Ovarian Biomechanics: From Health to Disease

Biomechanics is a physical phenomenon which mainly related with deformation and movement of life forms. As a mechanical signal, it participates in the growth and development of many tissues and organs, including ovary. Mechanical signals not only participate in multiple processes in the ovary but also play a critical role in ovarian growth and normal physiological functions. Additionally, the involvement of mechanical signals has been found in ovarian cancer and other ovarian diseases, prompting us to focus on the roles of mechanical signals in the process of ovarian health to disease. This review mainly discusses the effects and signal transduction of biomechanics (including elastic force, shear force, compressive stress and tensile stress) in ovarian development as a regulatory signal, as well as in the pathological process of normal ovarian diseases and cancer. This review also aims to provide new research ideas for the further research and treatment of ovarian-related diseases.

Early Warning for Ovarian Diseases Based on Plasma Non-esterified Fatty Acid and Calcium Concentrations in Dairy Cows

Inactive ovaries (IO) and ovarian (follicular or luteal) cysts (FC or LC) are two common ovarian diseases leading to infertility in dairy cattle. Both disorders are associated with altered metabolites and hormones. There are currently no known effective biomarkers that can be used for early diagnosis of ovarian diseases. The purpose of this study was to identify the plasma biomarkers of ovarian diseases in Holstein dairy cows that facilitate an early diagnosis of the diseases and control its progression. The experiment was performed from 3 weeks postpartum and last for 7 weeks. Seventy-six multiparous Holstein cows (mean age, 4.36 years; weight, 635.63 kg) were divided into healthy control group (HC, n = 22), FC group (n = 18), LC group (n = 18) and IO group (n = 18) by rectal palpation or ultrasonography during the last 2 weeks before trial end. Blood was collected via tail vein for measurement of plasma energy metabolites, liver function indicators, minerals, and hormones at 3 and 8 weeks postpartum. Data were analyzed by Mann-Whitney U, Kruskal-Wallis, Spearman correlation, binary logistic regression analysis and receiver operating characteristic analysis, where applicable. At 8 weeks postpartum, FC cows had a more severe body condition score loss and these had greater levels of non-esterified fatty acids (NEFA) and estradiol, and lesser levels of alanine aminotransferase (ALT), progesterone and insulin-like growth factor 1 (IGF-1) levels than HC cows (P < 0.05). LC cows had a lower milk yield, higher NEFA and progesterone levels, and lower calcium, phosphorus and magnesium levels than HC cows (P < 0.05). IO cows had a lower body condition score, higher NEFA levels, and lower ALT, calcium, phosphorus, magnesium, estradiol, progesterone and IGF-1 levels than HC cows (P < 0.05). At 3 weeks postpartum, cows with ovarian diseases had greater (P < 0.05) concentrations of NEFA, and lesser concentrations of ALT, calcium, phosphorus and IGF-1 than HC cows. Early warning values for ovarian diseases were plasma NEFA concentrations >0.50 mmol/L, or calcium concentrations <2.02 mmol/L. Therefore, plasma NEFA and calcium could be used as early-warning indicators for ovarian diseases in dairy cows.

Computed tomography of the uterus and ovaries in healthy dogs: a descriptive and comparative study

Canine uterine and ovarian diseases are common in countries where prophylactic ovariohysterectomy is not generally performed and clinical work-up is commonly confined to ultrasonography of the female reproductive tract. Although increasingly used in veterinary practice, there is a lack of computed tomography (CT) data on either the normal or abnormal appearance of these organs. In this prospective, descriptive and comparative study, CT images of the uterus and ovaries of 22 bitches with no clinical signs of reproductive organ disease were examined. CT was compared to ultrasonography and the level of agreement between both was analyzed. The results indicate that it is feasible to evaluate the entire uterus and ovaries using CT. In this study, a range of cervical, uterine horn and ovarian appearances are described and illustrated. Although native CT failed to detect uterine cystic lesions, other CT characteristics were linked to cystic endometrial hyperplasia, warranting ultrasonographic examination. In general, CT can be used to approximate ultrasonographic measurements.

