Stage Ovarian Cancer Research Articles

MALIGNANT STRUMA OVARII (KASUS LANGKA)

Struma ovarii (SO) are rare and accur in 2-3% of mature ovarian teratomas, most SO cases are benign. Malignant struma ovarii (MSO) is even more rare and occurs in 0,5- 5% of all cases, with the most common histologies identified are papillary and follicular carcinoma, most commonly affect patients in their 4th to 6th decade of life. Due to the rarity of malignant transformation, data about its management are lacking. A 49-years-old woman P2A0 with abdominal pain and pelvic mass, admitted for a hysterectomy and bilateral salpingo-oophorectomy. The left ovary was measured 13x11x5 cm, cystic and partly solid, filled with gelatinous fluid, composed of thyroid follicles with the appearance of "ground glass", "nuclear inclusion" and "nuclear groove", forming a papillifer structure. The diagnostic of MSO is based on histological features include cellular atypia, increased hyperplasia, nuclear pleomorphism, mitotic activity, vascular and/or capsular invasion. To be classified as a MSO, teratoma containing 50% or more thyroid tissue. MSO necessitates surgical staging for ovarian cancer with pelvic washings, total abdominal hysterectomy, bilateral salpingo- oophorectomy, lymph node sampling, total thyroidectomy, and radioactive I-131 ablation. Based on the clinical examination and histopatological examination the patient was diagnosed with MSO (ICD O: 9090/3).

Function Analysis of Cholesterol 7-Desaturase in Ovarian Maturation and Molting in Macrobrachium nipponense: Providing Evidence for Reproductive Molting Progress.

The Cholesterol 7-desaturase gene plays an important role in insect ecdysone synthesis, but its role in ovarian development has not been reported. In this study, characteristics and the phylogenetic relationship of Cholesterol 7-desaturase were identified by bioinformatics. qPCR showed that the Mn-CH7D gene was highly expressed in the ovary, which was much higher than that in other tissues, and the expression level of Mn-CH7D reached the highest level at the third stage of the ovarian development stage (O-III). During embryonic development, the Mn-CH7D gene expression was highest in the zoea stage. The function of the Mn-CH7D gene was explored by RNA interference. The experimental group was injected with Mn-CH7D dsRNA through the pericardial cavity of M. nipponense, while the control group was injected with the same volume of dsGFP. Statistical analysis of gonadal development and GSI calculation showed that the silencing of Mn-CH7D resulted in the suppression of gonadal development. In addition, the molting frequency of the experimental group was significantly lower than that of the control group during the second molting cycle after silencing Mn-CH7D. On the seventh day after silencing, ecdysone content in the experimental group was significantly reduced. These results demonstrated that the Mn-CH7D gene played a dual role in ovarian maturation and molting of M. nipponense.

The Role of Psychological Distress in the Relationship between Personality Dimensions and Pregnancy Outcome of Women Undergoing Assisted Reproductive Treatment (IVF/ICSI).

Objective: The aim of this study was to determine the role played by psychological distress in the relation between personality dimensions and pregnancy outcome of women undergoing in vitro fertilization/Intra-Cytoplasmic Injections (IVF/ICSI) treatment. Method : This prospective cohort study was conducted for 12 months on 154 infertile women who were receiving IVF/ICSI assisted reproductive treatment for the first time. Research instruments for measuring psychological distress included the Fertility Problem Inventory (FPI) and the Depression, Anxiety, and Stress Scale (DASS-21). One of these was completed prior to ovarian stimulation and the other during the embryo transfer stage. The temperament and Character Inventory-Revised (TCI-R 125) was employed once to assess personality dimensions prior to the ovarian stimulation stage. Independent t-test, Mann Whitney test, Repeated Measures and path analysis were performed for statistical analysis of data. Results: The results of this study showed no significant difference between the pregnant and non-pregnant groups in personality traits (Harm avoidance and self-directness) and psychological distress (FPI and DASS scores). Repeated measures showed a significant difference in stress, anxiety, and depression levels between the two stages of ovarian stimulation and embryo transfer (P < 0.01). Path analysis showed no significant direct and indirect effect for harm avoidance on the pregnancy outcome when psychological distress was mediated. Conclusion: The effect of psychological factors on IVF outcomes is more complicated than is generally assumed and more studies are mandatory to clarify the relationship between personality traits and infertility treatments.

