The growth and development of follicles are regulated by genes,hormones and growth factors autocrined and paracrined from granulosa cells,theca cells,and oocytes.Products of glycolysis from granulosa cells such as pyruvate and lactate are one of the main energy sources,which play an important role during folliculogenesis and follicle maturity.Studies on the changes of the products and rate-limiting enzymes during granulosa cells' glycolysis help to clarify the molecular mechanism of energy demand in folliculogenesis and guide the clinical treatment of infertility due to abnormal follicular development.This article reviews recent research advances in the energy demand and regulatory mechanism in different states of folliculogenesis.
Energy Metabolism ; Female ; Glycolysis ; Granulosa Cells ; Humans ; Intercellular Signaling Peptides and Proteins ; Oocytes ; Ovarian Follicle ; growth & development ; Theca Cells

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

Sex cord tumors with annular tubules are known to originate from the sex cord of embryonic gonads that synthesize Sertoli cells, Leydig cells, granulosa cells, and theca cells of the ovarian stroma, while ovarian small cell carcinoma of the hypercalcemic type is a type of neuroendocrine tumor. Both these tumors are uncommon, potentially malignant neoplasms in children. We report the case of a sex cord tumor with annular tubules in an 11-year-old girl and a case of small cell carcinoma of the hypercalcemic type in a 10-year-old girl. We also discuss the prognosis and management of these tumors.
Carcinoma, Small Cell ; Child* ; Female ; Gonads ; Granulosa Cells ; Humans ; Hypercalcemia ; Leydig Cells ; Male ; Neuroendocrine Tumors ; Ovary* ; Prognosis ; Sertoli Cells ; Theca Cells

It has been revealed that multiple cohorts of tertiary follicles develop during some animal estrous cycle and the human menstrual cycle. To reach developmental competence, oocytes need the support of somatic cells. During embryogenesis, the primordial germ cells appear, travel to the gonadal rudiments, and form follicles. The female germ cells develop within the somatic cells of the ovary, granulosa cells, and theca cells. How the oocyte and follicle cells support each other has been seriously studied. The latest technologies in genes and proteins and genetic engineering have allowed us to collect a great deal of information about folliculogenesis. For example, a few web pages (http://www.ncbi.nlm.nih.gov; http://mrg.genetics.washington.edu) provide access to databases of genomes, sequences of transcriptomes, and various tools for analyzing and discovering genes important in ovarian development. Formation of the antrum (tertiary follicle) is the final phase of folliculogenesis and the transition from intraovarian to extraovian regulation. This final step coordinates with the hypothalamic-pituitary-ovarian axis. On the other hand, currently, follicle physiology is under intense investigation, as little is known about how to overcome women's ovarian problems or how to develop competent oocytes from in vitro follicle culture or transplantation. In this review, some of the known roles of hormones and some of the genes involved in tertiary follicle growth and the general characteristics of tertiary follicles are summarized. In addition, in vitro culture of tertiary follicles is also discussed as a study model and an assisted reproductive technology model.
Animals ; Axis, Cervical Vertebra ; Cohort Studies ; Embryonic Development ; Estrous Cycle ; Female ; Genetic Engineering ; Genome ; Germ Cells ; Gonads ; Granulosa Cells ; Hand ; Humans ; Menstrual Cycle ; Mental Competency ; Oocytes ; Ovary ; Pregnancy ; Proteins ; Reproductive Techniques, Assisted ; Theca Cells ; Transcriptome ; Transplants

Ovarian hyperstimulation syndrome (OHSS) is a rare, serious complication of assisted reproductive procedures for fertility treatment. Although most cases of OHSS are mild to moderate in nature, its severe form causes life-threatening complications including respiratory distress, renal failure, liver dysfunction, and thromboembolism because of hemoconcentration. We herein report a rare autopsy case of severe OHSS in a 29-year-old woman who underwent controlled ovulation induction. Three days after the administration of human chorionic gonadotropin, she developed abdominal pain and distension. Two days after, she suddenly developed respiratory arrest, hypotension and semicomatose mentality and died of respiratory failure. At autopsy, multifocal thromboembolism was detected in the internal carotid arteries, internal jugular veins, pulmonary arteries, inferior vena cava, renal arteries, and deep leg veins. And there were cerebral edema, anasarca, pleural effusion, massive pulmonary edema, ascites, and bilateral ovarian enlargement. Microscopically, the bilateral ovaries showed multiple well-developed cyst formations consisting of membrana granulosa and theca interna. To the best of our knowledge, this is the first autopsy report of severe OHSS with multifocal arterial and venous thromboembolism.
Abdominal Pain ; Adult ; Ascites ; Autopsy ; Brain Edema ; Carotid Artery, Internal ; Chorionic Gonadotropin ; Edema ; Female ; Fertility ; Humans ; Hypotension ; Jugular Veins ; Leg ; Liver Diseases ; Ovarian Hyperstimulation Syndrome ; Ovary ; Ovulation Induction ; Pleural Effusion ; Pulmonary Artery ; Pulmonary Edema ; Renal Artery ; Renal Insufficiency ; Respiratory Insufficiency ; Theca Cells ; Thromboembolism ; Veins ; Vena Cava, Inferior ; Venous Thromboembolism

