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Developmental Cell Apr 2022Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied...
Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied single-cell RNA-seq to profile 59,738 FT cells from four healthy, pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal, and immune compartments. Re-clustering of epithelial cells identified four ciliated and six non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells and the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed 17,798 cells from two hydrosalpinx samples and observed shifts in epithelial and stromal populations and cell-type-specific changes in extracellular matrix and TGF-β signaling; this underscores fibrosis pathophysiology. This resource is expected to facilitate future studies aimed at expanding understanding of fallopian tube homeostasis in normal development and disease.
Topics: Epithelial Cells; Fallopian Tubes; Female; Humans; Ovarian Neoplasms; Single-Cell Analysis
PubMed: 35320732
DOI: 10.1016/j.devcel.2022.02.017 -
Cell Reports Apr 2021The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the...
The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3 intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.
Topics: Adult; Cell Differentiation; Cell Line, Tumor; Core Binding Factor Alpha 3 Subunit; Endometriosis; Epithelial Cells; Epithelial-Mesenchymal Transition; Fallopian Tubes; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Leiomyoma; Middle Aged; PAX8 Transcription Factor; SOXF Transcription Factors; Signal Transduction; Single-Cell Analysis; Transcriptome
PubMed: 33852846
DOI: 10.1016/j.celrep.2021.108978 -
Fertility and Sterility Nov 2020
Topics: Endometriosis; Fallopian Tube Diseases; Fallopian Tubes; Female; Humans; Infertility, Female; Laparoscopy
PubMed: 32854933
DOI: 10.1016/j.fertnstert.2020.07.045 -
Ugeskrift For Laeger Jul 2023In this case report, a woman with no risk factors was admitted with bilateral tubal ectopic pregnancy. Bilateral ectopic pregnancy is a rare clinical condition with...
In this case report, a woman with no risk factors was admitted with bilateral tubal ectopic pregnancy. Bilateral ectopic pregnancy is a rare clinical condition with clinical findings which in their symptoms do not differ from those of unilateral ectopic pregnancy. The condition can therefore easily be missed. The risk of rupture and haemorrhagic shock might be increased because of the increased danger of both tubes presenting with complications. Thus, it is important to examine both adnexa by transvaginal ultrasound. Even if unilateral ectopic pregnancy is considered before operation, the inspection of the abdomen, especially of the other fallopian tube, must always be done during surgery.
Topics: Pregnancy; Female; Humans; Pregnancy, Tubal; Pregnancy, Ectopic; Fallopian Tubes; Ultrasonography; Rupture
PubMed: 37539800
DOI: No ID Found -
International Journal of Molecular... Nov 2020In mammals, the oviduct (or the Fallopian tube in humans) can be divided into the infundibulum (responsible for oocyte pick-up), ampulla (site of fertilization), isthmus... (Review)
Review
In mammals, the oviduct (or the Fallopian tube in humans) can be divided into the infundibulum (responsible for oocyte pick-up), ampulla (site of fertilization), isthmus (where preimplantation embryos develop), and uterotubal junction (where embryos transit to the uterus). The oviductal fluid, as well as extracellular vesicles produced from the oviduct epithelial cells, referred to as oEVs, have been shown to improve the fertilization process, prevent polyspermy, and aid in embryo development. oEVs contain molecular cargos (such as miRNAs, mRNAs, proteins, and lipids) that can be delivered and fuse to recipient cells. oEVs produced from the ampulla appear to be functionally distinct from those produced from the isthmus. In multiple species including mice, cats, dogs, pigs, and cows, oEVs can be incorporated into the oocytes, sperm, and embryos. In this review, we show the positive impact of oEVs on gamete function as well as blastocyst development and how they may improve embryo quality in in vitro conditions in an assisted reproductive technology setting for rodents, domestic animals, farm animals, and humans.
Topics: Animals; Blastocyst; Cats; Cattle; Cells, Cultured; Dogs; Embryonic Development; Extracellular Vesicles; Fallopian Tubes; Female; Germ Cells; Humans; Mice; Oviducts; Pregnancy; Reproductive Techniques, Assisted; Swine
PubMed: 33167378
DOI: 10.3390/ijms21218280 -
Folia Medica Cracoviensia 2016Infertility is actually widespread pathological condition, which affected one in every four couples in developing countries. Approximately one third of all cases are... (Review)
Review
Infertility is actually widespread pathological condition, which affected one in every four couples in developing countries. Approximately one third of all cases are connected with tubal factor infertility, o en accompanies by endometriosis, acute salpingitis, urogenital infections etc. The newly identified telocytes (TCs) have multiple potential bio-functions and might participate in the fertility problems. They influence on structural and functional integrity of oviduct tissue. Despite recent discovery, TCs involvement in the majority of physiological and pathological processes is still unclear and require significant increasing of deep observations and data analysis. Focusing on female reproductive system help better understands the main reasons of infertility, while evaluation of TCs impact on Fallopian tube and uterus contractility might be a key point of its correction. The article summarizes the main features of telocytes in Fallopian tubes, emphasizing their involvement in pathophysiological processes and tubal factor infertility.
Topics: Fallopian Tubes; Female; Humans; Infertility, Female; Risk Factors; Telocytes
PubMed: 28013318
DOI: No ID Found -
Journal of Histotechnology Mar 2022Falloposcopy is the endoscopic examination of the fallopian tubes, which are challenging to access due to their deep body location, small opening from the uterus, and...
