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CytoJournal 2022Peritoneal washings used for cytologic evaluation are collected at the outset of surgical exploration of women with gynecologic cancers to assist in determining extent... (Review)
Review
Peritoneal washings used for cytologic evaluation are collected at the outset of surgical exploration of women with gynecologic cancers to assist in determining extent of disease and follow-up therapy. While there are similarities to ascites, these samples have differences that must be recognized in order to avoid false positive interpretations. Non-neoplastic mesothelial alterations including heterogeneous reactive changes, endosalpingiosis , endometriosis and tumor rupture are typically not seen in ascites samples but can be seen in peritoneal washings from women with malignancies that have not extended to the peritoneal cavity. Awareness of these potential pitfalls and knowledge of the associated tumor type will facilitate accurate interpretation. When these caveats are recognized, peritoneal washing cytology results are a useful adjunct in helping to determine patient follow-up in women with gynecologic malignancies.
PubMed: 35510121
DOI: 10.25259/CMAS_02_07_2021 -
Journal of Personalized Medicine Jan 2024Despite the increased frequency of endometriosis, it remains one of the most enigmatic disorders regarding its effects on pregnancy. Endometriosis adversely affects both... (Review)
Review
Despite the increased frequency of endometriosis, it remains one of the most enigmatic disorders regarding its effects on pregnancy. Endometriosis adversely affects both natural and assisted conception. Impaired folliculogenesis, which causes follicular dysfunction and low egg quality, as well as luteal phase problems, reduced fertilization, and abnormal embryogenesis, are some of the mechanisms advocated to explain reproductive dysfunction. There is a rising need for a comprehensive study of the potential negative consequences of this condition on pregnancy outcomes, including the postpartum period, as more women with a medical history of endometriosis become pregnant. Obstetrical complications (small for gestational age [SGA], cesarean section [CS], miscarriage, hemorrhage, low placental adhesion, and preterm delivery) are statistically elevated in women with endometriosis. Furthermore, ruptured ovarian endometrioma, appendicitis, intestinal perforation, and hemoperitoneum have been described in pregnancy. Obstetricians are largely unfamiliar with these complications, as they have not been thoroughly investigated. The development and pathogenesis of endometriosis is an important field of study and has not yet been fully elucidated. Finding these mechanisms is crucial for the development of new and more effective strategies to treat this condition. Endometriosis can have an impact on obstetric and neonatal outcomes of pregnancy, in addition to its potential effects on conception. To date, no additional monitoring is recommended for pregnancies with a history of endometriosis. However, more studies are urgently needed to assess the need for the tailored pregnancy monitoring of women with endometriosis.
PubMed: 38276248
DOI: 10.3390/jpm14010126 -
Frontiers in Physiology 2022In clinical practice, ovarian pregnancy is extremely rare and is always found to be ruptured. A definitive diagnosis for ruptured ovarian pregnancy is difficult to... (Review)
Review
In clinical practice, ovarian pregnancy is extremely rare and is always found to be ruptured. A definitive diagnosis for ruptured ovarian pregnancy is difficult to obtain. We present two cases of unruptured ovarian pregnancies detected during laparoscopy and review existing literature to better understand the clinical characteristics of ectopic pregnancies in this rare site. Intrauterine devices, assisted reproductive technology, and intrauterine operations are all high-risk factors in ovarian pregnancy. Moreover, menopause, abdominal pain, and vaginal bleeding are clinical manifestations. Ovarian pregnancy can be diagnosed using serum hCG, transvaginal ultrasound, and magnetic resonance imaging. Laparoscopy is the treatment of choice for ovarian pregnancy. It is recommended that the intact gestational sac be excised and the ovarian function be protected to the greatest extent possible during the operation. More definitive diagnosis of ovarian pregnancy must be reported in order to gain a better understanding of ovarian pregnancy.
