Project description:Leptotrichia amnionii, a recently described, very fastidious, gram-negative anaerobic bacterium, is an opportunistic pathogen of the female urogenital tract. We report a case of second-trimester abortion in a patient with chorioamnionitis and L. amnionii bacteremia and a case of renal abscess in a female 5 weeks postpartum.
Project description:Leptotrichia amnionii is an organism that rarely causes female genital tract infection. We describe a case of a male patient with arthritis on the left knee joint due to this organism.
Project description:Mitogen-activated protein 3 kinase 1 (MAP3K1) has a plethora of cell type-specific functions not yet fully understood. Herein, we describe a role for MAP3K1 in female reproductive tract (FRT) development. MAP3K1 kinase domain-deficient female mice exhibited an imperforate vagina, labor failure and infertility. These defects corresponded with shunted Müllerian ducts (MDs), the embryonic precursors of FRT, that manifested as a contorted caudal vagina and abrogated vaginal-urogenital sinus fusion in neonates. The MAP3K1 kinase domain is required for optimal activation of the Jun-N-terminal kinase (JNK) and cell polarity in the MD epithelium, and for upregulation of WNT signaling in the mesenchyme surrounding the caudal MD. The MAP3K1-deficient epithelial cells and MD epithelium had reduced expression of WNT7B ligands. Correspondingly, conditioned media derived from MAP3K1-competent, but not -deficient, epithelial cells activated a TCF/Lef-luciferase reporter in fibroblasts. These observations indicate that MAP3K1 regulates MD caudal elongation and FRT development, in part through the induction of paracrine factors in the epithelium that trans-activate WNT signaling in the mesenchyme.
Project description:We report three cases of delivery and postpartum bacteremia due to unusual anaerobic bacteria in healthy young women. Leptotrichia amnionii bacteremia occurred during delivery in two mothers and was associated with fetal distress during labor. Conversely, Sneathia sanguinegens bacteremia occurred postpartum, 2 days after delivery, without consequence for the neonate.
Project description:We present a detailed review of the embryonic and fetal development of the human female reproductive tract utilizing specimens from the 5th through the 22nd gestational week. Hematoxylin and eosin (H&E) as well as immunohistochemical stains were used to study the development of the human uterine tube, endometrium, myometrium, uterine cervix and vagina. Our study revisits and updates the classical reports of Koff (1933) and Bulmer (1957) and presents new data on development of human vaginal epithelium. Koff proposed that the upper 4/5ths of the vagina is derived from Müllerian epithelium and the lower 1/5th derived from urogenital sinus epithelium, while Bulmer proposed that vaginal epithelium derives solely from urogenital sinus epithelium. These conclusions were based entirely upon H&E stained sections. A central player in human vaginal epithelial development is the solid vaginal plate, which arises from the uterovaginal canal (fused Müllerian ducts) cranially and squamous epithelium of urogenital sinus caudally. Since Müllerian and urogenital sinus epithelium cannot be unequivocally identified in H&E stained sections, we used immunostaining for PAX2 (reactive with Müllerian epithelium) and FOXA1 (reactive with urogenital sinus epithelium). By this technique, the PAX2/FOXA1 boundary was located at the extreme caudal aspect of the vaginal plate at 12 weeks. During the ensuing weeks, the PAX2/FOXA1 boundary progressively extended cranially such that by 21 weeks the entire vaginal epithelium was FOXA1-reactive and PAX2-negative. This observation supports Bulmer's proposal that human vaginal epithelium derives solely from urogenital sinus epithelium. Clearly, the development of the human vagina is far more complex than previously envisioned and appears to be distinctly different in many respects from mouse vaginal development.