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy causing anovulation in women of childbearing age. It has been well established that estrogen receptor-alpha knockout (ERalphaKO) mice display several pathologic ovarian phenotypes of PCOS. The aims of this study were to determine ovarian pathology in new ERalphaKO mice using a CreloxP approach and intra-ovarian ERalpha function as regulating key aspects of PCOS. METHODS: ERalphaKO mice, which were deficient in exon 3 of the ERalpha gene, were used. Immunohistochemical studies were done on ovaries of control and ERalphaKO mice using antibodies specific to ERalpha, ERbeta, inhibin-alpha, and alpha-smooth muscle actin (SMA), as well as histochemical staining using Sudan black-B. RESULTS: All ovaries of ERalphaKO mice were larger than control mouse ovaries and displayed a disrupted theca-interstitial tissue organization, multiple atretic follicles and multiple hemorrhagic cysts. None of the ERalphaKO mouse ovaries showed a corpus luteum. In addition, heavy deposition of Sudan black-B positive foamy cells was seen. The theca externa of preantral immature follicles and hemorrhagic cysts showed strong expression of alpha-SMA. CONCLUSIONS: ERalphaKO mice show hemorrhagic polycystic ovaries and hyperplasia of the theca externa. This study demonstrates that the ERalpha is the functional key to the pathogenesis of PCOS.
Actins ; Animals ; Anovulation ; Antibodies ; Corpus Luteum ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Estrogens ; Exons ; Female ; Humans ; Hyperplasia ; Immunohistochemistry ; Mice ; Mice, Knockout ; Muscles ; Ovarian Follicle ; Ovary ; Phenotype ; Polycystic Ovary Syndrome ; Sudan ; Theca Cells

Follicular cystic ovary (FCO) is one of the most frequently diagnosed ovarian diseases and is a major cause of reproductive failure in mammalian species. However, the mechanism by which FCO is induced remains unclear. Genetic alterations which affect the functioning of many kinds of cells and/or tissues could be present in cystic ovaries. In this study, we performed a comparison analysis of gene expression in order to identify new molecules useful in discrimination of bovine FCO with follicular cystic follicles (FCFs). Normal follicles and FCFs were classified based on their sizes (5 to 10 mm and > or =25 mm). These follicles had granulosa cell layer and theca interna and the hormone 17beta-estradiol (E2)/ progesterone (P4) ratio in follicles was greater than one. Perifollicular regions including follicles were used for the preparation of RNA or protein. Differentially expressed genes (DEG) that showed greater than a 2-fold change in expression were screened by the annealing control primer (ACP)-based PCR method using GeneFishing(TM) DEG kits in bovine normal follicles and FCFs. We identified two DEGs in the FCFs: ribosomal protein L15 (RPL15) and microtubule-associated protein 1B (MAP1B) based on BLAST searches of the NCBI GenBank. Consistent with the ACP analysis, semi-quantitative PCR data and Western blot analyses revealed an up-regulation of RPL15 and a down-regulation of MAP1B in FCFs. These results suggest that RPL15 and MAP1B may be involved in the regulation of pathological processes in bovine FCOs and may help to establish a bovine gene data-base for the discrimination of FCOs from normal ovaries.
Blotting, Western ; Databases, Nucleic Acid ; Discrimination (Psychology) ; Down-Regulation ; Estrogens ; Female ; Follicular Cyst ; Gene Expression ; Granulosa Cells ; Microtubule-Associated Proteins ; Ovarian Diseases ; Ovary ; Pathologic Processes ; Polymerase Chain Reaction ; Progesterone ; Ribosomal Proteins ; RNA ; Theca Cells ; Up-Regulation

OBJECTIVETo explore the direct contribution of dexamethasone (Dex) for insulin resistance inducing in thecal cells and effects of berberine (Ber) and puerarin (Pue).