Abstract 5396: Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer

Abstract Introduction: Ovarian cancer (OC) is the second most common gynecologic cancer in the U.S, and is the deadliest cancer of the female reproductive system. Because of the complex nature of OC, diagnoses are often by display of symptoms at late stages of disease. Identifying OC at early stages can increase the 5-year survival rate from 40% in stage IV to 94% in stage I. Therefore, effective screening and detection of OC at early stages is imperative. The main objective of this study is to develop a diagnostic panel of markers that correlate with early-stage OC, and ultimately, improve the survival rate of patients. Background: Approaches in the past several years to detect malignant OC have focused on processing relevant images or screening genomic data. These studies use liquid-based biopsies, sonographic images, cyst images, CT images, MR imaging and genomics data. Some studies have focused on distinguishing malignant tumors versus benign tumor cells. In addition to statistical methods to examine available genomic datasets, Machine Learning models including K-Nearest Neighbor, K-means, Convolutional Neural Networks, Deep Learning, Support Vector Machine, Random Forest, and Fuzzy algorithms have been used. Methods: In this study we proposed a method to determine a possible correlation between some actively expressed genes and OC, using publicly available mRNA data sets. The samples were retrieved from the GSE106817 dataset via the NCBI GEO site, with 333 cancerous and 2759 Non-cancerous samples. The objective is to define a set of genes which is able to illustrate prediction of correlation through the use of PCA, NMF and SVD. We further verified our findings by testing on one additional different mRNA datasets. For this, we compared several machine learning algorithms to potentially correlate active genes and OC stages, from the available data. Results and Discussions: Through our study we have developed Machine Learning models valuable to identify patterns of disease at different stages, thus, potentially be useful in developing predictive models. Our initial experimental results have been demonstrated with a set of mRNA signatures, which may be used to create a panel of biomarkers valuable for detecting early-stage OC. Our results confirm the correlation between OC and PAX8, PEG3, and BIRC5, and MYB and RAC2. Continuation of this study highlights methods towards the early detection of OC and to improve disease identification outcome. Citation Format: Zahra Saghaie, Christine Richardson, M. Taghi Mostafavi. Early detection of ovarian cancer using mRNA sample data to investigate the correlation of specific gene mutations with ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5396.

Tregs are involved in VEGFA/ VASH1-related angiogenesis pathway in ovarian cancer

Vasohibin1 (VASH1) is a kind of vasopressor, produced by negative feedback from vascular endothelial growth factor A (VEGFA). Anti-angiogenic therapy targeting VEGFA is currently the first-line treatment for advanced ovarian cancer (OC), but there are still many adverse effects. Regulatory T cells (Tregs) are the main lymphocytes mediating immune escape function in the tumor microenvironment (TME) and have been reported to influence the function of VEGFA. However, whether Tregs are associated with VASH1 and angiogenesis in TME in OC is unclear. We aimed to explore the relationship between angiogenesis and immunosuppression in the TME of OC. We validated the relationship between VEGFA, VASH1, and angiogenesis in ovarian cancer and their prognostic implications. The infiltration level of Tregs and its marker forkhead box protein 3 (FOXP3) were explored in relation to angiogenesis-related molecules. The results showed that VEGFA and VASH1 were associated with clinicopathological stage, microvessel density and poor prognosis of ovarian cancer. Both VEGFA and VASH1 expression were associated with angiogenic pathways and there was a positive correlation between VEGFA and VASH1 expression. Tregs correlated with angiogenesis-related molecules and indicated that high FOXP3 expression is harmful to the prognosis. Gene set enrichment analysis (GSEA) predicted that angiogenesis, IL6/JAK/STAT3 signaling, PI3K/AKT/mTOR signaling, TGF-β signaling, and TNF-α signaling via NF-κB may be common pathways for VEGFA, VASH1, and Tregs to be involved in the development of OC. These findings suggest that Tregs may be involved in the regulation of tumor angiogenesis through VEGFA and VASH1, providing new ideas for synergistic anti-angiogenic therapy and immunotherapy in OC.