Project description:BackgroundThe human uterus is traditionally believed to be sterile, while the vaginal microbiota plays an important role in fending off pathogens. Emerging evidence demonstrates the presence of bacteria beyond the vagina. However, a microbiome-wide metagenomic analysis characterizing the diverse microbial communities has been lacking.ResultsWe performed shotgun-sequencing of 52 samples from the cervical canal and the peritoneal fluid of Chinese women of reproductive age using the Illumina platform. Direct annotation of sequencing reads identified the taxonomy of bacteria, archaea, fungi and viruses, confirming and extending the results from our previous study. We replicated our previous findings in another 24 samples from the vagina, the cervical canal, the uterus and the peritoneal fluid using the BGISEQ-500 platform revealing that microorganisms in the samples from the same individuals were largely shared in the entire reproductive tract. Human sequences made up more than 99% of the 20GB raw data. After filtering, vaginal microorganisms were well covered in the generated reproductive tract gene catalogue, while the more diverse upper reproductive tract microbiota would require greater depth of sequencing and more samples to meet the full coverage scale.ConclusionsWe provide novel detailed data on the microbial composition of a largely unchartered body site, the female reproductive tract. Our results indicated the presence of an intra-individual continuum of microorganisms that gradually changed from the vagina to the peritoneal fluid. This study also provides a framework for understanding the implications of the composition and functional potential of the distinct microbial ecosystems of the female reproductive tract in relation to health and disease.
Project description:A novel bacterium was isolated and characterized from the amniotic fluid of a woman who experienced intrauterine fetal demise in the second trimester of pregnancy. The bacterium was a slow-growing, gram-negative anaerobic coccobacillus belonging to the genus LEPTOTRICHIA: Unlike Leptotrichia sanguinegens, the isolate did not grow in chopped-meat glucose broth or on sheep blood agar upon subculturing. The isolate was characterized by sequencing and analyzing its 16S rRNA gene. The 1,493-bp 16S ribosomal DNA sequence had only 96% homology with L. sanguinegens. Several phylogenetic analyses indicated that L. amnionii is a distinct species and most closely related to L. sanguiegens.
Project description:In order to better understand the female reproductive tract (FRT) we conducted a systematic, comprehensive investigation of the FRT in a tssue-specific manner at three time points relative to mating. By characterizing the transcriptional relationships among discrete FRT tissues across time we advance the understanding of the molecular genetics of FRT functions.
Project description:Interferon ε (IFNε), a unique type I IFN, is thought to protect the host against sexually transmitted infections. Unlike conventional type I IFNs (e.g., IFNα/β), whose expression is undetectable at baseline, IFNε expression is detectable in the epithelium of mucosal tissues, particularly the female reproductive tract (FRT). We found that IFNε expression was not limited to epithelial cells at the FRT. Importantly, in contrast to previous reports, IFNε expression in plasmacytoid dendritic cells and primary cervical epithelial cells was induced by viral infection and by activation of TLR3 or 4 in PBMCs. Induction of IFNε mRNAs was also found in cervicovaginal tissues (CVT) of Zika virus (ZIKV)-infected mice. Mice with IFNε deficiency (Ifnε-/-) did not have impaired induction of interferon-stimulated genes except IFNl, but had altered epithelial and collagen structure in the CVT. Ifnε-/- mice exhibited increased susceptibility to ZIKV infection via an intravaginal route but not via a subcutaneous route, indicating that the protective effect of IFNe was specific to the FRT. Infected Ifnε-/- mice had higher and more sustained viral loads than infected wild-type (WT) mice. Detection of ZIKV infection by single molecule in situ hybridization confirmed that virus spread faster in Ifnε-/- mice than in WT mice. Recombinant murine IFNε protected Ifnar1-/- mice against ZIKV infection when administered through an intravaginal route but not when administered through a subcutaneous route, indicating that the specific role of IFNe at the FRT is independent of IFNAR1 signaling. Our findings indicate that IFNε mediates a novel FRT-specific protective effect on mucosal immunity that limits Zika virus spread.
Project description:Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Chlamydia Despite robust establishment of localized memory lymphocytes within the FRT, naïve mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting Chlamydia infection via the vaginal route. Blocking the rapid mobilization of circulating memory CD4 T cells to the FRT inhibited this protective response. These data demonstrate that secondary protection in the FRT can occur in the complete absence of tissue-resident immune cells. The ability to confer robust protection to barrier tissues via circulating immune memory provides an unexpected opportunity for vaccine development against infections of the FRT.