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Purposes: To investigate the role of 17β-estrogen in Candida albicans (C. albicans) adhesion on human vaginal epithelial cells in vulvovaginal candidiasis (VVC)., Methods: The vaginal epithelial cell line, VK2/E6E7, was used to study the estrogen-induced molecular events between C. albicans and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation in cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade., Results: A transient activation of ERα and FAK was observed following the stimulation with 1000 nM estrogen for 48 h, as well as the increased average number of C. albicans adhering to each vaginal epithelial cell. Estrogen-induced activation of ERa and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 μM concentration and allowed to act for 12 h. Simultaneously, a decrease in the number of adherent C. albicans was observed. However, this inhibitory effect diminished as the concentration of estrogen increased., Conclusion: FAK and ERα signaling cascades were involved in the early interaction between the vaginal epithelial cells and C. albicans, which appeared to be linked with the enhanced cell adhesion leading to VVC and promoted by a certain concentration of estrogen.

Recurrent vulvovaginal infections (RVVI) has not only become an epidemiological and clinical problem but also include large social and psychological consequences. Understanding the mechanisms of both commensalism and pathogenesis are necessary for the development of efficient diagnosis and treatment strategies for these enigmatic vaginal infections. Through this review, an attempt has been made to analyze vaginal microbiota (VMB) from scratch and to provide an update on its current understanding in relation to health and common RVVI i.e. bacterial vaginosis, vulvovaginal candidiaisis and Trichomoniasis, making the present review first of its kind. For this, potentially relevant studies were retrieved from data sources and critical analysis of the literature was made. Though, culture-independent methods have greatly unfolded the mystery regarding vaginal bacterial microbiome, there are only a few studies regarding the composition and diversity of vaginal mycobiome and different Trichomonas vaginalis strains. This scenario suggests a need of further studies based on comparative genomics of RVVI pathogens to improve our perceptive of RVVI pathogenesis that is still not clear (Fig. 5). Besides this, the review details the rationale for Lactobacilli dominance and changes that occur in healthy VMB throughout a women's life. Moreover, the list of possible agents continues to expand and new species recognised in both health and VVI are updated in this review. The review concludes with the controversies challenging the widely accepted dogma i.e. "VMB dominated with Lactobacilli is healthier than a diverse VMB". These controversies, over the past decade, have complicated the definition of vaginal health and vaginal infections with no definite conclusion. Thus, further studies on newly recognised microbial agents may reveal answers to these controversies. Conversely, VMB of women could be an answer but it is not enough to just look at the microbiology. We have to look at the woman itself, as VMB which is fine for one woman may be troublesome for others. These differences in women's response to the same VMB may be determined by a permutation of behavioural, cultural, genetic and various other anonymous factors, exploration of which may lead to proper definition of vaginal health and disease.

