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APMIS : Acta Pathologica,... Feb 2023Miscarriage is one of the main causes of reproductive loss, which can lead to a number of physical and psychological complications and other long-term consequences.... (Review)
Review
Miscarriage is one of the main causes of reproductive loss, which can lead to a number of physical and psychological complications and other long-term consequences. However, the role of vaginal and uterine microbiome in such complications is poorly understood. To review the published data on the function of the female reproductive tract microbiome in the pathogenesis of early miscarriages. The articles published over the past 20 years and deposited in PubMed, Google Academy, Scopus, Elibrary, ResearchGate, and EBSCO databases were analyzed. The review presents new data on the impact of the vaginal and uterine microbiome on the local immunity, including defense against sexually transmitted infections, and its association with other factors of miscarriages. The studies on the microbiome of non-pregnant women with recurrent miscarriages in the anamnesis, patients undergoing IVF, and pregnant women with miscarriages, as well as new directions in the microbiome research are discussed. The majority of studies have demonstrated that the dominant species of the vaginal and uterine microbiome in patients with early miscarriages are non-Lactobacillus bacteria. As many of these bacteria have not previously been detected by cultural studies and their role in obstetric complications is not well defined, further research on the female reproductive tract microbiome, including the microbiome of the cervix uteri, is needed to develop new approaches for the prognosis and prevention of miscarriages.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Microbiota; Prognosis; Bacteria; Vagina
PubMed: 36511842
DOI: 10.1111/apm.13288 -
MSphere Dec 2020Dominance of species in vaginal communities is a hallmark of healthy conditions in the female genital tract. Key nutrients for lactobacilli include sugars produced when...
Dominance of species in vaginal communities is a hallmark of healthy conditions in the female genital tract. Key nutrients for lactobacilli include sugars produced when glycogen is degraded by α-amylase in the vagina. While α-amylase activity has been demonstrated in vaginal fluids, it is unclear whether α-amylases are produced solely by the host, bacteria in the vagina, or both. We screened cervicovaginal mucus from 23 reproductive-age women, characterized the species composition of vaginal communities, measured vaginal pH, and determined levels of amylase activity, glycogen, and lactic acid. Based on differences in these measured variables, one sample from each of four individual donors was selected for metagenomic and proteomic analyses. Of eight putative bacterial amylases identified in the assembled bacterial metagenomes, we detected four in vaginal fluids. These amylases were produced by various bacteria in different vaginal communities. Moreover, no two communities were the same in terms of which bacteria were producing amylases. Although we detected bacterial amylases in vaginal fluids, there was no clear association between the bacterial species that was dominant in a community and the level of amylase activity. This association was likely masked by the presence of human α-amylase, which was also detected in vaginal fluids. Finally, the levels of amylase activity and glycogen were only weakly associated. Our findings show, for the first time, that multiple amylases from both bacterial and human origins can be present simultaneously in the vagina. This work also suggests that the link between glycogen, amylase, and in the vagina is complex. In this study, we show that multiple bacteria in the vaginal community produce amylases that hydrolyze glycogen into simpler sugars (i.e., maltose and maltotriose). These sugars serve as "common goods" that sustain bacterial populations in vaginal communities. Given the temporal changes that are observed in the human vaginal microbiome, we expect the kinds of bacterial amylases produced will also vary over time. These differences influence the pool of resources that are broadly shared and shape the species composition of the vaginal bacterial community.
Topics: Adult; Female; Glycogen; Humans; Hydrogen-Ion Concentration; Lactic Acid; Lactobacillus; Metagenome; Microbiota; Proteomics; Vagina; Vaginosis, Bacterial; alpha-Amylases
PubMed: 33298571
DOI: 10.1128/mSphere.00943-20 -
JBRA Assisted Reproduction Oct 2021To evaluate the newly formed epithelium that develops following a neovaginoplasty performed with Amniotic Membrane.
OBJECTIVE
To evaluate the newly formed epithelium that develops following a neovaginoplasty performed with Amniotic Membrane.
METHODS
A retrospective study conducted at the University Hospital of the Federal University, in Curitiba, Paraná, Brazil. A group of 33 patients with Vaginal Agenesis, most of them amenorrhoeic, either incapable of or having difficulty to perform sexual activity, were separated in Subgroup A (27 patients) with Mayer-Rokitansky-Kuster-Hauser Syndrome, and Subgroup B (six patients) with Androgenic Insensitivity Syndrome (Morris Syndrome). Intervention: Banister-McIndoe neovaginoplasty was performed using amniotic membrane graft in 33 patients of Subgroups A and B and evaluated 60-90 days later by vaginal epithelium biopsies. Main Outcome Measure(s): Transmission Electronic Microscopy (TEM) performed Biopsies of neovaginal epithelium in 10 patients. In 20 patients, we analyzed the levels of intensity and presence of Estrogenic Receptors.
