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PubMed2001

Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus.

The polycystic ovary syndrome (PCOS) is one of the commonest female endocrinopathies affecting 5-10% of women of reproductive age. The disorder, characterized by chronic anovulation and signs of hyperandrogenism, results from a complex interaction between genetic predisposing factors and environmental triggers. We have studied 85 Caucasian PCOS patients and 87 age-matched Caucasian control women for associations with four candidate genes: follistatin, CYP19 (aromatase), CYP17a, and the insulin receptor (INSR). These genes were analyzed using microsatellite markers located near or inside the genes. We found that only the insulin receptor gene marker D19S884 was significantly associated with PCOS (p=0.006 and even after a conservative correction p=0.042). The INSR gene region was then fine mapped with an additional panel of 9 markers but only marker D19S884, located 1 cM telomeric to the INSR gene, was again associated with PCOS. In conclusion, our results suggested that a susceptibility gene for PCOS was located on chromosome 19p13.3 in the insulin receptor gene region. It remains to be determined if this susceptibility gene is the insulin receptor gene itself or a closely located gene. Since insulin stimulates androgen secretion by the ovarian stroma it is likely that INSR function in the ovary is involved in the genetic susceptibility ot PCOS.

Adolescent↗
PubMed2004

Recent advances in the treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder that presents a challenge for clinical investigators. It is the most common endocrine disorder of reproductive-aged women, yet the optimal therapeutic approach is unknown because the pathophysiological and molecular basis of the syndrome is not fully understood. Currently, the treatment is targeted to the patient's primary complaint. Treatment strategies focus on the reduction of clinical manifestations of hyperandrogenism (e.g., hirsutism), restoration of regular menses and achieving pregnancy. Pharmacological agents available for the treatment of hirsutism include androgen suppressors and peripheral androgen blockers. Combined oral contraceptive pills are the most commonly used androgen suppressor and the treatment of choice for menstrual dysfunction in PCOS patients who do not desire pregnancy. The first-line treatment for infertility in PCOS is clomiphene-citrate, whereas parenteral gonadotropins are commonly used in clomiphene-resistant patients. The benefits of insulin-sensitising agents for PCOS patients have become increasingly clear over the last decade. Metabolic disturbances associated with PCOS appear to have important long-term health implications and require further attention. This review summarises the current and emerging therapeutic strategies for the management of PCOS.

Disease Management↗
PubMed2005

Adipokines: implications for female fertility and obesity.

Obesity is associated with a diverse set of metabolic disorders, and has reproductive consequences that are complex and not well understood. The adipose tissue-produced leptin has dominated the literature with regards to female fertility complications, but it is pertinent to explore the likely role of other adipokines--adiponectin and resistin--as our understanding of their biological functions emerge. Leptin influences the developing embryo, the functioning of the ovary and the endometrium, interacts with the release and activity of gonadotrophins and the hormones that control their synthesis. In this review such biological actions and potential roles of the adipokines leptin, adiponectin and resistin are explored in relation to female fertility and the complexity of the obese metabolic state.

Adiponectin↗
PubMed2000

Special considerations for women with epilepsy.

Women with epilepsy present health care providers with unique problems and opportunities for advancement of care. The fundamentals of epileptic pathophysiology are similar in both sexes. There are, however, some significant differences. Cosmetic effects of antiepileptic drugs (AEDs) may have different implications for women. Women who have seizures associated with their menstrual cycle may need special attention regarding their cyclic hormonal changes and AED selection. Antiepileptic drugs may reduce the effectiveness of hormonal contraception. Women with epilepsy have higher rates of infertility and an increased prevalence of reproductive and endocrine disorders. The majority of women with epilepsy have normal, healthy children, but their pregnancies are considered high risk due to an increase in seizure frequency, metabolic alterations of AEDs (which complicate management), and an increased risk of adverse pregnancy outcomes. These issues and an approach to optimize the management of women with epilepsy are discussed.

Adult↗
PubMed1984

Sexual inhibition in a prosimian primate: a pheromone-like effect.

