Recent Advances in Understanding the Microbiology of the Female Reproductive Tract and the Causes of Premature Birth

Data derived from molecular microbiological investigations of the human vagina have led to the discovery of resident bacterial communities that exhibit marked differences in terms of species composition. All undergo dynamic changes that are likely due to intrinsic host and behavioral factors. Similar types of bacteria have been found in both amniotic fluid and the vagina, suggesting a potential route of colonization. Given that not all of the species involved in intrauterine infections are readily cultivated, it is important that culture-independent methods of analysis must be used to understand the etiology of these infections. Further research is needed to establish whether an ascending pathway from the vagina to the amniotic cavity enables the development of intrauterine infections.

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Uterine microbiome—low biomass and high expectations†

Biology of Reproduction ◽

10.1093/biolre/ioy257 ◽

2018 ◽

Vol 101 (6) ◽

pp. 1102-1114 ◽

Cited By ~ 3

Author(s):

Iolanda Garcia-Grau ◽

Carlos Simon ◽

Inmaculada Moreno

Keyword(s):

Bacterial Communities ◽

Sampling Method ◽

Reproductive Tract ◽

Female Reproductive Tract ◽

High Expectations ◽

Downstream Analysis ◽

Uterine Diseases ◽

Human Fetal Development ◽

Infertile Patients

AbstractThe existence of different bacterial communities throughout the female reproductive tract has challenged the traditional view of human fetal development as a sterile event. There is still no consensus on what physiological microbiota exists in the upper reproductive tract of the vast majority of women who are not in periods of infection or pregnancy, and the role of bacteria that colonize the upper reproductive tract in uterine diseases or pregnancy outcomes is not well established. Despite published studies and advances in uterine microbiome sequencing, some study aspects—such as study design, sampling method, DNA extraction, sequencing methods, downstream analysis, and assignment of taxa—have not yet been improved and standardized. It is time to further investigate the uterine microbiome to increase our understanding of the female reproductive tract and to develop more personalized reproductive therapies, highlighting the potential importance of using microbiological assessment in infertile patients.

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In ovo microbial communities: a potential mechanism for the initial acquisition of gut microbiota among oviparous birds and lizards

Biology Letters ◽

10.1098/rsbl.2018.0225 ◽

2018 ◽

Vol 14 (7) ◽

pp. 20180225 ◽

Cited By ~ 12

Author(s):

Brian K. Trevelline ◽

Kirsty J. MacLeod ◽

Sarah A. Knutie ◽

Tracy Langkilde ◽

Kevin D. Kohl

Keyword(s):

Gut Microbiota ◽

Microbial Communities ◽

Bacterial Communities ◽

Reproductive Tract ◽

Egg Yolk ◽

Fungal Communities ◽

In Ovo ◽

Physiological Processes ◽

Initial Acquisition ◽

Culture Independent

Vertebrate gut microbiota mediate critical physiological processes known to affect host fitness, but the mechanisms that expose wildlife to pioneer members of this important microbial community are not well understood. For example, oviparous vertebrates are thought to acquire gut microbiota through post-natal exposure to the external environment, but recent evidence from placental mammals suggests that the vertebrate reproductive tract harbours microbiota that may inoculate offspring in utero . These findings suggest that oviparous vertebrates may be capable of acquiring pioneer microbiota in ovo , but this phenomenon remains unexplored. To fill this knowledge gap, we used culture-independent inventories to determine if the eggs of wild birds and lizards harboured in ovo microbial communities. Our approach revealed distinct in ovo bacterial communities, but fungal communities were indistinguishable from controls. Further, lizard eggs from the same clutch had bacterial community structures that were more similar to each other than to unrelated individuals. These results suggest that oviparous vertebrates may acquire maternal microbiota in ovo , possibly through the inoculation of egg yolk prior to shelling. Therefore, this study may provide a first glimpse of a phenomenon with substantial implications for our understanding of the ecological and evolutionary factors shaping gut microbial communities.

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Is the role of human female reproductive tract microbiota underestimated?