Low estradiol production of non-laying whooping cranes (Grus americana) is associated with the failure of small follicles to enter follicular hierarchy

For endangered species managed ex situ, production of offspring is a key factor to ensure healthy and self-sustaining populations. However, current breeding goals for the whooping crane (Grus americana) are impeded by poor reproduction. Our study sought to better understand mechanisms regulating ovarian function in ex situ managed whooping cranes and the regulatory function of the hypothalamic-pituitary–gonadal (HPG) axis in relation to follicle formation and egg laying. To characterize hormonal regulation of follicular development and ovulation, we collected weekly blood samples from six female whooping cranes during two breeding seasons, for a total of 11 reproductive cycles. The plasma samples were assessed for follicle stimulating hormone, luteinizing hormone, estradiol, and progesterone and the yolk precursors vitellogenin and very low-density lipoprotein. Ultrasonographic examination of the ovary was conducted at the time of blood collection. Preovulatory follicles (>12 mm) were present in laying cycles (n = 6) but absent in non-laying cycles (n = 5). The patterns of plasma hormone and yolk precursor concentrations corresponded to the stage of follicle development. Specifically, gonadotropin and yolk precursor concentrations increased as follicles transitioned from the non-yolky to yolky stage but did not increase further as the follicle advanced to preovulatory and ovulatory stages. Estrogen and progesterone concentrations increased as follicle size increased and reached peak concentrations (P < 0.05) when follicles developed to ovulatory and preovulatory stages, respectively. While overall mean circulating gonadotropin, progesterone, and yolk precursor concentrations did not differ for laying versus non-laying cycles, mean plasma estradiol in laying cycles was significantly higher than that in non-laying cycles. In summary, the findings suggested that disruption of mechanisms regulating follicle recruitment is likely responsible for the oviposition failure of the captive female whooping crane.

The potential role of the KFG and KITLG proteins in preventing granulosa cell apoptosis in Bubalus bubalis

BackgroundThe dynamics of mammalian follicular development and atresia is an intricate process involving the cell-cell communication mediated by secreted ovarian factors. These interactions are critical for oocyte development and regulation of follicular atresia which in part are mediated by keratinocyte growth factor (KGF) and kit ligand (KITLG), but their roles in the regulation of apoptosis in buffalo granulosa cells have not yet been defined. During mammalian follicular development, granulosa cell apoptosis triggers the atresia so ~ 1% follicles reach the ovulation stage. In the present study, we used buffalo granulosa cells to examine the effects of KGF and KITLG in apoptosis regulation and investigated potential mechanism on Fas-FasL and Bcl-2 signaling pathways. ResultIsolated buffalo granulosa cells were cultured with KGF and KITLG proteins using different doses (0, 10, 20, and 50 ng/ml) independently or in combination. Expression analysis for both anti-apoptotic (Bcl-2, Bcl-xL, and cFLIP) and pro-apoptotic (Bax, Fas, and FasL) genes at transcriptional levels were carried out by real-time PCR. Upon treatments, expression levels of anti-apoptotic genes were significantly upregulated in a dose-dependent manner, showing an upregulation at 50 ng/ml (independently), and at 10 ng/ml in combination. Additionally, upregulation of growth-promoting factors, bFGF, and α-Inhibin was also observed. ConclusionsOur findings suggest the potential roles of KGF and KITLG in determining granulosa cell growth and regulating apoptosis.