Falloposcopy is the endoscopic examination of the fallopian tubes, which are challenging to access due to their deep body location, small opening from the uterus, and lumen filled with plicae. We and others have developed endoscopes that are inserted through the uterus guided by a hysteroscope into the tubal ostium. To better understand how to utilize these endoscopes either as standalone devices or in concert with everting delivery balloons, a preliminary study of anatomy and mechanical behavior was performed on porcine and human fallopian tubes. Segments of fallopian tubes from the isthmus, ampulla and infundibulum were inflated with saline either to bursting or held at sub-burst pressures with saline or a saline-filled balloon. Formalin fixed, paraffin embedded tissue sections stained with Masson's trichrome were examined for damage to the mucosa and muscularis. Porcine fallopian tubes tolerated saline pressurization at 15 psi for 1 minute without morphological damage. Balloon inflation to 15 psi caused no apparent damage to the muscle layer or rupture of the fallopian tube, but balloon movement within the tube can denude the mucosal epithelial layer. Human fallopian tubes averaged higher burst pressure values than porcine tubes. Under pressurization, the external tube diameter expanded by minimal to moderate amounts. Human and porcine tissues were similar in histological appearance. These studies suggest that moderate pressurization is acceptable but will not appreciably expand the fallopian tube diameter. The results also indicate that pigs are a reasonable model to study damage from falloscopy as seen in human tissue.
Topics: Animals; Endoscopes; Fallopian Tubes; Female; Humans; Hysteroscopes; Laparoscopy; Swine; Uterus
PubMed: 34496720
DOI: 10.1080/01478885.2021.1972250 -
Scientific Reports Sep 2022The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging...
The heterogeneity in the pathological and clinical manifestations of ovarian cancer is a major hurdle impeding early and accurate diagnosis. A host of imaging modalities, including Doppler ultrasound, MRI, and CT, have been investigated to improve the assessment of ovarian lesions. We hypothesized that pathologic conditions might affect the ovarian vasculature and that these changes might be detectable by optical-resolution photoacoustic microscopy (OR-PAM). In our previous work, we developed a benchtop OR-PAM and demonstrated it on a limited set of ovarian and fallopian tube specimens. In this study, we collected data from over 50 patients, supporting a more robust statistical analysis. We then developed an efficient custom analysis pipeline for characterizing the vascular features of the samples, including the mean vessel diameter, vascular density, global vascular directionality, local vascular definition, and local vascular tortuosity/branchedness. Phantom studies using carbon fibers showed that our algorithm was accurate within an acceptable error range. Between normal ovaries and normal fallopian tubes, we observed significant differences in five of six extracted vascular features. Further, we showed that distinct subsets of vascular features could distinguish normal ovaries from cystic, fibrous, and malignant ovarian lesions. In addition, a statistically significant difference was found in the mean vascular tortuosity/branchedness values of normal and abnormal tubes. The findings support the proposition that OR-PAM can help distinguish the severity of tubal and ovarian pathologies.
Topics: Carbon Fiber; Fallopian Tubes; Female; Humans; Microscopy; Ovarian Cysts; Ovarian Neoplasms
PubMed: 36151126
DOI: 10.1038/s41598-022-19778-1 -
Nature Communications Oct 2017High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be...
High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients. The majority of tumor-specific alterations in ovarian cancers were present in STICs, including those affecting TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and STICs are precursors of ovarian carcinoma and identify a window of 7 years between development of a STIC and initiation of ovarian carcinoma, with metastases following rapidly thereafter. Our results provide insights into the etiology of ovarian cancer and have implications for prevention, early detection and therapeutic intervention of this disease.
Topics: Alleles; Cystadenocarcinoma, Serous; DNA Copy Number Variations; Fallopian Tube Neoplasms; Fallopian Tubes; Female; Humans; Immunohistochemistry; Laser Capture Microdissection; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms
PubMed: 29061967
DOI: 10.1038/s41467-017-00962-1 -
Communications Biology Dec 2022Most ovarian high-grade serous carcinomas (HGSC) arise from Serous Tubal Intraepithelial Carcinoma (STIC) lesions in the distal end of the fallopian tube (FT). Formation...
Most ovarian high-grade serous carcinomas (HGSC) arise from Serous Tubal Intraepithelial Carcinoma (STIC) lesions in the distal end of the fallopian tube (FT). Formation of STIC lesions from FT secretory cells leads to seeding of the ovarian surface, with rapid tumor dissemination to other abdominal structures thereafter. It remains unclear how nascent malignant cells leave the FT to colonize the ovary. This report provides evidence that the L1 cell adhesion molecule (L1CAM) contributes to the ability of transformed FT secretory cells (FTSEC) to detach from the tube, survive under anchorage-independent conditions, and seed the ovarian surface. L1CAM was highly expressed on the apical cells of STIC lesions and contributed to ovarian colonization by upregulating integrins and fibronectin in malignant cells and activating the AKT and ERK pathways. These changes increased cell survival under ultra-low attachment conditions that mimic transit from the FT to the ovary. To study dissemination to the ovary, we developed a tumor-ovary co-culture model. We showed that L1CAM expression was important for FT cells to invade the ovary as a cohesive group. Our results indicate that in the early stages of HGSC development, transformed FTSECs disseminate from the FT to the ovary in a L1CAM-dependent manner.
Topics: Female; Humans; Fallopian Tubes; Neural Cell Adhesion Molecule L1; Ovarian Neoplasms; Fallopian Tube Neoplasms; Cystadenocarcinoma, Serous
PubMed: 36509990
DOI: 10.1038/s42003-022-04314-8