Pathogenesis Of Ovarian Dysfunction Research Articles

Cellular senescence in the pathogenesis of ovarian dysfunction.

The follicular microenvironment is crucial for normal ovarian function, and intra-ovarian factors, in coordination with gonadotropins, contribute to its regulation. Recent research has revealed that the accumulation of senescent cells worsens the adverse environment of various tissues and plays critical roles in chronological aging and various pathological conditions. Cellular senescence involves cell-cycle arrest, a senescence-associated secretory phenotype (SASP), macromolecular damage, and dysmetabolism. In this review, I summarize the latest knowledge regarding the role of cellular senescence in pathological conditions in the ovary, in the context of reproduction. Specifically, cellular senescence is known to impair follicular and oocyte health in cisplatin- and cyclophosphamide-induced primary ovarian insufficiency and to contribute to the pathogenesis of polycystic ovary syndrome (PCOS). In addition, cellular senescence is induced during the decline in ovarian reserve that is associated with chronological aging, endometriosis, psychological stress, and obesity, but it remains unclear whether it plays a causative role in these conditions. Finally, I discuss the potential for use of cellular senescence as a novel therapeutic target. The modification of SASP using a senomorphic and/or the elimination of senescent cells using a senolytic represent promising therapeutic strategies. Further elucidation of the role of cellular senescence in the effects of various insults on ovarian reserve, including chronological aging, as well as in pathogenesis of ovarian pathologies, including PCOS, may facilitate a new era of reproductive medicine.

Роль факторов ангиогенеза в патогенезе овариальной дисфункции у подростков

Роль факторов ангиогенеза в патогенезе овариальной дисфункции у подростков

066 The role of autoimmunity in the pathogenesis of ovarian dysfunction in adolescent girls

066 The role of autoimmunity in the pathogenesis of ovarian dysfunction in adolescent girls

Effects of Poly (ADP-ribose) Polymerase Inhibition on DNA Integrity and Gene Expression in Ovarian Follicular Cells in Mice with Endotoxemia

Background:A mouse model of LPS-induced inflammation was used to investigate the effect of pharmacological inhibition of nuclear enzyme PARP-1 on oocyte maturation, apoptotic and necrotic death, as well as DNA integrity of follicular cells. Also, the relative expression of cumulus genes (HAS2, COX2, and GREM1) associated with oocyte developmental competence was assessed. Methods:Mice were treated with the PARP-1 inhibitor, 4-HQN, one hour before LPS administration. After 24 h, oocyte in vitro maturation was detected. Granulosa cell DNA damage was determined by the alkaline comet assay. Live, necrotic and apoptotic cells were identified using double vital staining by fluorescent dyes, Hoechst 33342 and propidium iodide. The expression levels of cumulus genes were assessed using reverse transcriptase PCR. Results:The administration of 4-HQN to LPS-treated mice ameliorated oocyte meiotic maturation and exerted a significant cytoprotective effect. 4-HQN attenuated LPS-induced DNA damage and favored cell survival by decreasing necrosis and apoptosis in granulosa cells. Exposure to 4-HQN increased mRNA expression levels for HAS2, COX2, and GREM1 in cumulus cells. Conclusion:The obtained results indicate the involvement of PARP-1 in the pathogenesis of ovarian dysfunction caused by LPS. We suppose that this enzyme can be an attractive target for the therapy of inflammatory disorders in ovary. The protective action of PARP-1 inhibition could at least partly be associated with the reduction of necrotic death of follicular cells and also in other cells. However, the detailed mechanisms of the favorable effect of PARP inhibitors on endotoxin-induced ovarian disorders need to be further explored.