Combined effects of climate change and environmentally relevant mixtures of endocrine disrupting compounds on the fitness and gonads' maturation dynamics of Nucella lapillus (Gastropoda)

Coastal areas are affected by multiple stressors like climate change and endocrine disruptors (EDCs). In the laboratory, we investigated the combined effects of increased temperature and EDCs (drospirenone and mercury) on the fitness and gonads' maturation dynamics of the marine gastropod Nucella lapillus for 21 days.Survival was negatively affected by all the stressors alone, while, in combination, a synergistic negative effect was observed.Both chemicals, as single factors, did not cause any effect on the maturation stage of ovaries and testis. However, in the presence of a higher temperature, it was clear a delay in the maturation stage of the ovaries, but not in the testis, suggesting a higher negative impact of the stressors in females than in males.In summary, drospirenone caused a low negative impact in aquatic species, like gastropods, but in combination with other EDCs and/or increased temperature can be a matter of concern.

Expression pattern analysis of anti-Mullerian hormone in testis development of pearlscale angelfish (Centropyge vrolikii).

In vertebrates, anti-Mullerian hormone (Amh) secreted by Sertoli cells (SC) performs a pivotal function in male sex differentiation. Compared with that of higher vertebrates, the expression pattern of Amh is more diversified in fish. In this study, the full-length complementary DNA (cDNA) of Amh in Centropyge vrolikii (Cv-Amh) was cloned and analysed, which was 2,470 bp, including a 238 bp 5'UTR, a 1,602 bp ORF and a 633 bp 3'UTR; the similarity of Amh between Cv-Amh and other fish is relatively high. The quantitative real-time PCR (qRT-PCR) results of healthy tissues and gonads at sex reversal stages in C. vrolikii showed that the expression level of Amh in the testis was significantly higher than that in other tissues (P < 0.05). Amh was weakly expressed in the vitellogenic stage ovary and perinucleolus stage ovary, but its expression significantly increased in the gonads at the hermaphroditic stage, and finally reached the highest in the pure testis after sexual reversal. The results of in situ hybridization indicated that the positive signal of Amh was strongly concentrated in SCs of testis. After Amh knockdown in the gonads, the effect on sex-related genes was tested using qRT-PCR. Among these, the expression of Dmrt1, Cyp11a, Hsd11b2, Sox8 and Sox9 significantly decreased, whereas that of Cyp19a, Sox4, Foxl2 and Sox3 increased. These results suggested that Amh could be the pivotal gene in reproductive regulation in C. vrolikii, and the data will contribute to sex-related research of C. vrolikii in the future.

Hepatopancreas Proteomic Analysis Reveals Key Proteins and Pathways in Regulatory of Ovary Maturation of Macrobrachium nipponense.

A TMT-based (Tandem Mass Tag) liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics approach was employed to explore differentially expressed proteins (DEPs) and KEGG pathways in hepatopancreas of 5 ovary stages. In total, 17,999 peptides were detected, among which 3395 proteins were identified. Further analysis revealed 26, 24, 37, and 308 DEPs in HE-I versus HE-II, HE-II versus HE-Ⅲ, HE-Ⅲ versus HE-Ⅳ, and HE-Ⅳ versus HE-Ⅴ, respectively (HE-I, HE-II, HE-III, HE-IV, and HE-V means hepatopancreas sampled from ovary stage I to V.). Gene ontology (GO) analysis indicated that DEPs were significantly enriched in "catalytic activity", "metabolic process", and "cell" of 4 comparison groups in turn. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that in hepatopancreas, as the ovaries developed to maturation, carbohydrate metabolism, lipid metabolism, amino acid metabolism, and lysosome played important roles in turn. The mRNA expression of 15 selected DEPs were consistent with proteome results by qPCR analysis. Further mRNA expression investigation results suggested 4 proteins (fatty acid-binding protein, NPC intracellular cholesterol transporter 1, Serine hydroxymethyltransferase, and Crustapin) were involved in ovary maturation. These results enhance the understanding of the regulatory role of hepatopancreas in M. nipponense ovary maturation and provide new insights for understanding the crustacean regulation mechanisms.