PubMed: 36388130
DOI: 10.3389/fphys.2022.1036365 -
Scientific Reports Jul 2022Bexarotene selectively activates retinoid X receptor, which is a commonly used anticancer agent for cutaneous T-cell lymphoma. In this study, we aimed to investigate the...
Bexarotene selectively activates retinoid X receptor, which is a commonly used anticancer agent for cutaneous T-cell lymphoma. In this study, we aimed to investigate the anticancer effect of bexarotene and its underlying mechanism in ovarian cancer in vitro. The ES2 and NIH:OVACAR3 ovarian cancer cell lines were treated with 0, 5, 10, or 20 µM of bexarotene. After 24 h, cell number measurement and lactate dehydrogenase (LDH) cytotoxicity assay were performed. The effect of bexarotene on CDKN1A expression, cell cycle-related protein, cell cycle, pyroptosis, and apoptosis was evaluated. Bexarotene reduced cell proliferation in all concentrations in both the cells. At concentrations of > 10 µM, extracellular LDH activity increased with cell rupture. Treatment using 10 µM of bexarotene increased CDKN1A mRNA levels, decreased cell cycle-related protein expression, and increased the sub-G1 cell population in both cells. In ES2 cells, caspase-4 and GSDME were activated, whereas caspase-3 was not, indicating that bexarotene-induced cell death might be pyroptosis. A clinical setting concentration of bexarotene induced cell death through caspase-4-mediated pyroptosis in ovarian cancer cell lines. Thus, bexarotene may serve as a novel therapeutic agent for ovarian cancer.
Topics: Bexarotene; Carcinoma, Ovarian Epithelial; Cell Cycle Proteins; Cell Death; Female; Humans; Ovarian Neoplasms; Pyroptosis; Skin Neoplasms
PubMed: 35778597
DOI: 10.1038/s41598-022-15348-7 -
Turkish Journal of Obstetrics and... Dec 2020Hemorrhagic corpus luteum (HCL) is an ovarian cyst formed after ovulation and caused by spontaneous bleeding into a corpus luteum (CL) cyst. When HCL rupture happens, a... (Review)
Review
Hemorrhagic corpus luteum (HCL) is an ovarian cyst formed after ovulation and caused by spontaneous bleeding into a corpus luteum (CL) cyst. When HCL rupture happens, a hemoperitoneum results. Clinical symptoms are mainly due to peritoneal irritation by the blood effusion. The differential diagnosis is extensive and standard management is not defined. The authors elaborated a comparison of the differential diagnosis and therapeutic modalities from the laparoscopic approach to nonsurgical, medical options because hemorrhage from HCL is often self-limiting. The authors reviewed all data implicated with the development of HCL, trying to give homogeneity to literature data. The authors analyzed extensive literature data and subdivided the medical approach into many topics. The wait-and-see attitude avoids unnecessary laparoscopic surgery using supportive therapies (antifibrinolytic, analgesics, liquid infusion, transfusions and antibiotic prophylaxis). Surgical therapy: operative management should be laparoscopic, with surgical options such as luteumectomy, ovarian wedge-shaped excision or oophorectomy. Prevention: the possibility to preserve fertility is essential, mainly in patients with bleeding disorders or undergoing anticoagulant therapy; therefore, they need estro-progestinics or GnRH analogues to prevent ovulation and avoid further episodes of HCL. This review will aid physicians in making an early diagnosis of HCL, to avoid unnecessary surgery, and use the most effective treatment.
