OBJECTIVES: To evaluate the protective effect of Lycium barbarum polysaccharides (LBP) against cisplatin-induced ovarian granulosa cell injury and investigate its possible mechanisms. METHODS: Human granulosa-like tumor cell line (KGN) were treated with 2.5 µg/mL cisplatin for 24 h, followed by treatment with 100, 500, and 1000 mg/L LBP, and the changes in cell viability, apoptosis, level of anti-Müllerian hormone (AMH), and cell ultrastructure were detected with CCK-8 assay, flow cytometry, ELISA and transmission electron microscopy. The cellular expressions of Bax, caspase-3, Bcl-2, and the PI3K/AKT pathway proteins were analyzed using Western blotting, and the expression of miR-23a was detected with RT-qPCR. KGN cell models with lentivirus-mediated miR-23a overexpression or knockdown were used to verify the therapeutic mechanism of LBP. RESULTS: Cisplatin treatment significantly inhibited cell viability, induced apoptosis, decreased AMH level, caused ultrastructural abnormalities, increased Bax and caspase-3 expression, and lowered Bcl-2 expression in KGN cells. Cisplatin also suppressed the activation of the PI3K/AKT signaling pathway and upregulated miR-23a expression in the cells. LBP intervention obviously alleviated cisplatin-induced injuries in KGN cells, and in particular, LBP treatment at the medium dose for 24 h significantly improved KGN cell viability, reduced apoptosis, enhanced their endocrine function, and ameliorated ultrastructural abnormalities. Mechanistically, medium-dose LBP obviously activated the PI3K/AKT pathway by downregulating miR-23a in cisplatin-treated cells, subsequently inhibiting Bax and caspase-3 while upregulating Bcl-2. Overexpression of miR-23a weakened while knockdown of miR-23a significantly enhanced the protective effects of LBP. CONCLUSIONS LBP alleviates cisplatin-induced apoptosis in KGN cells by inhibiting miR-23a expression and activating the PI3K/AKT pathway, suggesting a potential therapeutic strategy for ovarian function preservation.
Humans ; Cisplatin/adverse effects* ; MicroRNAs/genetics* ; Female ; Granulosa Cells/cytology* ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Down-Regulation ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Survival/drug effects*

Adult ; Female ; Humans ; Granulosa Cell Tumor/pathology* ; Prognosis ; Ovarian Neoplasms/pathology*

Female ; Gracilis Muscle ; Granulosa Cell Tumor ; Humans ; Muscle, Skeletal ; Ovarian Neoplasms ; Surgical Flaps ; Thigh

Gynandroblastoma is an extremely rare sex cord-stromal tumor with both female (granulosa cell tumor) and male (Sertoli-Leydig cell tumor) elements. Juvenile granulosa cell tumors are also very rare and are so named because they usually occur in children and adolescents. A 71-year-old woman with right upper quadrant abdominal pain visited our hospital. Pelvic computed tomography showed a large multilocular cystic mass, suspected to be of ovarian origin. We performed a total abdominal hysterectomy (total abdominal hysterectomy was performed) with bilateral salpingo-oophorectomy. A 13-cm multilocular cystic mass with serous fluid was observed in her right ovary. Upon microscopic examination, the solid component of the mass showed both Sertoli-Leydig cell and juvenile granulosa cell differentiation, which we diagnosed as gynandroblastoma. Gynandroblastoma with a juvenile granulosa cell tumor component is extremely rare and, until now, only six cases have been reported in the English literature. We report the first gynandroblastoma with a juvenile granulosa cell tumor component diagnosed in an elderly patient, along with a literature review.
Abdominal Pain ; Adolescent ; Aged ; Child ; Female ; Granulosa Cell Tumor ; Granulosa Cells ; Humans ; Hysterectomy ; Male ; Ovary ; Postmenopause ; Sex Cord-Gonadal Stromal Tumors

Adult ; Female ; Granulosa Cell Tumor ; metabolism ; pathology ; Humans ; Male ; Middle Aged ; Ovarian Neoplasms ; metabolism ; pathology

