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Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus. It affects many women during their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, which limits early diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared them to matched eutopic endometrium, unaffected endometrium and organoids derived from these tissues, generating data on over 122,000 cells across 14 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell specific to the peritoneal lesions, with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesion microenvironments and an unreported progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment that represents a comprehensive cell atlas of the disease in individuals undergoing hormonal treatment, providing essential information for future therapeutics and diagnostics. Using single-cell analysis, Tan et al. map the cellular and spatial hierarchy and heterogeneity of eutopic endometrium and characterize ectopic peritoneal and ovarian endometriosis lesions from individuals receiving hormone treatment.

BackgroundEndometriosis is a risk factor for ovarian cancer. Endometriosis-associated ovarian cancer (EAOC), most commonly clear cell carcinoma, is believed to develop from ovarian endometrial cysts. In this study, we reviewed published cases of EAOC considered to have developed from endometrial cysts, and focused on the observation period.MethodsWe searched for articles published since January 2000 that reported cases of ovarian cancer thought to have originated from endometrial cysts using PubMed, Web of Science, and Ichushi-Web. The period from the start of follow-up of the endometrial cyst to the diagnosis of ovarian cancer was calculated.ResultsSeventy-nine cases were identified from 32 articles. The median period from the diagnosis of endometrial cysts to the diagnosis of ovarian cancer was only 36 months. Approximately 75% of cases developed into cancer within 60 months and most cases developed within 120 months.ConclusionOur results suggest that clinically detectable cysts subsequently diagnosed as ovarian cancer might already have contained cancer cells. Therefore, the mechanism of EAOC development needs to be re-examined and appropriate management guidelines need to be developed.

A significant factor contributing to reproductive failure in dairy cattle that raised the possibility of culling was ovarian cysts. Its etiology and pathogenesis remained a puzzle, but investigation of the associated tissue modulation, particularly those of the ovaries, oviduct, and uterus, might shed some light on its development. Therefore, the current study aimed to assess changes induced by follicular and luteal cyst formation in the ovary, oviduct, and uterus. In addition, the aims also involved the effect of these cyst formations on the interstitial glands and mast cell distribution in the ovaries of dairy cows. Genital organs of healthy, non-pregnant buffalo-cows ( n  = 45) were collected from the abattoir. According to the ovarian status, buffalo-cows were divided into three equal groups (15 for each): one normal healthy group was the control group (Ctrl group) and two diseased groups. The first diseased group was the group of buffalo-cows with follicular cysts (FC group), while the second one was the group with luteal cysts (LC group). Blood and tissue samples were collected to determine progesterone levels and do histological investigations of the reproductive organs. Hematoxylin and eosin, Alcian blue-PAS, and Alcian blue-safranin-O stains were used for investigating ovarian tissues, interstitial glands (IGs), and mast cells (MCs), respectively. Results showed that significantly reduced thickness of the ovarian cortex and medulla, loss of ovarian folliculi, hemorrhage, and dilated blood vessels were observed in the FC and LC groups compared to the Ctrl group. In addition, the cystic ovaries significantly reduced interstitial gland count that was characterized by histopathological alterations that included atrophied and apoptotic cells and fragmentation, fading, and pyknotic nuclei. Likewise, in cystic ovaries, mast cell counts were found significantly reduced compared to the Ctrl group. The ovarian cysts significantly reduced the length and diameter of oviductal mucosal villi that were characterized by severe histopathological fluctuation in the ciliated cells and protruding and non-protruding secretory cells. For the uterus, the average thickness of the myometrium and endometrium in the ovarian cyst groups was significantly reduced compared to the Ctrl group. Furthermore, histopathological changes in the uterine glands, including severe apoptotic alterations, fading, pyknotic, and fragmented nuclei, were observed. In conclusion, the current study indicated that follicular and luteal cyst formations in the ovary induced various changes in the reproductive organs, interstitial glands, and mast cell distribution in the ovarian stroma, providing insights into the potential pathogenesis of cyst formation.

Background Ovarian cystic lesions are typically slow-growing neoplasms, but giant ovarian tumors with dual histological types are rare, particularly in pediatric populations. They pose significant diagnostic and therapeutic challenges due to the potential for rapid enlargement and surgical complexity. Case presentation A 12-year-old female presented with progressive abdominal pain, early satiety, and a two-month history of abdominal distension. Imaging revealed a 30 × 22 × 12 cm intraperitoneal cystic mass with negative tumor markers. She underwent mini-laparotomy and tumor enucleation, during which 4400 cc of serous fluid was aspirated. Histopathology revealed a serous cystadenoma alongside a hemorrhagic corpus luteal cyst. Fertility was successfully preserved. Discussion Despite their rarity, large benign ovarian cysts with differing histology should be considered in young patients presenting with abdominal symptoms suggestive of malignancy. Early imaging, tumor marker evaluation, and fertility-preserving surgical strategies are crucial for optimal outcomes. Conclusion Benign giant ovarian cysts with concurrent histological types may mimic malignancy. Thorough preoperative evaluation and conservative surgical management are essential to balance oncological safety with fertility preservation in pediatric patients.

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner's subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images.

