scholarly journals The Female Reproductive Tract Microbiome—Implications for Gynecologic Cancers and Personalized Medicine

2021 ◽  
Vol 11 (6) ◽  
pp. 546
Author(s):  
Anthony E. Rizzo ◽  
Jennifer C. Gordon ◽  
Alicia R. Berard ◽  
Adam D. Burgener ◽  
Stefanie Avril

The microbial colonization of the lower female reproductive tract has been extensively studied over the past few decades. In contrast, the upper female reproductive tract including the uterine cavity and peritoneum where the ovaries and fallopian tubes reside were traditionally assumed to be sterile under non-pathologic conditions. However, recent studies applying next-generation sequencing of the bacterial 16S ribosomal RNA gene have provided convincing evidence for the existence of an upper female reproductive tract microbiome. While the vaginal microbiome and its importance for reproductive health outcomes has been extensively studied, the microbiome of the upper female reproductive tract and its relevance for gynecologic cancers has been less studied and will be the focus of this article. This targeted review summarizes the pertinent literature on the female reproductive tract microbiome in gynecologic malignancies and its anticipated role in future research and clinical applications in personalized medicine.

Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. KUBIAK

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.


2014 ◽  
Vol 128 (3) ◽  
pp. 153-180 ◽  
Author(s):  
Monica Logan ◽  
Shannon M. Hawkins

microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using in vitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract.


2020 ◽  
Vol 60 (3) ◽  
pp. 782-795 ◽  
Author(s):  
Teri J Orr ◽  
Virginia Hayssen

Synopsis Philosophical truths are hidden in Lewis Carroll’s nonsense poems, such as “The hunting of the snark.” When the poem is used as a scientific allegory, a snark stands for the pursuit of scientific truth, while a boojum is a spurious discovery. In the study of female biology, boojums have been the result of the use of cultural stereotypes to frame hypotheses and methodologies. Although female reproduction is key for the continuation of sexually reproducing species, not only have females been understudied in many regards, but also data have commonly been interpreted in the context of now-outdated social mores. Spurious discoveries, boojums, are the result. In this article, we highlight specific gaps in our knowledge of female reproductive biology and provide a jumping-off point for future research. We discuss the promise of emerging methodologies (e.g., micro-CT scanning, high-throughput sequencing, proteomics, big-data analysis, CRISPR-Cas9, and viral vector technology) that can yield insights into previously cryptic processes and features. For example, in mice, deoxyribonucleic acid sequencing via chromatin immunoprecipitation followed by sequencing is already unveiling how epigenetics lead to sex differences in brain development. Similarly, new explorations, including microbiome research, are rapidly debunking dogmas such as the notion of the “sterile womb.” Finally, we highlight how understanding female reproductive biology is well suited to the National Science Foundation’s big idea, “Predicting Rules of Life.” Studies of female reproductive biology will enable scholars to (1) traverse levels of biological organization from reproductive proteins at the molecular level, through anatomical details of the ovum and female reproductive tract, into physiological aspects of whole-organism performance, leading to behaviors associated with mating and maternal care, and eventually reaching population structure and ecology; (2) discover generalizable rules such as the co-evolution of maternal-offspring phenotypes in gestation and lactation; and (3) predict the impacts of changes to reproductive timing when the reliability of environmental cues becomes unpredictable. Studies in these key areas relative to female reproduction are sure to further our understanding across a range of diverse taxa.


PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9637 ◽  
Author(s):  
Chad J. Creighton ◽  
Ashley L. Benham ◽  
Huifeng Zhu ◽  
Mahjabeen F. Khan ◽  
Jeffrey G. Reid ◽  
...  

2021 ◽  
Vol 22 (11) ◽  
pp. 5644
Author(s):  
Irene Jiang ◽  
Paul J. Yong ◽  
Catherine Allaire ◽  
Mohamed A. Bedaiwy

Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished Lactobacillus dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine-impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has successfully predicted disease risk and stage. Future research should aim to characterize the “core” upper FRT microbiota and elucidate mechanisms behind the relationship between the microbiota and endometriosis.


1983 ◽  
Vol 4 (7) ◽  
pp. 212-230

Laparoscopy was performed on 140 female adolescents (aged 10 to 19 years) for chronic pelvic pain at Boston Children's Hospital Medical Center. Endometriosis (without other pelvic pathology) was encountered in 47% of these patients. Pelvic pain was both cyclic and acyclic and typically began 2.9 years after menarche. Other symptoms included irregular menses, gastrointestinal and bladder symptoms, and increased vaginal discharge. The diagnosis of endometriosis had not been made preoperatively in the majority of patients despite repeated pelvic examinations and thorough evaluation of gastrointestinal and genitourinary tracts. The most constant physical finding preoperatively was tenderness with or without cul-de-sac nodularity. Comment: Endometriosis is a disorder of the female reproductive tract characterized by the finding of endometrial tissue in locations outside the uterine cavity.


2020 ◽  
Vol 21 (21) ◽  
pp. 8264
Author(s):  
Rafał P. Piprek ◽  
Malgorzata Kloc ◽  
Paulina Mizia ◽  
Jacek Z. Kubiak

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood–testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.


Author(s):  
Angela J. Crean ◽  
Simone Immler

Variation in pre- and post-release gamete environments can influence evolutionary processes by altering fertilization outcomes and offspring traits. It is now widely accepted that offspring inherit epigenetic information from both their mothers and fathers. Genetic and epigenetic alterations to eggs and sperm-acquired post-release may also persist post-fertilization with consequences for offspring developmental success and later-life fitness. In externally fertilizing species, gametes are directly exposed to anthropogenically induced environmental impacts including pollution, ocean acidification and climate change. When fertilization occurs within the female reproductive tract, although gametes are at least partially protected from external environmental variation, the selective environment is likely to vary among females. In both scenarios, gamete traits and selection on gametes can be influenced by environmental conditions such as temperature and pollution as well as intrinsic factors such as male and female reproductive fluids, which may be altered by changes in male and female health and physiology. Here, we highlight some of the pathways through which changes in gamete environments can affect fertilization dynamics, gamete interactions and ultimately offspring fitness. We hope that by drawing attention to this important yet often overlooked source of variation, we will inspire future research into the evolutionary implications of anthropogenic interference of gamete environments including the use of assisted reproductive technologies. This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’


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