Reproduction system development of Ceracris kiangsu Tsai female adults and its relationship with fitness characteristics.

Research on the ovarian development of insect pests helps provide key information for predicting pest occurrences, and currently, there is very limited information about the reproductive system of Ceracris kiangsu Tsai. This study aimed to assess the reproductive fitness of 321 adult female insects by using traditional methods to dissect female adults, measure female ovaries, and assess the process of egg formation. The phenotypic traits including body weight and body length were also measured and used to estimate the model of ovarian developmental stages. Four ovarian developmental stages before the oviposition were identified, and the fundamental ovarian structure of C. kiangsu displayed red dots on the matured eggs inside the calyx at ovarian developmental stage V. The accessory glands of C. kiangsu had the deepest folds at stage Ⅲ. Redundancy analysis (RDA) was used to explore the correlation between ovarian development, body weight, and body length. A significant positive correlation was observed for body weight (p = 0.001) and body length (p = 0.009), which varied with the grade of ovarian development evaluated by the ovarian developmental stage, ovarian length, ovarian width, and ovarian cross-sectional area. A partial least square (PLS) regression was used to model the ovarian developmental stage, with a stage-based PLS being identified as the more effective method, which was y = 1.509x 1 + 0.114x 2. The model provides a potentially rapid way to identify the population source as either "native" or "immigrant" from the phenotypic traits without dissection. The aforementioned model may be used to estimate adult emergence periods and identify migratory populations from their ovarian development, potentially aiding in implementing proper prevention measures.

An Evaluation of Effectiveness of a Texture Feature Based Computerized Diagnostic Model in Classifying the Ovarian Cyst as Benign and Malignant from Static 2D B-Mode Ultrasound Images.

To develop a computerized diagnostic model to characterize the ovarian cyst at its early stage in order to avoid unnecessary biopsy and patient anxiety. The main cause of mortality and infertility in women is ovarian cancer. It is very difficult to diagnose ovarian cancer using ultrasonography as benign and malignant ovarian masses or cysts exhibit similar characteristics. Early prediction and characterization of ovarian masses will reduce the unwanted growth of the ovarian mass. Transvaginal 2D B mode ovarian mass ultrasound images were preprocessed initially to enhance the image quality. And then, the region of interest (ROI) in this case ovarian cyst was segmented. Finally, Local Binary Pattern (LBP) textural features were extracted. A Support Vector Machine was trained to classify the ovarian cyst or mass as benign or malignant. The performance of the SVM improved with an average accuracy of 92% when the textural features were extracted from the Original Gray Value-based LBP (OGV-LBP) image than the histogram- based LBP. The SVM can classify the transvaginal 2D B mode ovarian cyst ultrasound images into benign and malignant effectively when the textural features from the original gray value-based LBP extracted were considered.

Detection and Genotyping of Human Papillomavirus (HPV16/18), Epstein–Barr Virus (EBV), and Human Cytomegalovirus (HCMV) in Endometrial Endometroid and Ovarian Cancers

The purpose of this study was to evaluate the relationship between human papillomavirus (HPV16/18), Epstein-Barr virus (EBV), and human cytomegalovirus (HCMV) infections and the occurrence of ovarian cancer in 48 women, of whom 36 underwent surgery and chemotherapy (group A), 12 in whom surgery was sufficient (group B), and 60 with endometroid endometrial cancer stage G1-G3 (group C), compared to patients in whom the uterus and its appendages were removed for nononcological reasons (control group). The detection of HPV, EBV, and HCMV in tumor tissue and normal tissue was performed using the real-time polymerase chain reaction (RT-PCR) technique. A statistically significantly higher risk of endometrial cancer was noted in patients infected only with HCMV (OR > 1; p < 0.05). In contrast, a significantly higher risk of ovarian cancer in group A was associated with HPV16, HPV18, and EBV (OR > 1; p < 0.05); a significantly higher risk of ovarian cancer in group B was associated with HPV18 and HMCV (OR > 1; p < 0.05). The obtained results suggest that HCMV infection is associated with the development of a stage of ovarian cancer when treatment can be completed with surgery alone. Meanwhile, EBV appears to be responsible for the development of ovarian cancer in more advanced stages.