PubMed: 33343977
DOI: 10.4274/tjod.galenos.2020.40359 -
Biological Reviews of the Cambridge... Oct 2023Ovulation is a cyclical biological rupture event fundamental to fertilisation and endocrine function. During this process, the somatic support cells that surround the... (Review)
Review
Ovulation is a cyclical biological rupture event fundamental to fertilisation and endocrine function. During this process, the somatic support cells that surround the germ cell undergo a remodelling process that culminates in breakdown of the follicle wall and release of a mature egg. Ovulation is driven by known proteolytic and inflammatory pathways as well as structural alterations to the follicle vasculature and the fluid-filled antral cavity. Ovulation is one of several types of systematic remodelling that occur in the human body that can be described as rupture. Although ovulation is a physiological form of rupture, other types of rupture occur in the human body which can be pathological, physiological, or both. In this review, we use intracranial aneurysms and chorioamniotic membrane rupture as examples of rupture events that are pathological or both pathological and physiological, respectively, and compare these to the rupture process central to ovulation. Specifically, we compared existing transcriptomic profiles, immune cell functions, vascular modifications, and biomechanical forces to identify common processes that are conserved between rupture events. In our transcriptomic analysis, we found 12 differentially expressed genes in common among two different ovulation data sets and one intracranial aneurysm data set. We also found three genes that were differentially expressed in common for both ovulation data sets and one chorioamniotic membrane rupture data set. Combining analysis of all three data sets identified two genes (Angptl4 and Pfkfb4) that were upregulated across rupture systems. Some of the identified genes, such as Rgs2, Adam8, and Lox, have been characterised in multiple rupture contexts, including ovulation. Others, such as Glul, Baz1a, and Ddx3x, have not yet been characterised in the context of ovulation and warrant further investigation as potential novel regulators. We also identified overlapping functions of mast cells, macrophages, and T cells in the process of rupture. Each of these rupture systems share local vasoconstriction around the rupture site, smooth muscle contractions away from the site of rupture, and fluid shear forces that initially increase and then decrease to predispose one specific region to rupture. Experimental techniques developed to study these structural and biomechanical changes that underlie rupture, such as patient-derived microfluidic models and spatiotemporal transcriptomic analyses, have not yet been comprehensively translated to the study of ovulation. Review of the existing knowledge, transcriptomic data, and experimental techniques from studies of rupture in other biological systems yields a better understanding of the physiology of ovulation and identifies avenues for novel studies of ovulation with techniques and targets from the study of vascular biology and parturition.
Topics: Animals; Female; Humans; Ovulation; Ovarian Follicle; Mammals; Biology
PubMed: 37157877
DOI: 10.1111/brv.12970 -
Cancer Medicine Dec 2023As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based...
AIM
As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment.
METHODS
A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed.
RESULTS
Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1-positive samples were more common in the chemoresistant group than in the platinum-sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis.
CONCLUSION
This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.
Topics: Female; Humans; Tryptophan; Tryptophan Oxygenase; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; L-Amino Acid Oxidase
PubMed: 38062922
DOI: 10.1002/cam4.6778 -
Proceedings of the National Academy of... Jan 2024Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal...
Ovulation is essential for reproductive success, yet the underlying cellular and molecular mechanisms are far from clear. Here, we applied high-resolution spatiotemporal transcriptomics to map out cell type- and ovulation stage-specific molecular programs as function of time during follicle maturation and ovulation in mice. Our analysis revealed dynamic molecular transitions within granulosa cell types that occur in tight coordination with mesenchymal cell proliferation. We identified molecular markers for the emerging cumulus cell fate during the preantral-to-antral transition. We describe transcriptional programs that respond rapidly to ovulation stimulation and those associated with follicle rupture, highlighting the prominent roles of apoptotic and metabolic pathways during the final stages of follicle maturation. We further report stage-specific oocyte-cumulus cell interactions and diverging molecular differentiation in follicles approaching ovulation. Collectively, this study provides insights into the cellular and molecular processes that regulate mouse ovarian follicle maturation and ovulation with important implications for advancing therapeutic strategies in reproductive medicine.
