of macrophages from vagina and that blocking does not result from cytotoxicity. Blocking cell trafficking may help to prevent sexual transmission of HIV.

Animals↗

PubMed1987

Influence of carbachol and isoproterenol on myoelectrical activity of the uterus, vagina, and duodenum in the conscious domestic hen.

The influence of intravenous infusion (20 min) of carbachol (CAR) and isoproterenol (IPN) on myoelectrical activity of the uterus, vagina, and duodenum was studied in 6 conscious and unrestrained hens. IPN infusions (1.5, 7.5, and 15 micrograms/hen/min) were performed before oviposition, and CAR infusions (0.5, 1.5, and 5 micrograms/hen/min) were administered after oviposition. CAR infusions resulted in a significant stimulation of myoelectrical activity of the vagina (1.5 and 5 micrograms/min) and the duodenum (5 micrograms/min), and in a significant increase (45 +/- 6%) in heart rate (HR), as compared to control values. These effects were blocked by previous i.v. injections of atropine (0.4 mg/hen). IPN infusions induced a significant inhibition of myoelectrical activity of the middle (7.5 and 15 micrograms/min) and caudal (all doses) uterine segments, of the vagina (7.5 and 15 micrograms/min), and of the duodenum (15 micrograms/min), and a significant tachycardia (39 +/- 14%) as compared to control values. The inhibitory effects of IPN on all organs studied and the stimulatory action on HR were suppressed by propranolol (0.24 mg/hen). The sensitivity of the vagina to both drugs argues for a more active participation of this oviductal part in the mechanism of oviposition.

Animals↗

PubMed2002

Androgens and the development of the vagina.

Today it is generally held that the vagina develops from sinovaginal bulbs and that the lower third of the definitive vagina is derived from the urogenital sinus. Here we show that the entire vagina arises by downward growth of Wolffian and Müllerian ducts, that the sinovaginal bulbs are in fact the caudal ends of the Wolffian ducts, and that vaginal development is under negative control of androgens. We designed a genetic experiment in which the androgen receptor defect in the Tfm mouse was used to examine the effects of androgens. Vaginal development was studied by 3D reconstruction in androgen-treated female embryos and in complete androgen-insensitive littermates. In androgen-treated females, descent of the genital ducts was inhibited, and a vagina formed in androgen-insensitive Tfm embryos as it does in normal females. By immmunohistochemical localization of the androgen receptor in normal mouse embryos, we demonstrated that the androgen receptor was expressed in Wolffian duct and urogenital sinus-derived structures, and was entirely absent in the Müllerian duct derivatives. We conclude that the Wolffian ducts are instrumental in conveying the negative control by androgens on vaginal development. The results are discussed under evolutionary aspects at the transition from marsupial to eutherian mammals.

Androgens↗