Beneficial Microbes ◽

10.3920/bm2015.0174 ◽

2017 ◽

Vol 8 (3) ◽

pp. 327-343 ◽

Cited By ~ 12

Author(s):

D. Kamińska ◽

M. Gajecka

Keyword(s):

Reproductive Tract ◽

Bacterial Species ◽

Bacterial Community Composition ◽

Intrauterine Infection ◽

Extensive Study ◽

Female Reproductive Tract ◽

Foetal Development ◽

Culture Independent ◽

The Impact

An issue that is currently undergoing extensive study is the influence of human vaginal microbiota (VMB) on the health status of women and their neonates. Healthy women are mainly colonised with lactobacilli such as Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners; however, other bacteria may be elements of the VMB, particularly in women with bacterial vaginosis. The implementation of culture-independent molecular methods in VMB characterisation, especially next-generation sequencing, have provided new information regarding bacterial diversity in the vagina, revealing a large number of novel, fastidious, and/or uncultivated bacterial species. These molecular studies have contributed new insights regarding the role of bacterial community composition. In this study, we discuss recent findings regarding the reproductive tract microbiome. Not only bacteria but also viruses and fungi constitute important components of the reproductive tract microbiome. We focus on aspects related to the impact of the maternal microbiome on foetal development, as well as the establishment of the neonatal microbiomes, including the placenta microbiome, and the haematogenous source of intrauterine infection. We also discuss whether the role of the vaginal microbiome is currently understood and appreciated.

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Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche

10.1101/2021.07.07.447795 ◽

2021 ◽

Author(s):

Karen V. Lithgow ◽

Vienna C.H. Buchholz ◽

Emily Ku ◽

Shaelen Konschuh ◽

Ana D'Aubeterre ◽

...

Keyword(s):

Extracellular Matrix ◽

Reproductive Tract ◽

Type I Collagen ◽

Structural Integrity ◽

Opportunistic Pathogen ◽

Cysteine Proteases ◽

Female Reproductive Tract ◽

Cloning And Expression ◽

Type I ◽

Human Vagina

Porphyromonas asaccahrolytica and Porphyromonas uenonis are frequently isolated from the human vagina and are linked to bacterial vaginosis and preterm labour. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. Given their phylogenetic relatedness, we hypothesized that vaginal Porphyromonas species possess gingipain-like protease activity targeting host extracellular matrix in the female reproductive tract. In this study, we demonstrate that vaginal Porphyromonas species degrade type I collagen (cervix), type IV collagen (chorioamnion/placenta), and fibrinogen, but not through the activity of gingipain orthologs. Bioinformatic queries identified five candidate collagenases in each species, including serine, cysteine and metalloproteases, with signal peptides directing them to the extracellular environment. Inhibition assays revealed both species secrete metalloproteases that degrade collagen and casein, while P. asaccharolytica also secretes a metalloprotease that degrades fibrinogen. Phylogenetic analysis of the predicted collagen-degrading metalloprotease revealed an orthologous relationship with the P. gingivalis endopeptidase PepO. Cloning and expression of P. asaccharolytica PepO confirmed this protein's collagenase and caseinase activities, which have not previously been attributed to PepO homologs in other bacteria. Altogether, this description of the first known virulence factor in Porphyromonas species colonizing the human vagina sheds light on their potential to alter the structural integrity and homeostasis of reproductive tissues.

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The female urinary microbiota in relation to the reproductive tract microbiota

Gigabyte ◽

10.46471/gigabyte.9 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Chen Chen ◽

Lilan Hao ◽

Weixia Wei ◽

Fei Li ◽

Liju Song ◽

...