68Ga-DOTA-FAPI-04 PET/CT as a Promising Tool for Differentiating Ovarian Physiological Uptake: Preliminary Experience of Comparative Analysis With 18F-FDG

Objectives: This study aimed to investigate the physiological distribution characteristics of 68Ga-DOTA-FAPI-04 in the ovary, and assess the feasibility of early diagnosis of primary ovarian disease with 68Ga-DOTA-FAPI-04 PET/CT.Methods: We retrospectively analyzed the data of patients who received 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT scanning in the Nuclear Medicine Department of our hospital within 3 days from September 2020 to January 2021. We selected the data in which ovaries showed abnormal FDG activity. Patients with abnormal ovarian FDG uptake with focus confirmed by pathological biopsy or clinical follow-up as pathological changes were excluded. The uptake of tracers (18F-FDG and 68Ga-FAPI) was semi-quantitatively analyzed.Results: This study included 14 patients (average age was 38.6). Physiological ovarian uptake was mostly unilateral, and there was no significant difference in SUVmax between the left and right sides (FDGt = 0.272, FAPIt = 0.592). The ovary SUVmax of FDG (4.89 ± 1.84) was statistically significantly higher than that of FAPI (1.53 ± 0.37). The Le/Li ratio on FDG is 3.38 ± 1.81, TBR is 5.81 ± 1.98, while the Le/Li ratio on FAPI is 3.57 ± 1.26, TBR is 0.94 ± 0.19.Conclusion: Our research shows that ovarian functional or pathological changes can be manifested as FDG avid, while 68Ga-DOTA-FAPI-04 has no physiological accumulation in the ovary and is not affected by the menstrual cycle. Therefore, 68Ga-DOTA-FAPI-04 has unique advantages in the diagnosis of ovarian diseases, and can identify them early and accurately.

Observational study on serum markers and circulating tumor cells in ovarian cancer

1) To detect Cyclophilin, APC and SFRP5 genes associated with Epithelial ovarian cancer by PCR. 2) To study and compare the prognostic and diagnostic efficacy of serological markers like Ca 125 and HE4 and their correlation with epithelial/ non epithelial ovarian neoplasms.Comparative observational study, Prospective study 64 cases fulfilling the inclusion criteria and giving their consent for inclusion in the study were enrolled as subjects of the present study over a period of one year. After DNA extraction (Invitrogen mini kit, USA) conventional PCR to amplify the extracted DNA and further subjected them to agarose gel electrophoresis for the identification(expression) of 3 genes i.e Cyclophillin, APC and SFRP5, was done; However, none expressed.ELISA was used to assess CA125 and HE4 pre and post surgical intervention. The serum markers were raised more in malignant epithelial ovarian cancer cases and levels plummeted after surgical intervention, as compared to benign masses. We could not establish correlation of the genes’ expression with the serum markers and histopathology. Combining HE4 and CA125 both might be more helpful than either of them using alone, in diagnosing as well as prognosticating ovarian diseases. A panel of multiple genes on a larger sample size may be needed for CTC detection.Early detection of ovarian tumors leads to early diagnosis and hence early institution of intervention and hence decreased morbidity and mortality.

Potential Health Benefits of Curcumin on Female Reproductive Disorders: A Review

Curcumin is one of the main polyphenolic compounds in the turmeric rhizome. It possesses antioxidant, anti-inflammatory, anti-cancer, anti-arthritis, anti-asthmatic, anti-microbial, anti-viral and anti-fungal properties. This review aims to provide an overview of the potential health benefits of curcumin to treat female reproductive disorders, including polycystic ovary syndrome (PCOS), ovarian failure and endometriosis. Comprehensive information on curcumin was retrieved from electronic databases, which were MEDLINE via EBSCOhost, Scopus and Google Scholar. The available evidence showed that curcumin reduced the high level of androgen in PCOS. Studies in rodents suggest that curcumin resulted in the disappearance of cysts and the appearance of healthy follicles and corpora lutea. Furthermore, animal studies showed curcumin improved the overall function of the ovary in ovarian diseases and reversed the disturbance in oxidative stress parameters. Meanwhile, in vitro and in vivo studies reported the positive effects of curcumin in alleviating endometriosis through anti-inflammatory, anti-proliferative, anti-angiogenic and pro-apoptotic mechanisms. Thus, curcumin possesses various effects on PCOS, ovarian diseases and endometriosis. Some studies found considerable therapeutic effects, whereas others found no effect. However, none of the investigations found curcumin to be harmful. Curcumin clinical trials in endometriosis and ovarian illness are still scarce; thus, future studies need to be conducted to confirm the safety and efficacy of curcumin before it could be offered as a complementary therapy agent.