Background: Vaginal candidiasis is common disease affecting women; however, how Candida albicans shift from commensalism towards a pathogenic status remains poorly understood. The present study investigated the vaginal epithelial cell (EC) response dynamics under various conditions., Methods: Healthy women, asymptomatic C. albicans carriers, and symptomatic patients with vaginal candidiasis were enrolled in this study. ECs in vaginal swabs were analyzed with cytofluorimetric analysis for pattern recognition receptors and intracellular signals, with lactate dehydrogenase assay performed for cell damage, and an enzyme-linked immunosorbent assay for cytokine expression., Results: The level of toll-like receptor 4 (TLR4), TLR2, and erythropoietin-producing hepatoma A2 (EphA2) expression was significantly higher in ECs from asymptomatic and symptomatic subjects compared to healthy subjects. Activation of transcription factors, nuclear factor-κB (NF-κB) and c-Fos-p-38, was observed in ECs from symptomatic and asymptomatic pseudohyphae/hyphae carriers but not from the asymptomatic yeast carriers. EC damage was only observed in symptomatic patients., Conclusions: The presence of pseudohyphae/hyphae is required to determine vaginal candidiasis; however, it may be not sufficient to induce the pathologic process associated with neutrophil recruitment and EC damage. This study sheds light on the ambiguous role of the hyphal form during vaginal human commensalism., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The human fungal pathogen Candida albicans is the major etiological agent of vulvovaginal candidiasis (VVC). Despite this fact, other non- albicans Candida (NAC) species have frequently been reported, as well. Despite their presence in the vaginal environment, little is known about their capacities to elicit immune responses classically associated with C. albicans -mediated immunopathology, including neutrophil recruitment and proinflammatory cytokine signaling. Therefore, using a combination of in vitro and in vivo approaches, we undertook a comparative analysis to determine whether a representative panel of NAC species could colonize, induce immunopathological markers, or cause damage at the vaginal mucosa. Using a murine model of VVC, C. albicans was found to induce robust immunopathology (neutrophils and interleukin 1β [IL-1β]) and elicit mucosal damage. However, all the NAC species tested (including C. dubliniensis , C. tropicalis , C. parapsilosis , C. krusei , C. glabrata , and C. auris ) induced significantly less damage and neutrophil recruitment than C. albicans , despite achieving similar early colonization levels. These results largely correlated with a notable lack of ability by the NAC species (including C. dubliniensis and C. tropicalis ) to form hyphae both in vitro and in vivo Furthermore, both C. dubliniensis and C. tropicalis induced significantly less expression of the ECE1 gene encoding candidalysin, a key fungal virulence determinant driving VVC immunopathology. In order to determine the relative capacities of these species to elicit inflammasome-dependent IL-1β release, both wild-type and NLRP3 -/- THP-1 cells were challenged in vitro While most species tested elicited only modest amounts of IL-1β, challenge with C. albicans led to significantly elevated levels that were largely NLRP3 dependent. Collectively, our findings demonstrate that although NAC species are increasingly reported as causative agents of VVC, C. albicans appears to be exceedingly vaginopathogenic, exhibiting robust immunopathology, hypha formation, and candidalysin expression. Thus, this study provides mechanistic insight into why C. albicans is overwhelmingly the major pathogen reported during VVC., (Copyright © 2018 American Society for Microbiology.)

Objective: To characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis., Design: Cross-sectional study., Setting: Genital Infections Ambulatory, Department of Tocogynecology, University of Campinas, Campinas, São Paulo-Brazil., Sample: Twenty-four women were included in this study: eight with vulvovaginal candidiasis, eight with cytolytic vaginosis and eight with no vaginal infections or dysbiosis (control group)., Methods: The lipid profile in vaginal discharge of the different study groups was determined by liquid chromatography-mass spectrometry and further analyzed with MetaboAnalyst 3.0 platform., Main Outcome Measures: Vaginal lipids concentration and its correlation with vulvovaginal candidiasis and cytolytic vaginosis., Results: PCA, PLS-DA and hierarchical clustering analyses indicated 38 potential lipid biomarkers for the different groups, correlating with oxidative stress, inflammation, apoptosis and integrity of the vaginal epithelial tissue. Among these, greater concentrations were found for Glycochenodeoxycholic acid-7-sulfate, O-adipoylcarnitine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group; N-(tetradecanoyl)-sphinganine, DL-PPMP, 1-oleoyl-cyclic phosphatidic, palmitic acid and 5-aminopentanoic acid in the cytolytic vaginosis group; and 1-nonadecanoyl-glycero-3-phosphate, eicosadienoic acid, 1-stearoyl-cyclic-phosphatidic acid, 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphate, formyl 9Z-tetradecenoate and 7Z,10Z-hexadecadienoic acid in the control group., Conclusions: Lipids related to oxidative stress and apoptosis were found in higher concentrations in women with vulvovaginal candidiasis and cytolytic vaginosis, while lipids related to epithelial tissue integrity were more pronounced in the control group. Furthermore, in women with cytolytic vaginosis, we observed higher concentrations of lipids related to bacterial overgrowth., Competing Interests: The authors have declared that no competing interests exist.