The effect of dominant urine odour on plasma levels of testosterone and cortisol was studied in the prosimian primate Microcebus murinus. This species shows a photoperiod-dependent cycle of sexual activity. In particular, mean testosterone levels vary from 15 nmol/l during the annual rest period to 245 nmol/l during the breeding season. When males of this solitary and territorial species are artificially grouped in captivity, they develop a social hierarchy which in turn results in physiological disorders, especially of reproductive function, in non-dominant individuals. Since olfactory behaviours appear to be important in the establishment and maintenance of the social structure, we have tested the effects of dominant odorant signals upon the sexual inhibition observed in male conspecifics. A preliminary experiment showed that a decrease in plasma testosterone concentrations could be induced by dominant scent marks. Furthermore, dominant urine odour alone was found to be sufficient to induce this modification. Plasma cortisol levels also increased in these animals. Conversely, when sexually inhibited males were olfactorily isolated from dominant urine odour, testosterone and cortisol concentrations returned to a normal seasonal level. These effects were observed even in males which had had no previous contact with the dominant urine donor. It is inferred from these results that a pheromone-like process could lead to sexual inhibition in male Microcebus murinus exposed to an odorant urinary signal produced by a dominant individual. Nevertheless, the endocrine response seems to vary according to the seasonal period of the sexual activity cycle which suggests that the social effect described is modulated by other external (e.g. photoperiodic) or internal (e.g. reproductive physiology) factors.

Animals↗
PubMed1989

Reverse hemolytic plaque assay study of luteinizing and follicle-stimulating hormone and thyrotropin secretion in diabetic rat pituitary glands.

Numerous studies indicate that an impaired hypothalamopituitary axis plays an important role in reproductive and thyroid disorders in diabetic humans and animal models. Yet, several questions about the pathogenesis of these diabetic complications have not been answered. To evaluate the basal secretion of single gonadotrophs and thyrotrophs in vitro, uncultured pituitary cells from control rats and 1-mo streptozocin-induced diabetic (STZ-D) rats were studied with a reverse hemolytic plaque assay and morphometry. After light-microscopy immunocytochemistry for gonadotropin and thyrotropin (TSH), we recorded the ratio of plaque-forming to non-plaque-forming cells. The area of plaques produced by luteinizing hormone (LH), follicle-stimulating hormone (FSH), and TSH cells and the area of plaque-forming and non-plaque-forming cells were clearly smaller in diabetic than control rats. The plaque area, however, was more severely reduced than the cell area. The percentage of LH-, FSH-, and TSH-immunoreactive plaque-forming cells was greatly decreased in diabetic compared with control animals. In conclusion, our findings demonstrate that the LH-, FSH-, and TSH-secreting cells of diabetic rats released less hormone and were less numerous than the corresponding cells of control rats. Thus, several pathogenetic mechanisms might be involved in reduced gonadotropin and TSH release at the cellular level: 1) anatomical lesions of organelles involved in glycoprotein hormone synthesis and secretion, possibly due to insulin deficiency; 2) decreased gonadotropin-releasing hormone (GnRH) and thyrotropin-releasing hormone (TRH) receptors on pituitary cells; 3) inadequate GnRH and TRH stimulation; 4) high plasma corticosterone levels; or 5) a combination of points 1-4.

Animals↗
PubMed1976

Mortality and production characteristics of laying chickens fed high- and low-erucic acid rapeseed oils.

Laying pullets were fed a diet supplemented with three percent of either high-erucic acid rapeseed (HEAR) oil or low-erucic acid rapeseed (LEAR) oil for 39 weeks. Egg production for the period was 78.8 and 80.1% by the birds fed the respective oils. Average egg weights were 56.8 and 58.7 g. respectively. Gains in body weight, liver weight and adrenal gland weight were similar with the two types of oil fed. Feed consumption was similar for the two groups of birds. The efficiency of utilization of the diet containing HEAR oil was accordingly lower than that of the diet containing LEAR oil. In the birds fed HEAR and LEAR oil respectively mortality attributed to metabolic disorders of the reproductive system, liver, and kidney was 3.3% and 1.2%. Mortality from other causes in the birds fed the two oils was 3.2 and 3.8% of the original populations.

Animals↗
PubMed2025

CRISPR as a Tool to Uncover Gene Function in Polycystic Ovary Syndrome: A Literature Review of Experimental Models Targeting Ovarian and Metabolic Genes.

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities such as hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently accompanied by metabolic disturbances such as insulin resistance, obesity and dyslipidemia. Genome-wide association studies (GWASs) have identified several susceptibility loci, yet little is known about their functional implications. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a powerful gene editing tool in bridging this gap by allowing researchers to directly target candidate genes in ovarian and metabolic pathways. For instance, experimental models have highlighted the role of CYP17A1 and DENND1A.V2 in androgen excess, anti-Müllerian hormone (AMH) in follicular arrest, and insulin receptor substrate 1 (IRS1) and PPARγ in insulin signaling and adipogenesis. To highlight the multifactorial nature of PCOS, animal models, including zebrafish and rodents, have been used to reveal interactions between reproductive and metabolic phenotypes. Nevertheless, most studies remain restricted to single-gene models, and dual-gene models or combined gene editing and hormonal induction models remain underexplored. Future research integrating precision editing, multi-omic platforms, and patient-derived organoids may provide more accurate disease models and novel therapeutic strategies.