O-082 The ratio AMH/antral follicle count varies according to the etiologies of diminished ovarian reserve suggesting differences in follicular health

Study question Does diminished ovarian reserve (DOR) and its etiology impact the AMH/AFC ratio? Summary answer AMH/AFC ratio varies according to the etiology of DOR in young women, suggesting different impact on the follicular health, and further oocyte quality. What is known already Anti-Müllerian hormone and antral follicle count currently represent the two most accurate markers of the follicular ovarian status. Even though they may diagnose a reduction in the follicular stockpile, low values remain inefficient for predicting poor oocyte quality, in particular in young women. Since AMH is produced by the granulosa cells of follicles ranging from primary to small antral follicles, we hypothesized that the etiology of diminished ovarian reserve might differently impact the follicular health and their capacity of producing this peptide. Study design, size, duration From November 2018 to December 2021, we conducted a monocentric, retrospective study including a total of 484 infertile patients < 37 years with DOR. Participants/materials, setting, methods All patients underwent measurement of AMH levels and AFC. DOR was diagnosed according to the Bologna criteria (AMH < 1.1 ng/mL and AFC < 7). AMH/AFC ratio was compared to values obtained in 154 tubal or male infertility patients matched for age and BMI, with AMH and AFC in the normal ranges. This ratio was studied according to the etiology of DOR: genetic (n = 26), post-chemotherapy (n = 102), idiopathic (n = 215) or ovarian diseases (ovarian cyst or history of ovarian surgery, n = 141). Main results and the role of chance Overall, median age of women with DOR was 30 (18-37) years. As expected, age and BMI were comparable in women with DOR and those having normal ovarian reserve tests. In addition, the AMH/AFC ratio failed to show any difference between these 2 groups (0.143 ± 0.22 vs. 0.166 ± 0.11, NS, respectively). Among women with DOR, the etiology was significantly associated with different AMH/AFC ratio. Indeed, patient with DOR of surgical origin (ovarian diseases group) displayed higher mean values (0.283 ± 0.32 ng/mL/ Foll) when compared with those included in genetic (0.079 ± 0.15 ng/mL/ Foll, p < 0.01), idiopathic (0.103 ± 0.16 ng/mL/ Foll, p < 0.03) or post-chemotherapy (0.084 ± 0.20 ng/mL/ Foll, p < 0.01) groups. Moreover, genetic and post-chemotherapy DOR was also associated with lower AMH/AFC ratio in comparison with idiopathic DOR. Limitations, reasons for caution Despite interesting results, the retrospective nature of the present study may represent a limitation. Moreover, AMH/AFC ratio constitute an indirect method for assessing per follicle AMH production. We hypothesized that this ratio might reflect the follicular health. Its impact on natural conception and assisted reproductive technologies outcome is not known. Wider implications of the findings AMH/AFC ratio may represent an innovative tool aiming to indirectly assess follicular health and possibly oocyte quality in young women with DOR. The etiology of DOR differently impacts the follicular function as reflected by AMH/AFC ratio. Further data on live birth rates following natural or medically assisted pregnancies is needed. Trial registration number N/A

Explaining Ovarian Cancer Gene Expression Profiles with Fuzzy Rules and Genetic Algorithms