Candida spp. are part of the normal vaginal microflora in 20-30% of healthy women. However, if the balance between these yeasts and the host is disturbed, Candida spp. can cause vulvovaginal candidiasis (VVC), with Candida albicans being the major causative agent. Different studies have been performed in order to better understand Candida's dual lifestyle in the vagina. The potential of C. albicans to switch from the yeast cell morphology to its hyphal form is considered a key element in VVC pathogenesis. Candida spp. also express other virulence factors, such as hydrolytic extracellular enzymes and heat shock proteins and can form biofilms., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Histatin5 (Hst-5) is a member of the histatin family of antimicrobial peptides secreted by human parotid and submandibular glands. With the natural antibacterial activity, it plays an important role in the first-line barrier of oral cave against pathogens, especially for the fungal intrusion. In this study, we explored the utility of Hst-5 in the treatment of vulvovaginal candidiasis, a common condition of women of the childbearing age. We used a synthesized Hst-5 over five consecutive days as the topical treatment in a murine model of vulvovaginal candidiasis. According to the fungal colony counts, fungal burden in the vagina lavage dropped remarkably after treatment with Hst-5. Furthermore, cytological analysis of the lavage fluid indicated that the number of cast-off cells including cornified epithelial cells and inflammatory cells also decreased; histological evaluation of the vagina tissue revealed less fungi adhering to the vaginal wall in treated animals than in controls. Combined, these results suggested for the first time the potential utility of Hst-5 as a topical treatment for vulvovaginal candidiasis, uncovering the possibility of exploiting the natural antibiotic peptides in other aspects., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Problem: Autophagy plays an important role in clearance of intracellular pathogens. However, no information is available on its involvement in vaginal infections such as vulvo-vaginal candidiasis (VVC). VVC is intimately associated with the immune status of the human vaginal epithelial cells (VECs). The objective of our study is to decipher if autophagy process is involved during Candida albicans infection of VECs., Methods of Study: In this study, C. albicans infection system was established using human VEC line (VK2/E6E7). Infection-induced change in the expression of autophagy markers like LC3 and LAMP-1 were analyzed by RT-PCR, q-PCR, Western blot, immunofluorescence and transmission electron microscopy (TEM) studies were carried out to ascertain the localization of autophagosomes. Multiplex ELISA was carried out to determine the cytokine profiles., Results: Analysis of LC3 and LAMP-1 expression at mRNA and protein levels at different time points revealed up-regulation of these markers 6 hours post C. albicans infection. LC3 and LAMP-1 puncti were observed in infected VECs after 12 hours. TEM studies showed C. albicans entrapped in autophagosomes. Cytokines-TNF-α and IL-1β were up-regulated in culture supernatants of VECs at 12 hours post-infection., Conclusion: The results suggest that C. albicans invasion led to the activation of autophagy as a host defense mechanism of VECs., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The concept of infertility as a result of asymptomatic microbial colonization of the female reproductive tract has been neglected to date. However, increasing incidence of infertility and advanced research has drawn attention towards this idea. Many of these micro-organisms have been reported to bring about adverse changes in sperm parameters in vitro, but their in vivo potential to cause infertility is still a controversy. The present study was carried out to observe what effect the intravaginal inoculation of sperm-agglutinating Serratia marcescens and sperm-immobilizing Candida albicans had in the reproductive tract and consequently in fertility outcome. When these strains were intravaginally inoculated into female BALB/c mice at 10(4), 10(6) and 10(8) c.f.u. in 20 µl PBS for 10 consecutive days, with mating of mice on day 12, the results showed 100 % decrease in fertility in all groups as compared with control mice receiving PBS alone. Furthermore, no clinical or histopathological changes were observed in the reproductive organs (i.e. ovary, uterus and vagina), suggesting that colonization of the genital tract with sperm-impairing micro-organisms could be a feasible reason for female infertility., (© 2015 The Authors.)

Problem:   The extent of the vaginal immune response is not fully determined. The purpose of this study was to evaluate the vaginal immune cells from women with vulvovaginitis (VV)., Method of Study: A total of 142 volunteers diagnosed with bacterial vaginosis (BV), vulvovaginal candidiasis (VC), and BV associated with VC or normal microflora were sampled to evaluate the immune cells by flow cytometry. The immune cells were obtained by vaginal lavage and labeled with fluorochrome-conjugated monoclonal antibodies to identify neutrophil granulocytes, macrophages, CD4(+) and CD8(+) T lymphocytes, B lymphocytes, and NK lymphocytes., Results: Neutrophil granulocytes were present in 84.6% of samples among the leukocyte populations. Considering samples in which neutrophils were present, the mean percentage of neutrophil granulocytes was significantly higher in women with VC than BV and normal microflora and was significantly lower in women with BV than normal microflora. Macrophages and lymphocytes were present in a lower percentage of samples. The mean percentage of CD4(+) T lymphocytes in vaginal lavages was significantly higher in VC and BV compared with women with normal microflora., Conclusions: Neutrophils were the predominant leukocytes and were associated with VC and inversely with BV. CD4(+) T lymphocytes were associated with both VC and BV., (© 2011 John Wiley & Sons A/S.)