Clinical characteristics of women with infertility and ovaricovaricocele

Despite numerous studies devoted to the etiological factors and pathogenetic aspects of infertility, the lack of a comprehensive analysis of the causes of ovarian dysfunction and the exact diagnosis leads to the polypharmacy of hormonal drugs and their low effectiveness. One of the less well known and poorly studied factors is pelvic venous complications, including varicose veins of the ovaries. Violation of venous circulation in the pelvic organs plays a significant role in the structure of gynecological pathology, particularly in the development of ovarian dysfunction. The purpose of our study was to analyze the clinical characteristics of women with functional infertility and ovaricovaricocele, namely the features of anamnesis of life, gynecological and somatic anamnesis, the study of which allows to assess and determine the risk factors, possible causes of ovarian dysfunction and the formation of varicose veins. To solve the goals and objectives, were prospectively examined and divided into 2 groups for the comparative analysis 117 pregnant women of reproductive age (21–44 years old) with functional infertility: the main group was 62 women with infertility and varicose veins in the ovaries; comparison group has 55 women with infertility without varicose veins. Patients were examined by a specially designed questionnaire, which included the results of gynecological and somatic anamnesis, anamnesis of life. In the main group of women there is an increased proportion of women with intellectual differentiation of labor and psycho-emotional and physical activity, which may be the basis for the formation of maladaptation syndrome with the subsequent occurrence of functional disorders of the reproductive system. In addition, conditions of work with considerable physical activity can indirectly have a negative effect on venous hemodynamics in the small pelvis. Women with functional infertility and ovaricovaricocele had a high incidence of infectious diseases in childhood — 83.9%. It is precisely at the stage of formation of reproductive function that the action of an infectious factor can be significant in the occurrence of violations of complete oogenesis in the subsequent reproductive life of patients. Attention is drawn to the large number of inflammatory diseases of the internal organs in women as the main group and the comparison group in the study of the somatic anamnesis: from the otolaryngologic organs — 48.3%, respiratory organs – 54.7%, genitourinary system — 43.5% and in the structure of gynecological diseases: inflammation of ovaries — 43.5%, vagina and cervix — 25.8%, suggesting that factors of violations of folliculogenesis in active reproductive age may be inflammatory diseases of the genitals. There is a significant percentage of dyshormonal abnormalities in the form of abnormal uterine bleeding in the structure of gynecological pathology in women with functional infertility and ovaricovaricocele (30.6%) against patients with infertility without structural changes in ovarian veins. Patients with infertility are more likely to point out dysgharmony of sexual life (58.1%), which in patients with varicose veins in the pelvic organs was accompanied by dyspareunia (32.2%), suggesting the role of chronic stress as a risk factor for ovarian dysfunction, which is also exacerbated by the presence pain of syndrome in the lower abdomen in women of the main group (77,4%). The more significant percentage of gynecological pathology of endocrine genesis in women with functional infertility and ovaricovaricocele and the presence of certain extragenital pathology, which affects the formation of pelvic pelvic flooring in comparison with patients with infertility without structural changes in ovarian veins, is established during the analysis of the clinical characteristics of the significant percentage of venous hemodynamics in the functional properties of the ovary and induces further investigation of the role of varicose veins of the pelvic reservoirs, in particular ovariсovariсocele, in the pathogenesis of ovarian dysfunction in order to further develop the methods of therapeutic correction.

Pathogenesis of ovarian dysfunction in women with diabetes mellitus 1 type

The main ideas about the pathogenesis of ovarian dysfunction in women with diabetes mellitus (DM) type 1 are presented. The role of increased opioid and dopaminergic tone in the pathogenesis of reducing the synthesis of the gonadotropin-releasing hormone by the hypothalamus in women with type 1 diabetes was analyzed. Presented the data of relationship between ovarian hormonal insufficiency in women with type 1 diabetes with possible damage of positive feedback mechanism of the ovaries and the pituitary gland, which intactness is necessary for the maturation of the dominant follicle and ovulation. The results of studies, suggested that the high doses of exogenously administered insulin in type 1 DM lead to stimulation of androgen synthesis in teca cells and ovarian stroma and the development of ovarian hyperandrogenemia, as well as polycystic ovary syndrome, are reduced. In addition to exogenous hyperinsulinemia, in the pathogenesis of ovarian dysfunction, the value of the deficiency of endogenous insulin, leading to a violation of steroidogenesis in the tissues of the ovary and anovulation, is proved. The role of insulin deficiency and hyperglycemia in the development of metabolic stress lead to ovarian dysfunction in patients with type 1 diabetes was analyzed.

The Polymorphisms of PPARγ Pro12Ala and PGC-1 Gly482Ser in Chinese Women With Polycystic Ovary Syndrome

ObjectivePolycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic diseases and is characterized by ovarian androgen overproduction, polycystic ovary and oligo- or anovulation. Insulin resistance has been implicated in the pathogenesis of ovarian dysfunction in PCOS. Insulin-mediated carbohydrate metabolism and sensitizing effects of thiazolidinedione are regulated at least in part by peroxisome proliferator-activated receptor-γ (PPARγ) and peroxisome proliferator activated receptor γ coactivator-1 (PGC-1).In this study, we defined the role of polymorphisms of PPARγ Pro12Ala and PGC-1 Gly482Ser in Chinese women with Polycystic ovary syndrome.DesignControlled clinical study .Materials and methodsTwo hundred and one PCOS patients and 147 controls were recruited in University-affiliated department. Menarche age was recorded. Body mass indices were calculated. Blood samples were obtained for DNA analyses of PPARγ and PGC-1 polymorphisms,and hormone measurements.ResultsIn Chinese subjects the frequencies of genotypes were as follows: 0.914 Pro12pro, 0.083 Pro12Ala, 0.003 Ala12Ala for the PPARγ2 gene and 0.329 Gly482Gly, 0.392 Gly482Ser, 0.279 Ser482Ser for the PGC-1 gene. The Ala allele frequency (4.4%) is lower, and Ser allele frequency (34.1%) is higher in Chinese subjects, as compared with that of western countries. Both Pro12Ala polymorphism and Gly482Ser polymorphism distributions are similar between Chinese women with PCOS and control. There are no significant differernces of BMI and reproductive hormones such as Total testosterone (T) levels, FSH, LH, P, E2 and PRL levels between the patients and controls.ConclusionOur data suggests there is no association between these polymorphisms and the risk of PCOS in Chinese subjects. ObjectivePolycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic diseases and is characterized by ovarian androgen overproduction, polycystic ovary and oligo- or anovulation. Insulin resistance has been implicated in the pathogenesis of ovarian dysfunction in PCOS. Insulin-mediated carbohydrate metabolism and sensitizing effects of thiazolidinedione are regulated at least in part by peroxisome proliferator-activated receptor-γ (PPARγ) and peroxisome proliferator activated receptor γ coactivator-1 (PGC-1).In this study, we defined the role of polymorphisms of PPARγ Pro12Ala and PGC-1 Gly482Ser in Chinese women with Polycystic ovary syndrome. Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic diseases and is characterized by ovarian androgen overproduction, polycystic ovary and oligo- or anovulation. Insulin resistance has been implicated in the pathogenesis of ovarian dysfunction in PCOS. Insulin-mediated carbohydrate metabolism and sensitizing effects of thiazolidinedione are regulated at least in part by peroxisome proliferator-activated receptor-γ (PPARγ) and peroxisome proliferator activated receptor γ coactivator-1 (PGC-1).In this study, we defined the role of polymorphisms of PPARγ Pro12Ala and PGC-1 Gly482Ser in Chinese women with Polycystic ovary syndrome. DesignControlled clinical study . Controlled clinical study . Materials and methodsTwo hundred and one PCOS patients and 147 controls were recruited in University-affiliated department. Menarche age was recorded. Body mass indices were calculated. Blood samples were obtained for DNA analyses of PPARγ and PGC-1 polymorphisms,and hormone measurements. Two hundred and one PCOS patients and 147 controls were recruited in University-affiliated department. Menarche age was recorded. Body mass indices were calculated. Blood samples were obtained for DNA analyses of PPARγ and PGC-1 polymorphisms,and hormone measurements. ResultsIn Chinese subjects the frequencies of genotypes were as follows: 0.914 Pro12pro, 0.083 Pro12Ala, 0.003 Ala12Ala for the PPARγ2 gene and 0.329 Gly482Gly, 0.392 Gly482Ser, 0.279 Ser482Ser for the PGC-1 gene. The Ala allele frequency (4.4%) is lower, and Ser allele frequency (34.1%) is higher in Chinese subjects, as compared with that of western countries. Both Pro12Ala polymorphism and Gly482Ser polymorphism distributions are similar between Chinese women with PCOS and control. There are no significant differernces of BMI and reproductive hormones such as Total testosterone (T) levels, FSH, LH, P, E2 and PRL levels between the patients and controls. In Chinese subjects the frequencies of genotypes were as follows: 0.914 Pro12pro, 0.083 Pro12Ala, 0.003 Ala12Ala for the PPARγ2 gene and 0.329 Gly482Gly, 0.392 Gly482Ser, 0.279 Ser482Ser for the PGC-1 gene. The Ala allele frequency (4.4%) is lower, and Ser allele frequency (34.1%) is higher in Chinese subjects, as compared with that of western countries. Both Pro12Ala polymorphism and Gly482Ser polymorphism distributions are similar between Chinese women with PCOS and control. There are no significant differernces of BMI and reproductive hormones such as Total testosterone (T) levels, FSH, LH, P, E2 and PRL levels between the patients and controls. ConclusionOur data suggests there is no association between these polymorphisms and the risk of PCOS in Chinese subjects. Our data suggests there is no association between these polymorphisms and the risk of PCOS in Chinese subjects.

Ovarian function in chronic renal failure: evidence suggesting hypothalamic anovulation.

The pathogenesis of ovarian dysfunction in uremia was evaluated in 24 patients by measurements of plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone, prolactin, estradiol, and progesterone basally and after clomiphene, ethinyl estradiol, and bromocriptine. In the 17 premenopausal women, levels of plasma estradiol, progesterone, and FSH were comparable to those found in normal women during the follicular phase of the ovarian cycle; plasma luteinizing hormone was slightly elevated. In most patients, there was an absence of cyclicity. After clomiphene, plasma levels of luteinizing hormone, FSH, and estradiol rose; after ethinyl estradiol, plasma luteinizing hormone levels failed to increase. In seven postmenopausal patients, plasma estradiol was undetectable and gonadotropin levels were markedly elevated. Although plasma prolactin was generally elevated, suppression of prolactin with bromocriptine resulted in resumption of ovulation in only one patient; the other 2 remained amenorrheic. In uremic women, the continued secretion of estrogen, the rise of plasma levels of luteinizing hormone, FSH, and estradiol after clomiphene, and the elevated gonadotropin levels during menopause suggest that the negative estradiol feedback, the tonic gonadotropin secretion, and the pituitary ovarian axis were normal. The positive estradiol feedback associated with cyclic release of luteinizing hormone, however, was impaired as indicated by the prevalence of acyclicity and the failure of luteinizing hormone levels, to rise after ethinyl estradiol.