We describe a case of bilateral ovarian tumor-like lesions detected during pregnancy. It is important to highlight that these masses were not detected for the first time during pregnancy; the patient had already been aware of them 2 years prior, during pregnancy preparation, when an ultrasound examination revealed bilateral space-occupying ovarian lesions. These lesions did not exhibit any increase in size during regular follow-ups until pregnancy. At 17 weeks of gestation, fetal ultrasound showed significant enlargement of the bilateral ovarian lesions. The patient underwent pelvic magnetic resonance imaging, which revealed cystic masses in both the ovaries with septations and multiple nodular and flocculent projections on the walls and septations, exhibiting features resembling malignant tumors. The cystic fluid within each cyst predominantly showed slightly short T1 and long T2 signal characteristics. The final diagnosis of lesions occupying the ovarian space was endometriotic cysts with a decidual reaction associated with pregnancy, which was confirmed on postoperative pathological examination. Subsequently, at 19 weeks of gestation, the patient underwent a “laparoscopic excision of the left ovarian lesion and right ovarian lesion stripping.” The patient recovered well postoperatively and successfully delivered a baby at 39 weeks of gestation. Endometriosis with decidual reaction during pregnancy is rare and ectopic decidual tissue can easily be confused with neoplastic lesions using imaging results. In addition, clinicians must remain vigilant about the special conditions that ectopic decidual tissue may cause, such as cyst rupture, massive hemorrhage, dystocia, and even fetal death.

The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

Purpose To investigate the clinical characteristics and prognosis of surgically treated ovarian endometrioma (OMA) in pregnant women. Methods This retrospective cohort study analyzed 30 patients with pathologically confirmed ovarian endometrioma during pregnancy and delivery. Clinical characteristics and follow-up data were summarized. Results Among the 30 patients, 21 underwent laparoscopic surgery during pregnancy. A total of 24 OMAs were identified in 21 patients and exhibited various changes during pregnancy: 13 did not show significant changes, 10 increased in size and 1 decreased in size. The indications for surgery included suspicion of malignancy (16/21), large and progressive growth (3/21), and ovarian cyst torsion (2/21). The postoperative pathology results showed that decidualization occurred in 7 cases, while only 1 case was diagnosed with malignancy, and there appears to be a lack of specific clinical characteristics to distinguish between malignant cysts and de ci du a l I zed cysts. Of the 21 patients, 19 underwent successful follow-up. Among them, 2 cases were preterm births, 1 experienced recurrence, and 2 developed adenomyosis during long-term follow-up. Besides, 9 patients underwent cystectomy during the cesarean section. All the ultrasound findings showed regular and smooth-walled unilocular cysts, with diameters smaller than 6 cm and no apparent growth during pregnancy. Postoperative pathology revealed decidualization in 3 cases, and 1 case experienced recurrence during follow-up. Conclusions OMA presents various changes during pregnancy and caution should also be taken for recurrence after delivery. Surgical intervention is prompted mainly by suspected malignancies which is difficult to distinguish with decidualization, and laparoscopic surgery is relatively safe during mid-pregnancy.

Background This study aimed to compare the expression patterns of hypoxia-inducible factor-1α in ovarian cyst capsules and endometrial tissue samples from patients with and without endometriosis to evaluate its potential as a biomarker of hypoxia in endometriosis. Methods This retrospective observational case–control study included 87 women of childbearing age (20–45 years) who underwent ovarian cystectomy at Balıkesir University Hospital between 2015 and 2020. Of these, 40 patients with confirmed endometriosis constituted the study group, while 47 patients with benign ovarian cysts comprised the control group. Immunohistochemical staining was used to assess the expression of hypoxia-inducible factor-1-alpha in ovarian cyst capsules and endometrial tissue samples. The relationship between the expression of hypoxia-inducible factor-1-alpha and clinical parameters, including age, body mass index, and endometriosis stage, was also evaluated. Results The expression of hypoxia-inducible factor-1-alpha was significantly higher in ovarian cyst capsules and endometrial tissues of patients with endometriosis than in those of controls (p < 0.05). No correlation was found between hypoxia-inducible factor-1-alpha expression and age, body mass index, or disease stage. Conclusions In this study, the expression of hypoxia-inducible factor-1-alpha in the ovarian and endometrial tissues was significantly elevated in patients with endometriosis compared with that in controls, independent of clinical parameters. These results support hypoxia-inducible factor-1-alpha as a stable biomarker of hypoxia in endometriosis and provide a basis for future research on hypoxia-targeted therapies for endometriosis management.

Epidemiologic and histopathologic findings and the laying hen model support the long-standing incessant ovulation hypothesis and cortical inclusion cyst involvement in sporadic ovarian cancer development. MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. Herewith, we show that ovarian surface epithelial (OSE) cells with ectopic miR-200 expression formed stabilized cysts in three-dimensional (3D) organotypic culture with E-cadherin fragment expression and steroid hormone pathway activation, whereas ovarian cancer 3D cultures with miR-200 knockdown showed elevated TGF-β expression, mitotic spindle disorientation, increased lumenization, disruption of ROCK-mediated myosin II phosphorylation, and SRC signaling, which led to histotype-dependent loss of collective movement in tumor spread. Gene expression profiling revealed that epithelial–mesenchymal transition and hypoxia were the top enriched gene sets regulated by miR-200 in both OSE and ovarian cancer cells. The molecular changes uncovered by the in vitro studies were verified in both human and laying hen ovarian cysts and tumor specimens. As miR-200 is also essential for ovulation, our results of estrogen pathway activation in miR-200-expressing OSE cells add another intriguing link between incessant ovulation and ovarian carcinogenesis.