Provoked vestibulodynia, the most common form of vulvodynia (unexplained pain of the vulva), is a prevalent, idiopathic pain disorder associated with a history of recurrent candidiasis (yeast infections). It is characterized by vulvar allodynia (painful hypersensitivity to touch) and hyperinnervation. We tested whether repeated, localized exposure of the vulva to a common fungal pathogen can lead to the development of chronic pain. A subset of female mice subjected to recurrent Candida albicans infection developed mechanical allodynia localized to the vulva. The mice with allodynia also exhibited hyperinnervation with peptidergic nociceptor and sympathetic fibers (as indicated by increased protein gene product 9.5, calcitonin gene-related peptide, and vesicular monoamine transporter 2 immunoreactivity in the vaginal epithelium). Long-lasting behavioral allodynia in a subset of mice was also observed after a single, extended Candida infection, as well as after repeated vulvar (but not hind paw) inflammation induced with zymosan, a mixture of fungal antigens. The hypersensitivity and hyperinnervation were both present at least 3 weeks after the resolution of infection and inflammation. Our data show that infection can cause persistent pain long after its resolution and that recurrent yeast infection replicates important features of human provoked vulvodynia in the mouse.

In this study, we investigated the epidemiological characteristics of VVC among pregnant women. We conducted a prospective survey among 372 pregnant women to investigate the prevalence, clinical forms, etiological agents, and predisposing factors of VVC. In addition, we determined the relationship between vaginal and rectal flora by simultaneously obtaining one high vaginal swab and one rectal swab from each patient using sterile cotton-tipped swabs. Furthermore, we compared the recovery and identification performances of chromID Candida agar to Sabouraud dextrose agar with gentamicin and chloramphenicol. Clinically and mycologically confirmed cases of VVC were detected in 139 (37.4%) and vaginal colonization described in 42 (11.3%) of 372 pregnant women. Rectal cultures were also positive in 98 of the 139 (70.5%) VVC cases. Candida albicans and C. glabrata were identified in vaginal samples in 58.0 versus 19.0% and from rectal samples in 49.0 versus 13.5%, respectively. Increases in gestational week and gravidae were identified to be statistically significant in patients with acute VVC (AVVC) and symptomatic recurrent VVC (RVVC), and asymptomatic RVVC (P = 0.04 and P = 0.03, respectively). In the laboratory diagnosis of VVC, specifically tailored chromogenic media are reliable tools for both the recovery and rapid identification of common Candida spp., particularly C. albicans, as well as for the detection of polyfungal populations in vaginal samples (P > 0.05). In addition, rectal colonization is a common finding in cases of AVVC and symptomatic-RVVC cases and corresponds well with the presence of the same yeast species in the vagina.

In order to evaluate an effective administration method of essential oils for vaginal candidiasis, efficacy of vaginal application of essential oils against murine experimental candidiasis was investigated. The effect on vaginal inflammation and Candida growth form was also studied. Vaginal candidiasis was established by intravaginal infection of C. albicans to estradiol-treated mice. These mice intravaginally received essential oils such as geranium and tea tree singly or in combination with vaginal washing. Vaginal administration of clotrimazole significantly decreased the number of viable C. albicans cells in the vaginal cavity by itself. In contrast, these essential oils did not lower the cell number. When application of geranium oil or geraniol was combined with vaginal washing, the cell number was decreased significantly. The myeloperoxidase activity assay exhibited the possibility that essential oils worked not only to reduce the viable cell number of C. albicans, but also to improve vaginal inflammation. The smear of vaginal washing suspension suggested that more yeast-form cells appeared in vaginal smears of these oil-treated mice than in control mice. In vitro study showed that a very low concentration (25 microg/ml) of geranium oil and geraniol inhibited mycelial growth, but not yeast growth. Based on these findings, it is estimated that vaginal application of geranium oil or its main component, geraniol, suppressed Candida cell growth in the vagina and its local inflammation when combined with vaginal washing.