Dynamics of extracellular vesicle-coupled microRNAs in equine follicular fluid associated with follicle selection and ovulation.

Innumerable similarities in reproductive cyclicity and hormonal alterations highlight the considerable utility of the mare to study aspects of follicular dynamics and reproductive function in view of the largely constricted, human research subjects. The bi-directional communication between the growing oocyte and the surrounding somatic cells embodies the hallmark of mammalian follicular development, partially mediated by extracellular vesicles (EVs) encapsulated with microRNAs (miRNAs) and present in the follicular fluid (FF). Here, we aimed to decipher the dynamics of the miRNAs in EVs from equine FF aspirated in vivo during different stages of follicular development, namely, predeviation (PreDev; 18-20 mm), deviation (Dev; 22-25 mm), postdeviation (PostDev; 26-29 mm), preovulatory (PreOV; 30-35 mm), and impending ovulation (IMP; ∼40 mm). Approximately 176 known miRNAs were found in all groups with 144 mutually detected among all groups. Cluster analysis exhibited 15 different expression patterns during follicular development. Among these patterns, a group of 22 miRNAs (including miR-146b-5p, miR-140, and miR-143) exhibited a sharp reduction in expression from the PreDev until the PreOV stage. Another cluster of 23 miRNAs (including miR-106b, miR-199a-5p, and miR-125a-5p) exhibited a stable expression pattern at the PreDev stage until the PostDev stage, with a significant increase at the PreOV stage followed by a significant decrease at the IMP stage. In conclusion, this study provides greater insights into the stage-specific expression dynamics of FF EV-miRNAs during equine follicular development, which may propose novel approaches to improve ART and provide new biomarkers to facilitate the assessment of ovarian pathophysiological conditions.

The vitellogenesis-inhibiting hormone (SpVIH) of the crab Scylla paramamosain is not likely to have a vitellogenesis-inhibiting function in the ovary

The function and molecular characterization of the previously reported crab (Scylla paramamosain) vitellogenesis inhibiting hormone SpVIH is still unclear. In this experiment, SpVIH’s bioinformatic and functional characterizations were analyzed. Sequence analysis showed SpVIH was clustered with several type II MIH/GIHs of the Brachyura. The expression of SpVIH in the eyestalk was low in the early ovarian developmental stage I and increased with the advancement of ovary maturation. Interestingly, the SpVIH transcript was still at a high level in the ovary of females at the middle to late maturation stage. SpVIH’s function was studied according to the expression of vitellogenin (Vg) and vitellogenin receptor (VgR) in the ovary and hepatopancreas after incubation with SpVIH-dsRNA and recombinant SpVIH protein (rSpVIH). In vitro assay results indicated that rSpVIH has a significant stimulative effect on the expression of Vg in the hepatopancreas in the middle stage of vitellogenesis and in the ovary of each vitellogenesis stage. However, SpVIH-dsRNA has no significant effect on the expression of Vg when SpVIH-dsRNA is introduced to the ovary and hepatopancreas at the early, middle, and late stages of vitellogenesis. Furthermore, the co-incubation experiment result indicated that the eyestalk consists of factor(s) that can significantly up-regulate the expression of Vg in the ovary, with a further combination of dsVIH and eyestalk under incubation, the significant increase of Vg-mRNA expression levels were also found in the ovary of four ovarian development stages of S. paramamosain. Contrary to the previous reports, SpVIH does not possess a vitellogenesis-inhibiting function but can promote vitellogenesis in the ovary and hepatopancreas.