RESULTS
Vaginal length was measured (vaginometry) before and after surgery. Before surgery, the vagina was absent in 5 patients (15.15%), vaginal length was 1 cm in 19 patients (57.58%) and in 9 patients (27.27%), it was between 2-3 cm. After surgery, all patients had a vaginal length greater or equal to 5 cm and, in 26 patients (78.8%), vaginal length was 7-8 cm. Seven to eight centimeters average neovagina length allowed patients to have a satisfactory sexual activity after all the surgical procedures to dilate, widen and distend the neomucosa lining. The ERs presented different levels of intensity in the three layers of the neovaginal mucosa. TEM analysis of the vaginal neoepithelium obtained from the amniotic membrane graft revealed all the characteristics of a trophic vaginal epithelium.
CONCLUSIONS
In a developing country like Brazil, neovaginoplasty with amniotic membrane graft is considered a great option, being an inexpensive, safe, and easy technique, not requiring any special materials. After a few days (60-90 days), or months, a new epithelium and vagina are obtained allowing patients to have proper sexual activity.
Topics: 46, XX Disorders of Sex Development; Epithelium; Female; Humans; Plastic Surgery Procedures; Retrospective Studies; Treatment Outcome; Vagina
PubMed: 34061487
DOI: 10.5935/1518-0557.20210016 -
Frontiers in Cellular and Infection... 2022The human microbiota influences physiology, disease, and metabolic reproduction. The origin of uterine bacteria is controversial. The main assumption is that the germs... (Review)
Review
The human microbiota influences physiology, disease, and metabolic reproduction. The origin of uterine bacteria is controversial. The main assumption is that the germs enter the uterine cavity from the vagina through the cervical canal, bloodstream, fallopian tubes, and gynecological surgical channels. Understanding the microbiota at various anatomical sites is critical to the female reproductive system and pregnancy. Today's study focuses on the role of uterine bacteria in pregnancy and embryo implantation. According to our findings, the uterine microbiome influences embryo implantation and pregnancy outcome. Pregnancy is a natural, evolutionarily selected approach to human reproduction. During pregnancy, the microbiota of the reproductive tract changes, facilitating the maintenance of pregnancy, and the human immune system undergoes a series of changes that recognize and adapt to the non-self. From the beginning of pregnancy, a non-self fetus must establish a placenta of embryonic origin to protect itself and promote growth; the VMB tends to be more stable and lactobacillus-dominated in late gestation than in early gestation. Any material that disrupts this connection, such as microbial changes, is associated with a higher risk of poor health and poor pregnancy outcomes in women (eclampsia). The presence of any material that disrupts this connection, such as microbial changes, is associated with a higher risk of poor health and poor pregnancy outcomes (preeclampsia, preterm birth, gestational diabetes, etc.). In this work, we review the last decade of relevant research to improve our understanding of the mechanisms by which the microbiota of the female reproductive tract influences female reproductive health. This work discusses the mechanisms associated with the reproductive tract microbiota and pregnancy immunity, as well as the impact of an abnormal microbiota on adverse pregnancy outcomes. Emphasis is placed on the characteristics and sources of the female vaginal, uterine, and placental microbiota and the importance of a well-stabilized local human microbiota and immune system for embryo implantation, placental development, fetal growth, and pregnancy outcome.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta; Premature Birth; Uterus; Cervix Uteri; Vagina; Bacteria
PubMed: 36683698
DOI: 10.3389/fcimb.2022.1025714 -
Viruses May 2022Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal-penile sex (heterosexual transmission). The local immune environment at the... (Review)
Review
Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal-penile sex (heterosexual transmission). The local immune environment at the site of HIV exposure is an important determinant of whether exposure during sex will lead to productive infection, and the vaginal and penile immune milieus are each critically shaped by the local microbiome. However, there are key differences in the microbial drivers of inflammation and immune quiescence at these tissue sites. In both, a high abundance of anaerobic taxa (e.g., ) is associated with an increased local density of HIV target cells and an increased risk of acquiring HIV through sex. However, the taxa that have been associated to date with increased risk in the vagina and penis are not identical. Just as importantly, the microbiota associated with comparatively less inflammation and HIV risk-i.e., the optimal microbiota-are very different at the two sites. In the vagina, spp. are immunoregulatory and may protect against HIV acquisition, whereas on the penis, "skin type" flora such as are associated with reduced inflammation. Compared to its vaginal counterpart, much less is known about the dynamics of the penile microbiome, the ability of clinical interventions to alter the penile microbiome, or the impact of natural/induced microbiome alterations on penile immunology and HIV risk.