Antibody variable domains (domain antibodies [DAbs]) are genetically engineered antibody fragments that include individual heavy-chain (VH) or kappa-chain (Vkappa) variable domains and lack the Fc region. Human DAbs against the 65-kDa mannoprotein (MP65) or the secretory aspartyl proteinase (SAP)-2 of Candida albicans (monospecific DAbs) or against both fungal antigens (heterodimeric, bispecific DAbs) were generated from phage expression libraries. Both monospecific and bispecific DAbs inhibited fungus adherence to the epithelial cells of rat vagina and accelerated the clearance of vaginal infection with the fungus. When heterodimeric DAbs were used, the clearance of infection was at least equivalent to treatment with fluconazole. The in vivo protective effects of DAbs were demonstrated by both pre- and postchallenge schedules of DAb administration and with both fluconazole-susceptible and fluconazole-resistant strains of C. albicans. This is the first demonstration that human DAbs lacking the Fc constituent can efficiently control an infection and can act largely by inhibiting adherence.

Objective: To evaluate the possibilities of a cervical cytology screening program and the importance of lifestyle parameters in women living in rural Vietnam., Study Design: Screening took place in Quangninh province in the north of Vietnam. From 700 women screened for the first time, smears were prepared and read by a cytotechnologist. The number of children and abortions (some women having had 10 abortions) allowed us to study the relationship of these life-style parameters with disturbed vaginal ecology (defined as the presence of Candida, trichomonads or cocci in the smear)., Results: The smears from farmers showed the greatest ecologic disturbances in vaginal flora. Water supply turned out to be important for coccoid overgrowth. Scores for both fungal infection and coccoid overgrowth were related to profession. Candidosis proved to be very prominent in cytologically negative smears: the organisms were found (often in abundance) in 95 of 661 negative smears but were absent from cytologically positive smears., Conclusion: Since only two cases of CIN 3 were found and no cases of invasive carcinoma, cervical screening for cancer ought not to be the first priority for rural Vietnam.

Vaginal Candida glabrata infections have increased significantly in recent years and are particularly common in women with uncontrolled diabetes mellitus. Efforts to understand the pathogenesis and treatment of this infection have been hindered by the lack of experimental animal models. Before onset of hyperglycemia, nonobese diabetic (NOD) mice inoculated intravaginally with clinical C. glabrata isolates were shown to support high vaginal titers of C. glabrata for > 14 days with evidence for superficial invasion of vaginal epithelial tissue. In contrast, congenic diabetic-resistant mice and mice susceptible to Candida albicans infections were significantly less susceptible to vaginal infection by C. glabrata, suggesting a potential link between the susceptibility of NOD mice to diabetes and their susceptibility to vaginal C. glabrata infections. This animal model of C. glabrata vaginitis provides a means to study the genetics and pathogenesis of C. glabrata infections and to evaluate the efficacy of antimycotic agents against C. glabrata.

Objectives: To compare the clinical usefulness of culture and wet smear microscopy in low-symptomatic vulvovaginal candidosis (VVC) diagnosis., Study Design: Women attending for contraceptive advice were screened for vaginal yeast fungi by culture and wet smear microscopy. A positive culture was found in 130 (13.2%) of the 983 women studied, while a positive wet smear was found in 133 (13.9%). In 40 (30%) of these women both the culture and wet smear was positive., Results: The methods were equally sensitive in predicting symptoms of VVC, such as pruritus, smarting and burning pain, as well as for dyspareunia (35% vs. 36%), but wet smear microscopy was more sensitive in predicting signs of VVC, such as erythema and abnormal discharge (52% vs. 34%). The highest sensitivity was reached when both methods were positive (60% for symptoms, 75% for signs). There was no quantitative correlation between number of Candida colonies on culture on the one hand and symptoms, signs or a positive wet smear on the other hand. Using four parameters as a diagnostic battery for VVC, the two methods complemented each other. The correlation between symptoms and/or signs for wet smear was high than for culture., Conclusion: Wet smear microscopy of vaginal secretion, along with signs found at examination, should be the first-line test in the diagnosis of VVC. Culture must, however, be used when there is a clinical suspicion of VVC and a negative wet smear, or when speciation or antibiotic susceptibility tests of isolates are required.