Selection of Reference Gene for Expression Studies in the Ovary and Pituitary of Spotted Scat (Scatophagus argus) at Different Ovarian Stages

The spotted scat (Scatophagus argus) is the most widely commercially cultured fish in eastern and southern Asia that possess potential economic value. However, up to date, there are no studies reported on the selection of suitable reference genes in this fish, which is crucial for guaranteeing accurate and reliable results in RT-qPCR analyses. This study aimed at screening the most stable reference genes in the ovary and pituitary at different ovarian stages, which is of great significance for further research on the reproductive regulation mechanism of female S. argus. In this study, we selected twenty-one genes as the candidate reference genes, including four genes in the ovary (EEF1A, ACTB, B2M, and HPRT1), and seventeen genes in the pituitary (B2M, APOA1, CGBA, RPLP0, GNRHR, GUSB, TBP, SLC25A5, RPL4, PLA1A, GAPDH, GNB2L1, CTFS, HPRT1, RPS2, TFRC, and TUBB4B). To analyze the stability of the potential reference genes, we first used four commonly used software, BestKeeper, GeNorm, NormFinder, and ΔCt, and then we established comprehensive rankings with ReFinder. The results indicate that RPL4 and GNB2L1, and EEF1A and HPRT1 were the most appropriate reference genes for the pituitary and ovary of S. argus, respectively, in the three developmental stages of the ovary. Additionally, GeNorm analysis suggested that for the accurate normalization of gene expression, two reference genes were reliable in the ovary and pituitary of S. argus. To the best of our knowledge and understanding, this is the first study to identify appropriate reference genes for analyzing gene expression in S. argus. Consequently, this study can be used as a foundation for future research on the reproduction of S. argus.

The interplay between ovarian cancer and social relationships: an analysis of patients’ metaphors

Objective Research showed that ovarian cancer poses unique challenges to patients’ care experiences and that patients’ social networks could affect their care path significantly. The present study aimed to analyse the metaphors that patients used to signify the impact of the illness on their social relationships and the role of relationships in dealing with cancer. Design Following a qualitative description approach we conducted 38 semi-structured interviews with Australian (14) and Italian (24) women diagnosed at different stages of ovarian cancer. Results The analysis identified four themes bringing together the meanings expressed by participants’ metaphors: Lack of comprehension and communication; Isolation, marginalisation, and self-isolation; Discrepancy between the private and public self; and Social relationships as empowerment resources. Conclusion The polysemic nature of patients’ metaphors captures both the empowering and especially disempowering role of social relationships in dealing with ovarian cancer. Results also show that metaphors are used to make sense of the impact of ovarian cancer on social relationships and to express different strategies for managing patients’ networks.

Embryonic benzophenone-3 exposure inhibited fertility in later-life female zebrafish and altered developmental morphology in offspring embryos.

Benzophenone-3 (BP3), an organic UV filter widely used in personal care products, is ubiquitous in aquatic environments. Previous studies have shown that BP3 can interfere with oocytes development in the ovary. The current study was conducted to evaluate the effects of embryonic BP3 exposure on reproductive outcomes in later life. Zebrafish embryos were exposed to different concentrations of BP3 (0, 1, 10, 100 μg/L) for 5 days in the developmental stage and subsequently fed for 4 months without any toxins. The body length, body weight, and ovary weight in F0 female adult zebrafish and morphology indices in F1 offspring embryos were measured. The reproductive behaviors of adult zebrafish were recorded by a digital camera. HE staining was used to estimate the development of oocytes and the proportion of different phases was calculated. qPCR was used to detect the expression levels of reproduction-related genes of the hypothalamic-pituitary-gonadal (HPG) axis. Our findings revealed that the body length and body weight were not changed with embryonic BP3 exposure, but BP3 exposure inhibited the development and maturation of ovaries in later-life female zebrafish, accompanied by an increased proportion of follicles in the primary growth and early vitellogenic stages, and a decline in the full-growth stage in ovaries. Meanwhile, reduced egg production, delayed hatching rate, altered somite count and increased mortality rate were observed at 100 μg/L in offspring embryos. Behavioral results showed that BP3 exposure reduced the frequency of chasing, touching, entering the spawning area, and the duration of fish entering the spawning area later in life, qPCR analysis showed that the expression levels of reproduction-related genes of the HPG axis were downregulated in females, following a decreasing trend in plasma E2 and 11-KT levels. These results suggested that embryonic BP3 exposure negatively affected the fertility of fish and the development of their offspring embryos, which may cause potential risks to aquatic ecosystems and human health.