METHODSOvarian thecal cells from porcine follicles were isolated and cultured in vitro. Insulin resistance of thecal cells was induced by Dex treatment for 48 h. Then the glucose utilization ratio of thecal cells was detected. Meanwhile, the effects of Ber and Pue on insulin signal transmission and steroid hormones synthesis were determined by RT-PCR and Western blotting.

RESULTS(1) After being treated by Dex for 48 h, the [3-3H] -glucose uptake in cells was lowered by about half, and the glucose content in supernate increased for about 1/3. (2) The RT-PCR and Western blotting showed that levels of insulin receptor substrate-1 (IRS-1), mRNA and protein expression of glucose transporter 4 (GLUT4) lowered, peroxisome proliferator-activated receptor -gamma(PPARgamma) and cytochrome P450 17 hydroxylase (CYP17) mRNA or protein expression increased in the model cells. However, the changes of above insulin signal molecules and CYP17 expression were inversed significantly after treated with Ber and Pue for 48 h. (3) As compared with the control, in the model cells, levels of testosterone (T, microg/mL) was higher (0.82 +/- 0.20 vs 0.38 +/- 0.01, P < 0.05), while after Ber and Pue treatment it was 0.44 +/- 0.24 and 0.45 +/- 0.21 respectively, all lower than that in the model cells (P < 0.05). No significant change of serum progesterone was found in all groups (P > 0.05).

CONCLUSIONSAfter insulin resistance has been induced, the androgen synthetic capacity of thecal cells enhanced significantly. Ber and Pue could lower the degree of insulin resistance and the androgen synthesis in the model cells, displaying the favorable prospect of the two insulin sensitizing agents for the treatment of polycystic syndrome.

Animals ; Berberine ; pharmacology ; Cells, Cultured ; Female ; Insulin Resistance ; Isoflavones ; pharmacology ; Ovary ; cytology ; drug effects ; Swine ; Theca Cells ; drug effects

OBJECTIVES: The purpose of this study is to investigate the expression of CDK (Cyclin dependent kinase) inhibitor, p57(kip2) in human ovarian corpus luteum, benign and malignant ovarian tumors. METHODS: 46 women undergoing laparoscopic surgery or laparotomy for ovarian tumors were enrolled. Total 46 formalin-fixed, paraffin-embedded sections of corpus luteum, benign and malignant ovarian tumors were stained by immunohistochemistry for expression of p57(kip2). RESULTS: p57(kip2) was stained in theca cell of growing follicle but not induced in human corpus luteum. There was the expression of p57(kip2) in mature teratoma, immature teratoma and endometrioma but not in epithelial ovarian tumors. CONCLUSIONS: These results showed that p57(kip2) expression may be not important in luteinization of the ovary and seemed not to play a role in development of epithelial ovarian tumors. However, it may involve pathogenesis of mature teratoma, immature teratoma and endometrioma.
Corpus Luteum ; Endometriosis ; Female ; Humans ; Immunohistochemistry ; Laparoscopy ; Laparotomy ; Lutein ; Luteinization ; Ovary ; Teratoma ; Theca Cells

Polycysytic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by chronic anovulation and hyperandrogenism. The etiology of PCOS is complex and incompletely understood. Accumulating data conclude that hyperinsulinemia and hyperandrogenemia may cause hormonal abnormalities that lead to disturbance of ovarian function. Although insulin resistance is not a part of the diagnostic criteria for PCOS, its importance in its pathogenesis can not be ignored. Excess insulin is capable of stimulating steroidogenesis and therefore excessive androgen production occurs from the theca cell system. Recently, the effects of insulin sensitizer in PCOS patients are being reported and they include the improvement of menstrual pattern, improvement in hyperandrogenism, increased response in ovulation induction and prevention of cardiovascular diseases. Understanding the relation of PCOS and insulin resistance will offer an improvement in treatment of PCOS in the future.
Anovulation ; Cardiovascular Diseases ; Female ; Humans ; Hyperandrogenism ; Hyperinsulinism ; Insulin Resistance* ; Insulin* ; Ovary ; Ovulation Induction ; Polycystic Ovary Syndrome* ; Theca Cells