OBJECTIVE: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. METHODS: Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed. RESULTS: Most patients presented with abnormal genital bleeding including abnormal menstrual cycles. Eight of 16 patients older than 50 years had endometrial hyperplasia and one had endometrial cancer. Serum 17β-estradiol (E2) levels tended to be higher in patients over 50 years of age (p=0.081). Serum follicle-stimulating hormone (FSH) levels were low in all patients irrespective of serum E2 levels. Magnetic resonance imaging revealed a thicker endometrium in older as compared to younger patients (p<0.05). Tumor cells in the majority of cases were positive for inhibin α and P450 aromatase, irrespective of age and serum E2 levels. P450 17α-hydroxylase (P450c17) expression varied among cases. P450c17 was strongly positive in luteinized tumor cells and weakly positive in theca cells and fibroblasts. High E2 levels were associated with P450c17-positive cells in the tumor (p<0.05). CONCLUSION: The expression of hormone-synthesizing enzymes divides granulosa cell tumors into 2 distinct types; tumors with P450c17-positive cells show elevated serum E2 and related clinical symptoms, while tumors without these cells show symptoms related to FSH suppression by inhibin.
Adult* ; Aromatase ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometrium ; Estrogens ; Female ; Fibroblasts ; Follicle Stimulating Hormone ; Granulosa Cell Tumor* ; Granulosa Cells* ; Hemorrhage ; Humans ; Inhibins ; Lutein ; Magnetic Resonance Imaging ; Menstrual Cycle ; Ovary* ; Retrospective Studies* ; Steroid Hydroxylases ; Theca Cells

Opinions on ovariohysterectomy (OHE) of bitches vary depending on region and country. In this descriptive, prospective cross-sectional study, uterine tracts and ovaries exhibiting gross pathologic findings (n = 76) were collected post-surgery from a reference population of 3,600 bitches (2.11% incidence) that underwent elective OHE during September to November 2013 and evaluated by histopathology examination. Data were evaluated by using descriptive statistics and chi-squared tests. Bitches were of crossbred background with average age 5 years (range 0.6–8.0 years) and most were nulliparous (69.7%) with no anamnesis of reproductive diseases (81.6%). Frequencies of proestrus, estrus, and diestrus were 42.1%, 6.6%, and 19.7%, respectively. The presence of mammary gland masses (5.3%) significantly correlated with histopathologic findings in ovaries and age of the bitch (p < 0.05). Predominant uterine histopathologies included cystic endometrial hyperplasia, periglandular fibrosis, lymphoplasmocytary endometritis, and adenomyosis (19.7%, 14.5%, 4.0%, and 2.6%, respectively). In ovaries, hyperplasia of rete ovarii, follicular cysts, oophoritis, adenoma of the rete ovarii, cysts of superficial structures, and granulosa cell tumors (10.5%, 10.5%, 7.9%, 4.0%, 2.6%, and 2.6%, respectively) were observed. The results reveal the presence of subclinical pathologies in healthy bitches, suggesting that OHE at an early age is beneficial for prevention of reproductive pathologies.
Adenoma ; Adenomyosis ; Animals ; Cross-Sectional Studies* ; Diestrus ; Dogs* ; Endometrial Hyperplasia ; Endometritis ; Estrus ; Female ; Fibrosis ; Follicular Cyst ; Granulosa Cell Tumor ; Hyperplasia ; Mammary Glands, Human ; Oophoritis ; Ovary* ; Pathology ; Proestrus ; Prospective Studies ; Uterus*

Granulosa cell tumors (GCTs) are rare sex cord-stromal tumors that have been studied for decades. However, their infrequency has delayed efforts to research their etiology. Recently, mutations in human GCTs have been discovered, which has led to further research aimed at determining the molecular mechanisms underlying the disease. Mouse models have been important tools for studying GCTs, and have provided means to develop and improve diagnostics and therapeutics. Thus far, several genetically modified mouse models, along with one spontaneous mouse model, have been reported. This review summarizes the phenotypes of these mouse models and their applicability in elucidating the mechanisms of granulosa cell tumor development.
Animals ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Mice* ; Models, Animal ; Phenotype ; Sex Cord-Gonadal Stromal Tumors

No abstract available.
Granulosa Cell Tumor*

Adult granulosa cell tumors (AGCTs) presenting with massive ascites and elevated serum CA-125 levels have rarely been described in the literature. An ovarian mass, massive ascites, and elevated serum CA-125 levels in postmenopausal women generally suggest a malignant ovarian tumor, particularly advanced epithelial ovarian cancer. AGCT has low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography due to its low metabolic activity. In the present report, we describe a case of an AGCT with massive ascites, elevated serum CA-125 level, and low 18F-fluorodeoxyglucose uptake on positron emission tomography/computed tomography.
Adult* ; Ascites* ; Electrons* ; Female ; Granulosa Cell Tumor* ; Granulosa Cells* ; Humans ; Ovarian Neoplasms