Identification of the cyclooxygenase (COX) gene and its role in ovarian development and ovulation of the oriental river prawn Macrobrachium nipponense

Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of prostaglandins (PGs), which are involved in ovarian development and ovulation in crustaceans. In this study, complementary DNA (cDNA) of COX in Macrobrachium nipponense (MnCOX) was identified, and its function in ovarian development and ovulation was investigated by quantitative real-time PCR (qPCR), fluorescence in situ hybridization (FISH), RNA interference (RNAi) and arachidonic acid (AA), dexamethasone (DEX) and DEX+ prostaglandin E2 (PGE2) administration. The results showed that the complete cDNA of MnCOX is 3238 bp, including an 1848 bp open reading frame (ORF) that encodes 615 amino acids. The MnCOX protein conservatively possesses a membrane-binding domain, an epidermal growth factor-like (EGF-like) domain, an animal haem peroxide domain, three N-glycosylation sites and seven essential catalytic residues. The richest MnCOX transcript of nine tissues was found in the gill, followed by the ovary and intestine. In six ovarian development stages, the MnCOX transcript was the richest in the stage Ⅴ ovary. FISH showed that the MnCOX transcript was present in the cytoplasm of oocytes. MnCOX knockdown led to decreases in PGE2 content, expression levels of the vitellogenin (Vg) and vitellogenin receptor (Vgr) genes and the gonadsomatic index (GSI) of prawns. Moreover, oocyte development was delayed, and the oviposition rate and the number of eggs ovulated were reduced after MnCOX knockdown. AA administration increased the expression of MnCOX, PGE2 content and the oviposition rate of prawns. However, DEX administration decreased the expression of MnCOX, PGE2 content, oviposition rate, and the number of eggs ovulated by prawns. The addition of PGE2 to DEX injection rescued the negative effect of DEX on the ovulation of M. nipponense. This investigation illustrates that MnCOX plays an important role in regulating ovarian development and ovulation in M. nipponense by affecting the synthesis of PGs.

High production of transfer RNAs identifies the presence of developing oocytes in ovaries and intersex testes of teleost fish

5S rRNA is highly transcribed in fish oocytes and this transcription levels can be used to identify the presence of oocytes in the intersex testes of fish exposed to xenoestrogens. Similar to 5S rRNA, tRNAs are transcribed by RNA polymerase III (Pol-III) in eukaryotes, so this study focuses in the analysis of the levels of expression of tRNAs in the gonads (ovaries and testes) of eight teleost species as a possible new oocyte molecular marker. Total RNA extracted from gonads of six commercial teleost species in the Biscay Bay, from the pollution sentinel species thicklip grey mullet (Chelon labrosus) known present intersex testes in response to xenoestrogens in Gernika estuary and from the laboratory model species Danio rerio were analysed through capillary electrophoresis. Bioanalyzer electropherograms were used to quantify the concentrations of tRNAs, 5S and 5.8S rRNA. All studied ovaries expressed significantly higher levels of tRNAs and 5S rRNA than testes. A tRNA to 5.8S rRNA index was calculated which differentiates ovaries from testes, and identifies some intersex testes in between testes and ovaries in mullets. The tRNA/5.8S ratio was highest in ovaries in previtellogenic stage, decreasing towards maturity. Thus, strong oocyte expression of tRNAs is an additional proof of high activity levels of Pol-III during early stages of oocyte development in teleost ovaries. Incidentally, we observed that miRNA concentrations were always higher in testes than ovaries. The indexing approach developed in the present study could have multiple applications in teleost reproduction research and in the development of early molecular markers of intersex condition.