Topics: Female; HIV Infections; HIV-1; Humans; Inflammation; Male; Penis; Vagina
PubMed: 35746636
DOI: 10.3390/v14061164 -
Frontiers in Immunology 2019A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms.... (Review)
Review
A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms. Infection with pathogenic microorganisms during pregnancy may lead to premature delivery, miscarriage, growth restriction, neonatal morbidity, and other adverse outcomes. Moreover, the host also has an intact immune system to avoid these adverse outcomes. It is important to note the presence of normal bacteria in the maternal reproductive tract and the principal role of the maternal-placental-fetal interaction in antimicrobial immunity. Previous studies mainly focused on maternal infection during pregnancy. However, this review summarizes the new views on the study of the maternal microbiome and expounds the innate immune defense mechanism of the maternal vagina and decidua as well as how cytotrophoblasts and syncytiotrophoblasts recognize and kill bacteria in the placenta. Fetal immune systems, thought to be weak, also exhibit an immune defense function that is indispensable for maintaining the safety of the fetus. The skin, lungs, and intestines of the fetus during pregnancy constitute the main immune barriers. These findings will provide a new understanding of the effects of normal microbial flora and how the host resists harmful microbes during pregnancy. We believe that it may also contribute to the reference on the clinical prevention and treatment of gestational infection to avoid adverse pregnancy outcomes.
Topics: Decidua; Female; Humans; Immunity, Innate; Maternal-Fetal Exchange; Microbiota; Pregnancy; Pregnancy Complications; Trophoblasts; Vagina
PubMed: 31921149
DOI: 10.3389/fimmu.2019.02886 -
Clinical Anatomy (New York, N.Y.) Oct 2021One of the transitional zones of the human body is situated in the cervix uteri. The developmental differentiation of epithelial and stromal characteristics in such a... (Review)
Review
INTRODUCTION
One of the transitional zones of the human body is situated in the cervix uteri. The developmental differentiation of epithelial and stromal characteristics in such a region is of high clinical interest. However, few studies have focused on the development of this region, and information in anatomical and clinical textbooks is limited. We therefore examined the development of the human vaginal fornix and the cervix uteri during prenatal development.
MATERIALS AND METHODS
We examined 29 female embryos and fetuses between 20 and 34 weeks and two newborns using histology and immunohistochemistry.
RESULTS
The characteristic shape of the portiocervicis and the vaginal fornix first became visible in mid-term fetuses because of the different muscular coats and of an uncategorized Müllerian-derived epithelium, which was rapidly replaced by a multilayered squamous epithelium. Only thereafter, in older fetuses, were there organogenetic differentiation of the epithelia and the underlying stroma of the cervical canal. UGS-derived p63/CK17-positive cells could be identified as precursor cells for the squamous epithelium, and Müllerian-derived CK7-positive cells for the columnar-type epithelium. Both cell types and different stromal zones were already present in a prenatal transformation zone. Initial functional differentiation could be observed in perinatal stages.
CONCLUSIONS
Our results on prenatal human development strongly support the view that two different cell lineages meet at the transitional zone of the cervix uteri and that these lineages depend on alternative signals from the underlying stromal compartment.
Topics: Cell Differentiation; Cervix Uteri; Epithelial Cells; Female; Fetus; Humans; Infant, Newborn; Vagina
PubMed: 33580897
DOI: 10.1002/ca.23729 -
Advances in Wound Care Apr 2021To design and validate a novel murine model of full-thickness (FT) vaginal wound healing that mirrors postinjury tissue repair and underscores the impact of estrogen...
To design and validate a novel murine model of full-thickness (FT) vaginal wound healing that mirrors postinjury tissue repair and underscores the impact of estrogen signaling-driven healing kinetics, inflammation, and neovascularization. Five-week-old female CD1 mice were subjected to two 1-mm FT wounds. To assess wound healing kinetics, vaginas were harvested at 6, 12, 18, 24, 48, and 72 h and 7 days postinjury. Wounds from all time points were analyzed by hematoxylin and eosin and trichrome to, respectively, assess the rate of wound closure and tissue deposition. Inflammatory leukocyte (CD45), neutrophil (Ly6G), and macrophage (F480 and CD206) infiltration was examined by immunohistochemistry (IHC) and the resulting anti-inflammatory M2 (CD206)/total (F480) macrophage ratio quantified. Neovascularization (CD31) and estrogen receptor-α (ERα) expression levels were similarly determined by IHC. We observed rapid healing with resolution of mucosal integrity by 48 h ( < 0.05), and overall neutrophils and polarized type 2 macrophages (M2) apexed at 12 h and reduced to near control levels by day 7 postinjury. Tissue repair was virtually indistinguishable from the surrounding vagina. CD31 vessels increased between 12 h and day 7 and ERα trended to decrease at 12 h postinjury and rebound at day 7 to uninjured levels. A proof-of-concept murine model to study vaginal wound healing kinetics and postinjury regenerative repair in the vagina was developed and verified. We surmise that murine vaginal mucosal repair is accelerated and potentially regulated by estrogen signaling through the ERα, thus providing a cellular and molecular foundation to understand vaginal healing responses to injury.
Topics: Animals; Estrogen Receptor alpha; Estrogens; Female; Inflammation; Kinetics; Macrophages; Mice; Models, Animal; Platelet Endothelial Cell Adhesion Molecule-1; Regeneration; Vagina; Wound Healing
PubMed: 32602816
DOI: 10.1089/wound.2020.1198 -
Clinical and Experimental Dermatology Dec 2022Oestrogen plays a vital role in maintaining a normal vulvovaginal epithelium, vaginal lubrication, as well as a healthy microbiome to ensure an acidic pH. The decrease... (Review)
Review
Oestrogen plays a vital role in maintaining a normal vulvovaginal epithelium, vaginal lubrication, as well as a healthy microbiome to ensure an acidic pH. The decrease in oestrogen levels in women going through menopause results in both physiological and physical changes of the genitourinary system, and more specifically the vulva. We conducted a literature review on the effects of low oestrogen levels on the physiology and function of the vulva and the vulvovaginal epithelium. 'Genitourinary syndrome of menopause' (GSM) is the term used to describe the signs and symptoms of a low oestrogen state. The symptoms and signs of GSM can overlap or coexist with other vulval dermatoses. Expert opinion is needed to diagnose and manage vulval dermatoses in menopause. This article will discuss the signs and symptoms of GSM, as well as the different management options available. Other vulval dermatoses that can be affected by hypo-oestrogenism are also reviewed.
Topics: Female; Humans; Vagina; Atrophy; Syndrome; Menopause; Estrogens; Skin Diseases
PubMed: 36103137
DOI: 10.1111/ced.15400 -
Journal of Reproductive Immunology Jun 2023There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients...
There have been few studies concerning an association between unexplained recurrent pregnancy loss (RPL) and the microbiome. A recent study including 67 patients demonstrated that an increase in Ureaplasma species in the endometrium raised the risk of miscarriage with an euploid karyotype. While endometrial sampling is invasive, cervicovaginal sampling is not. We compared vaginal and cervical microbiomes with a 16 S ribosomal RNA sequence between 88 patients with unexplained RPL and 17 healthy women with no history of miscarriage. We prospectively assessed risk factors for maternal colonization at a subsequent miscarriage without an aneuploid karyotype in patients. Cervicovaginal bacteria were dominated by Lactobacillus iners, Gardnerella vaginalis, Atopobium vaginae and Bifidobacterium breve in Japanese population. The proportions of Delftia and unknown bacteria in the cervix were significantly higher in patients with RPL than in controls. Streptococcus, Microbacterium, Delftia, Anaerobacillus and Chloroplast in the cervix were significantly higher in patients with a history of chorioamnionitis compared to the controls. The abundance of Cutibacterium and Anaerobacillus in the cervix was significantly higher in patients who had subsequently miscarried compared to those who gave birth. The miscarriage rate in patients with higher proportions of both Cutibacterium and Anaerobacillus (66.7%, 2/3) was significantly greater than that of patients who lacked these bacteria (9.2%, 6/65, adjusted odds ratio 16.90, 95% confidence interval 1.27-225.47, p = 0.032). The presence of certain bacteria could be a predictor of subsequent miscarriage without an aneuploid karyotype. The cervicovaginal microbiome might be useful for investigating a possible cause of RPL.
Topics: Pregnancy; Humans; Female; Vagina; Cervix Uteri; Abortion, Habitual; Aneuploidy; Microbiota
PubMed: 37060795
DOI: 10.1016/j.jri.2023.103944