Keyword(s):

Microbial Communities ◽

Bacterial Communities ◽

Reproductive Tract ◽

Uterine Cavity ◽

Detailed Comparison ◽

Female Reproductive Tract ◽

Reproductive Age ◽

Rrna Gene ◽

Urogenital System ◽

Urinary Microbiota

Human urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. Potential links between female urine and reproductive tract microbial communities is currently not clear. Here, we collected urine samples from 147 Chinese women of reproductive age and explored the nature of colonization by 16S rRNA gene amplicon sequencing, quantitative real-time PCR, and live bacteria culture. To demonstrate the utility of this approach, the intra-individual Spearman’s correlation was used to explore the relationship between urine and multiple sites of the female reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Streptococcus-dominated, Lactobacillus-dominated, and diverse type were the three most common urinary bacterial community types in the cohort. Detailed comparison of the urinary microbiota with multiple sites of the female reproductive tract microbiota demonstrated that the urinary microbiota were more similar to the microbiota in the cervix and uterine cavity than to those of the vagina in the same women. Our data demonstrate the potential connectivity among microbiota in the female urogenital system and provide insight and resources for exploring diseases of the urethra and genital tract.

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Effect of Contraceptive Steroids on the Endometrium of Guinea Pig: SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080766 ◽

1977 ◽

Vol 35 ◽

pp. 668-669

Author(s):

Mai M. Said ◽

Ramesh K. Nayak ◽

Randall E. McCoy

Keyword(s):

Guinea Pig ◽

Reproductive Tract ◽

Three Dimensional ◽

Female Reproductive Tract ◽

Human Female ◽

Surface Ultrastructure ◽

Transmission Electron ◽

Sem Study ◽

Uterine Mucosa ◽

Group 1

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.

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Surface ultrastructure of danazol treated rat endometrium: A SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007641x ◽

1983 ◽

Vol 41 ◽

pp. 556-557

Author(s):

R.P. Apkarian ◽

J.S. Sanfilippo

Keyword(s):

Cross Sections ◽

Reproductive Tract ◽

Preliminary Investigation ◽

Breast Disease ◽

Distal Segment ◽

Uterine Horn ◽

Female Reproductive Tract ◽

Ultrastructural Changes ◽

Cycle Phase ◽

Sprague Dawley

The synthetic androgen danazol, is an isoxazol derivative of ethisterone. It is utilized in the treatment of endometriosis, fibrocystic breast disease, and has a potential use as a contraceptive. A study was designed to evaluate the ultrastructural changes associated with danazol therapy in a rat model. The preliminary investigation of the distal segment of the rat uterine horn was undertaken as part of a larger study intended to elucidate the effects of danazol on the female reproductive tract.Cross-sections (2-3 mm in length) of the distal segment of the uterine horn from sixteen Sprague-Dawley rats were prepared for SEM. Ten rats in estrus served as controls and six danazol treated rats were noted to have alterations of the estrus cycle i.e. a lag in cycle phase or noncycling patterns. Specimens were fixed in 3% glutaraldehyde in 0.05M phosphate buffer containing CaCl2 at pH 7.0-7.4 and chilled to 4°C. After a brief wash in distilled water, specimens were passed through a graded series of ethanol, critical point dryed in CO2 from absolute ethanol, and coated with 6nm Au. Observations were made with an IS1-40 SEM operated at 15kV.

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The application of electron microscopy to diagnosis in gynecologic neoplasms and tumor-like conditions

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100110787 ◽

1984 ◽

Vol 42 ◽

pp. 102-105

Author(s):

Lawrence M. Roth

Keyword(s):

Electron Microscopy ◽

Reproductive Tract ◽

Malignant Tumors ◽

Frozen Section ◽

Cost Effective ◽

Female Reproductive Tract ◽

Ultrastructural Examination ◽

Specific Diagnosis ◽

Potential Value ◽

Gynecologic Neoplasms

The female reproductive tract may be the site of a wide variety of benign and malignant tumors, as well as non-neoplastic tumor-like conditions, most of which can be diagnosed by light microscopic examination including special stains and more recently immunoperoxidase techniques. Nevertheless there are situations where ultrastructural examination can contribute substantially to an accurate and specific diagnosis. It is my opinion that electron microscopy can be of greatest benefit and is most cost effective when applied in conjunction with other methodologies. Thus, I have developed an approach which has proved useful for me and may have benefit for others. In cases where it is deemed of potential value, glutaraldehyde-fixed material is obtained at the time of frozen section or otherwise at operation. Coordination with the gynecologic oncologist is required in the latter situation. This material is processed and blocked and is available if a future need arises.

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