The analysis of gene expression data is a complex task, and many tools and pipelines are available to handle big sequencing datasets for case-control (bivariate) studies. In some cases, such as pilot or exploratory studies, the researcher needs to compare more than two groups of samples consisting of a few replicates. Both standard statistical bioinformatic pipelines and innovative deep learning models are unsuitable for extracting interpretable patterns and information from such datasets. In this work, we apply a combination of fuzzy rule systems and genetic algorithms to analyze a dataset composed of 21 samples and 6 classes, useful for approaching the study of expression profiles in ovarian cancer, compared to other ovarian diseases. The proposed method is capable of performing a feature selection among genes that is guided by the genetic algorithm, and of building a set of if-then rules that explain how classes can be distinguished by observing changes in the expression of selected genes. After testing several parameters, the final model consists of 10 genes involved in the molecular pathways of cancer and 10 rules that correctly classify all samples.

Human artificial oocytes from patients’ somatic cells: past, present and future

The first attempts at generating functional human oocytes by using the transfer of patients’ somatic cell nuclei, as DNA source, into donor enucleated oocytes date back to the early 2000s. After initial attempts, that gave rather encouraging results, the technique was abandoned because of adverse results with this technique in the mouse model. Priority was then given to the use of induced pluripotent stem (iPS) cells, based on excellent results in the mouse, where mature oocytes and live healthy offspring were achieved. However, these results could not be reproduced in humans, and oogenesis with human iPS cells did not continue beyond the stage of oogonium. These data suggest that the use of enucleated donor oocytes will be necessary to achieve fertilizable human oocytes with somatic cell-derived DNA. The main problem of all these techniques is that they have to meet with two, sometimes contradictory, requirements: the haploidization of somatic cell-derived DNA, on the one hand, and the remodeling/reprogramming of DNA of somatic cell origin, so as to be capable of supporting all stages of preimplantation and postimplantation development and to give rise to all cell types of the future organism. Further research is needed to determine the optimal strategy to cope with these two requirements. Lay summary The recourse to artificial oocytes, generated by using the patient’s own DNA derived from cells of somatic origin, represents the ultimate opportunity for women who lack healthy oocytes of their own but yearn for genetically related offspring. Many different pathologies, such as ovarian cancer, premature ovarian failure, other ovarian diseases and natural, age-related ovarian decay can cause the absence of available oocytes. The demand for artificial oocytes is increasing continuously, mainly because of the tendency to postpone maternity to still more advanced ages, when the quantity and quality of oocytes is low. This minireview focuses on the generation of artificial oocytes using different strategies and scenarios, based on the accumulated experience in humans and experimental animals.

Validation of IOTA-ADNEX Model in Discriminating Characteristics of Adnexal Masses: A Comparison with Subjective Assessment

(1) Background: The aim of this study is to compare the IOTA-ADNEX (international ovarian tumor analysis–assessment of different neoplasias in the adnexa) model with gynecologic experts in differentiating ovarian diseases. (2) Methods: All participants in this prospective study underwent ultrasonography (US) equipped with the IOTA-ADNEXTM model and subjective assessment by a sonographic expert. Receiver operating characteristic (ROC) curves were also generated to compare overall accuracies. The optimal cut-off value of the ADNEX model for excluding benign diseases was calculated. (3) Results: Fifty-nine participants were eligible: 54 and 5 underwent surgery and follow-up computed tomography (CT), respectively. Benign and malignant diseases were confirmed in 49 (83.1%) and 10 (16.9%) participants, respectively. The specificity of the ADNEX model was 0.816 (95% confidence interval (CI): 0.680–0.912) in all participants and 0.795 (95% CI, 0.647–0.902) in the surgical group. The area under the ROC curve of the ADNEX model (0.924) was not significantly different from that of subjective assessment (0.953 in all participants, 0.951 in the surgical group; p = 0.391 in all participants, p = 0.407 in the surgical group). The optimal cut-off point using the ADNEX model was 47.3%, with a specificity of 0.977 (95% CI: 0.880–0.999). (4) Conclusions: The IOTA-ADNEX model is equal to gynecologic US experts in excluding benign ovarian tumors. Subsequently, being familiar with this US software may help gynecologic beginners to reduce unnecessary surgery.