Polycystic Ovary Syndrome↗
PubMed1983

Antiarrhythmic drug therapy during pregnancy.

Pregnancy increases the work demands on the heart by increasing blood volume and thereby cardiac output. Therefore, in pregnant patients with organic heart disease, arrhythmias may have significant hemodynamic consequences to the mother with harm to the fetus. As a result of improved medical therapy, an increasing number of women with cardiac diseases or rhythm disorders reach their reproductive years and require medication. Information on the effect of antiarrhythmic agents on the human fetus as well as the possible changes in therapeutic response during the altered state of pregnancy is limited. In principle, the approach to the treatment of arrhythmias in pregnant patients is similar to that in nonpregnant patients. Special consideration, however, must be given with regard to drug selection and dosage in order to avoid adverse effects on the mother and fetus.

Adrenergic beta-Antagonists↗
PubMed2001

Prevalence of antibodies to Encephalitozoon cuniculi (microsporidia) in angora goats--a potential risk of infection for breeders.

The presence of antibodies against Encephalitozoon cuniculi in Angora goats was detected by the method of indirect immunofluorescence (IFAT). The animals reacting at the titre 1: 64 and more were considered positive. Of the total number of 48 sera examined, 4 were positive at the titre 1: 32 and 2 were positive at the titre 1: 64. The occurrence of antibodies against E. cuniculi indicates that one of the causes of disorders in the reproductive cycle in Angora goats may be microsporidia Encephalitozoon cuniculi, and that these animals may be potential sources of infection for people.

Animals↗
PubMed2002

Gender differences in depression.

Depression is twice as common in women as in men, although some concern has been raised in terms of misdiagnosing depression in men. The incidence of depression in women varies during the life span. The peak incidence during childbearing years appears to be associated with cyclic hormonal changes. Women also present with reproductive -specific mood disorders: pre-menstrual dysphoric disorder (PMDD), depression in pregnancy, postpartal mood disorder (PDD) and perimenopausal depressive disorder. Gender differences were repeatedly observed in response to antidepressant medication. Premenopausal women appear to respond poorly and to show low tolerability to TCAs, but they tend to show greater responsiveness to the SSRIs. In contrast, men and postmenopausal women can respond equally to the TCAs and SSRIs. These differences are contributed to gender differences in pharmacokinetics of antidepressants and to the influence of menstrual cycle. These findings suggest the need for a gender-specific approach to the evaluation and management of depression.

Antidepressive Agents↗
PubMed2002

[Chemical substances in the Russian urban environment: hazard to human health and prospects for its prevention].

The paper deals with the situation associated with some substances, as described by the UNEP/Chemicals as priority persistent toxic, in the Russian Federation. Among them, lead was shown to head the list of them and its blood levels may be greater than the recommended allowable level of 10 micrograms/dl in almost 2 million children in different regions of the country. Exposure to mercury and cadmium is of local character, but some regions (the Irkutsk Region, Bashkiria, Vladikavkaz, V. Pyshma) showed specific changes in human health. Among persistent organic pollutants (POPs) there are polychlorinated biphenyls (PCBs) extensively used in the transformers, which present the greatest hazard. These substances were found to be of significance as a risk factor (OR = 1.7, 95% CI 0.9-1.3) for female infertility in the town of Serpukhov where PCB-containing capacitors were manufactured. Reproductive and endocrine disorders (higher incidence of abortions, infertility, late gestoses, cryptorchidism, retarded male sexual development, etc.) are common in the residents of Chapaevsk (Samara Region), one of the world's most dioxin-contaminated towns. In the female residents of this town, the highest global concentrations of dioxins were recorded in the breast milk and blood (43.3 and 24-75 pg TEQ/g fat, respectively). The ambient air in the most industrial towns of Russia was demonstrated to contain increased benz(a)pyrene, but there is very little analytical environmental and epidemiological evidence for the carcinogenic effect of these substances by taking into account of the factor of smoking. The population of many cities and towns in Russia is at risk for consumption of drinking water containing excess water disinfection products. Special preventive programs to reduce the adverse effects of the above persistent toxic agents should be elaborated and introduced.

