Exogenous Reproductive Hormones nor Candida albicans Colonization Alter the Near Neutral Mouse Vaginal pH

Abstract

While human vaginal pH in childbearing aged women is conclusively acidic, the mouse vaginal pH is reported as being near neutral. However, this information appears to be somewhat anecdotal with respect to vulvovaginal candidiasis as such claims in the literature frequently lack citations of studies that specifically address this physiological factor. Given the disparate pH between mice and humans, the role of exogenous hormones and colonization by the fungal pathogen Candida albicans in shaping vaginal pH was assessed. Use of a convenient modified vaginal lavage technique with the pH indicator dye phenol red demonstrated that indeed vaginal pH was near neutral (7.2 ± 0.24) and was not altered by delivery of progesterone or estrogen in C57BL/6 mice. These trends were conserved in DBA/2 and CD-1 mouse backgrounds commonly used in the mouse model of vaginitis. It was also determined that vaginal colonization with C. albicans did not alter the globally neutral vaginal pH over the course of one week. Construction and validation of a C. albicans reporter strain expressing GFPy driven by the pH-responsive PHR1 promoter confirmed that the murine vaginal pH to be at least ≥ 6.0. Collectively, our data convincingly demonstrate a stable and conserved near neutrality of the mouse vaginal pH during vulvovaginal candidiasis and should serve as a definitive source for future reference. Implications and rationale for disparate pH in this model system are also discussed.

A variant ECE1 allele contributes to reduced pathogenicity of Candida albicans during vulvovaginal candidiasis

“…While the mouse model of VVC has been an indispensable tool to dissect host immune mechanisms associated with disease, disparate microbiological, physiological, and biochemical landscapes of the vaginal tract exist between mouse and human. One notable difference is the near neutral vaginal pH of mice (pH 6.5-7) which contrasts with a much more acidic vaginal environment observed in women (pH 3.5-5.0) [27]. Acidic pH is known to impair C. albicans hyphal growth and thus logically also ECE1 expression [28].…”

“…Amplicons were digested with SalI and MluI prior to ligation into SalI +MluI digested pKE4 [39]. In order to generate a plasmid harboring the SC5314 ECE1 promoter, vector pKE4-GFPy was digested with StuI and SalI and a similarly digested PCR product generated using primers ECE1Pr3k-F-StuI and PrECE1-R-SalI cloned into that site to yield plasmid PrECE1-GFPy [27]. In order to generate ECE1 peptide swap strains driven by a common SC5314 ECE1 promoter, gBlocks (Integrated DNA Technologies) were cloned into vector PrECE1-GFPy by digestion with SalI and MluI to replace the GFPy coding sequence.…”

Protamine Sulfate Is a Potent Inhibitor of Human Papillomavirus InfectionIn VitroandIn Vivo

“…The human vaginal tract typically maintains an acidic pH, compared to the more neutral pH of mice ( 60 , 61 ). To evaluate PS activity under more human-relevant conditions, we tested PS function in vitro at a pH of 4.5, which is considered normal for premenopausal women ( 61 ).…”

Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells

“…44 Furthermore, both pH and the microbiome of human and mouse vaginas differ. [45][46][47] Since trichomoniasis is also understood to be an ecological disease, where bacterial flora present during infection contribute to pathogenesis, [48][49][50] models that can re-capitulate the polymicrobial environment are more desirable for understanding inflammation. Considerable advances have been recently made in establishing in vitro models that re-capitulate Tv interactions with the human vaginal ectocervical cells [51][52][53] and prototypic microflora of the human cervicovaginal microbiome.…”

“…Even in studies where researchers were able to infect the vagina of mice with Tv, immunosuppressants were required to maintain infection, making this an undesirable model for studies of immunity 44 . Furthermore, both pH and the microbiome of human and mouse vaginas differ 45–47 . Since trichomoniasis is also understood to be an ecological disease, where bacterial flora present during infection contribute to pathogenesis, 48–50 models that can re‐capitulate the polymicrobial environment are more desirable for understanding inflammation.…”