Topics: Female; Animals; Mice; Ovary; Ovulation; Ovarian Follicle; Reproduction; Granulosa Cells; Ascomycota
PubMed: 38252830
DOI: 10.1073/pnas.2317418121 -
Frontiers in Endocrinology 2023Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and... (Review)
Review
Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of congenital adrenal hyperplasia that can manifest with skeletal malformations, ambiguous genitalia, and menstrual disorders caused by cytochrome P450 oxidoreductase (POR) mutations affecting electron transfer to all microsomal cytochrome P450 and some non-P450 enzymes involved in cholesterol, sterol, and drug metabolism. With the advancement of molecular biology and medical genetics, increasing numbers of PORD cases were reported, and the clinical spectrum of PORD was extended with studies on underlying mechanisms of phenotype-genotype correlations and optimum treatment. However, diagnostic challenges and management dilemma still exists because of unawareness of the condition, the overlapping manifestations with other disorders, and no clear guidelines for treatment. Delayed diagnosis and management may result in improper sex assignment, loss of reproductive capacity because of surgical removal of ruptured ovarian macro-cysts, and life-threatening conditions such as airway obstruction and adrenal crisis. The clinical outcomes and prognosis, which are influenced by specific POR mutations, the presence of additional genetic or environmental factors, and management, include early death due to developmental malformations or adrenal crisis, bilateral oophorectomies after spontaneous rupture of ovarian macro-cysts, genital ambiguity, abnormal pubertal development, and nearly normal phenotype with successful pregnancy outcomes by assisted reproduction. Thus, timely diagnosis including prenatal diagnosis with invasive and non-invasive techniques and appropriate management is essential to improve patients' outcomes. However, even in cases with conclusive diagnosis, comprehensive assessment is needed to avoid severe complications, such as chromosomal test to help sex assignment and evaluation of adrenal function to detect partial adrenal insufficiency. In recent years, it has been noted that proper hormone replacement therapy can lead to decrease or resolve of ovarian macro-cysts, and healthy babies can be delivered by in vitro fertilization and frozen embryo transfer following adequate control of multiple hormonal imbalances. Treatment may be complicated with adverse effects on drug metabolism caused by POR mutations. Unique challenges occur in female PORD patients such as ovarian macro-cysts prone to spontaneous rupture, masculinized genitalia without progression after birth, more frequently affected pubertal development, and impaired fertility. Thus, this review focuses only on 46, XX PORD patients to summarize the potential molecular pathogenesis, differential diagnosis of classic and non-classic PORD, and tailoring therapy to maintain health, avoid severe complications, and promote fertility.
Topics: Female; Pregnancy; Humans; Adrenal Hyperplasia, Congenital; Antley-Bixler Syndrome Phenotype; Rupture, Spontaneous; Karyotype; Disorders of Sex Development; Cysts
PubMed: 37635957
DOI: 10.3389/fendo.2023.1226387 -
JBRA Assisted Reproduction Oct 2020We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid... (Review)
Review
We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2% among the world's female population, with profound repercussions on gestation and fetal formation. During the gestational period, the thyroid is initially stimulated by high concentrations of human chorionic gonadotrophin; thus, maintaining maternal euthyroidism during pregnancy and lactation is fundamental for fetal growth and development. Besides, the hormones produced by this gland are involved in the formation of various organs, such as the skin, brain and gonads. Hypothyroidism is associated with several menstrual abnormalities, anovulation and hyperprolactinemia, resulting in a high rate of abortions, premature births, placental rupture, and weight-related neonatal deficits. In addition, there are studies showing that hypothyroidism can affect ovarian morphology (number of ovarian follicles) and testicular morphology (changes in the testicular-lumen epithelium). Melatonin is a hormone known to modulate the estrous cycle and pregnancy, and studies show that the exogenous application of melatonin increased T4 levels in female rats and controlled the decrease in T3 serum levels, reverting the sigs of hypothyroidism.
Topics: Animals; Female; Hypothyroidism; Male; Melatonin; Ovary; Rats; Testis
PubMed: 32945645
DOI: 10.5935/1518-0557.20200053