Exudates from the vagina and uterine cervix of ten patients suffering from genital candidiasis (Candida albicans) were studied with transmission and scanning electron microscopy and with histochemical techniques in order to find the precise location of the Candida infection and to examine the relationship between the vaginal and cervical cells and the infecting yeasts. It was found that Candida species can penetrate, invade, develop and proliferate within the deep layers of intact cells of the cervix and vaginal mucosal epithelium. The presence of mucopolysaccharides in the glycoproteinaceous coat of blastospores and pseudohyphae was demonstrated both outside and within squamous epithelial cells. The importance of the integrity of the glycoprotein coat during the pathogenesis of human infection with C. albicans is therefore emphasized. Furthermore, the histoinvasive yeast apparently produced cytolytic enzymes during its growth within the human vaginal and cervical mucosal epithelium. The intracellular growth of Candida organisms may represent a protective mechanism of the fungus against the host and a manner of resistance to antimycotic therapy.

Histological changes of vaginal mucosa and portio vaginalis are described in women of reproductive age suffering from candidosis. The epithelial surface is covered with adherent masses composed of desquamated and destroyed epithelial cells and leukocytes impregnated with proteins and penetrated by pseudomycelium. The outer epithelial layers are characterized by dystrophic and necrobiotic changes, desquamation, formation of fissures and small cavities. Pseudomycelium penetrates 4 to 6 layers of the epithelium. The barrier between the invading pathogen and the blood vessels of the lamina propria papillae in some sites is only 5-6 flattened epithelial cells thick. In the basal layer, high mitotic activity is noted. Lamina propria contains lympho-plasmocytic infiltrates.

Pathomorphogenesis of candidal colpitis was studied using the murine model with induced oestrus. After intravaginal inoculation, the adherence of pathogen to the mucosal surface of vagina is noted which is followed by its invasion into superficial and deep epithelial layers with the formation of germ tubes and pseudomycelium. The fungal cells are eliminated by the epithelial desquamation and by leukocytes migrating into the epithelium and forming intraepithelial abscesses. The sanation of mucosa is achieved by the sequestration of infected epithelium from the non-infected one. Tissue reactions appear to be in close correlation with the activity of pathogen during all the phases of mycotic process.

The scanning electron microscopic pattern of the development of yeasts of Candida albicans on the vaginal mucosa of mice in oestral phase, was studied in four consecutive infections performed at 30 d intervals. The findings were practically identical following the 1st and 2nd infections, evidencing a progressive mycelial development starting from 12 to 72 h after inoculation with C. albicans yeasts. In the 3rd and 4th infections the mycelial tufts appeared extremely reduced in number and size, although there was an acceleration in the early evolutive phases and the filamentation process had already started 6 h after infection. It can be concluded that, after successive infections with C. albicans, mouse vaginal mucous membrane develops a local state of resistance evidenced by the decrease in mycelial tufts. The possible causes of the early onset of the filamentation process are discussed.

The vaginal epithelium of randomly bred albino rats normally does not contain yeast. This study demonstrated that estrogen-primed, castrated rats could be colonized by Candida albicans following intravaginal challenge, whereas rats not treated with estrogen remained resistant to colonization. The bacteriologic conditions of the vagina were also studied in yeast-colonized and non-yeast-colonized rats. No evidence of bacterial interference with yeast colonization was obtained from this study since the vaginal flora of the estrogen-treated, yeast-colonized rats was more abundant and diverse than that of the non-estrogen-treated rats, which were resistant to yeast colonization. Scanning electron microscopy of the vaginal epithelium of yeast-colonized rats showed that C. albicans entered the mycelial phase during colonization of the vagina. It also appeared that the mycelia penetrate the cornified vaginal epithelial cells.