Environmental Pollution↗
PubMed2002

Functional activation of peroxisome proliferator-activated receptor alpha (PPARalpha) by environmental chemicals in relation to their toxicities.

Peroxisome proliferator-activated receptor alpha (PPARalpha) may work in the processes of both physiological and toxicological response to various endogenous or exogenous substances. The literature on the study of functional activation of PPARalpha by environmental chemicals in relation to their toxicities were reviewed. Environmental chemicals that were found to induce peroxisomes (peroxisome proliferators) and to activate the function of PPARalpha included plasticizers, herbicides, and organic solvents that have carboxyl groups in their parent substances or their metabolites. Several studies have showed species differences in the constitutive expression of PPARalpha and activation of PPARalpha, which may result in species differences in the induction of transcription of the genes encoding several peroxisomal enzymes. Although much information has supported the view that PPARalpha is primarily involved in the hepatic carcinogenicity of peroxisome proliferators, conflicting evidence exists. Most of the peroxisome proliferators have been shown to induce reproductive and developmental disorders, which might, in part. be associated with the functional activation of PPARalpha. Few epidemiological studies on the effect of peroxisome proliferators on humans have been conducted. The effect of perfluorooctanoic acid on humans was evaluated from the aspect of lipid metabolism in one study, which concluded that there was no effect.

Animals↗
PubMed2003

Dynamic testing in the evaluation of male gonadal function.

The maturation and physiologic functions of male sexual apparatus are under the control of the hypothalamic-pituitary-gonadal (HPG) axis. The determination of gonadotropins and testosterone as secretory products of pituitary and gonads, respectively, represents the first step in the evaluation of male sexual function and the diagnosis of disorders in male reproductive axis. However, there are several clinical situations that require a dynamic evaluation of this system and the measurement of basal gonadotropins and testosterone must be combined with specific dynamic tests. These mainly consist in GnRH stimulation, which evaluates the endocrine reserve capacity of the pituitary, and human chorionic gonadotropin (hCG) stimulation, which is used in the assessment of Leydig cells activity. The paper illustrates the technical aspects, the normal/pathological responses and the role of these two tests in assessing the male HPG axis in respect to different clinical diagnostic queries.

Adolescent↗
PubMed2005

Polycystic ovary syndrome--a management update.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women and is associated with both reproductive and metabolic disorders. OBJECTIVE: This article discusses the health risks, clinical assessment and investigations consistent with the new internationally agreed definition of PCOS, available treatments, and the long-term monitoring of women with PCOS. DISCUSSION: Women with PCOS have an increased risk of endometrial carcinoma, type 2 diabetes mellitus, and possibly cardiovascular disease. Polycystic ovary syndrome is a diagnosis of exclusion of other causes of hyperandrogenism. Screening for diabetes is important. Treatment is directed at the presenting symptom as the primary cause is unknown. Long-term medical treatment may include the oral contraceptive pill or metformin. Long-term surveillance is recommended for the early detection and treatment of potential metabolic complications.

Contraceptives, Oral↗
PubMedDate not supplied

[Study of dopamine effect on neuroendocrine disorders during polycystic-ovary syndrome using the method of enzyme-linked immunosorbent analysis (ELISA)].

The goal of this work was to study the influence of chronic stress on the development of neuroendocrine disorders and to establish the role of hypothalamo-dopaminergic system in the formation of polycystic-ovary syndrome (POS) of central form. Our data indicate that an increase of luteinizing hormone (LH) in the blood of patients diagnosed with POS of central genesis is conditioned both by the decrease of the influence of dopaminergic system and increased secretory activity of LH releasing generating neutrons causing chronic stress. Thus the fact that well-pronounced decrease of dopamine level is observed in persons forcedly displaced evidences that chronic stress is an important risk factor of the development of POS of central genesis. Chronic stress leads to the disorder of the central mechanisms of neuroregulation of hypothalamo-hypophysial system and aggravation of the disorders of females' reproductive function.

Adult↗
PubMed2004

Development of solid - based paper strips for rapid diagnosis of Pseudorabies infection.

Pseudorabies (Aujeszky's disease) is an economically significant disease of swine known to cause central nervous disorders, respiratory disease, reproductive failure and mortality in infected pigs. In attempts to eradicate the disease from becoming endemic, early detection is important to prevent further economic losses and to allow for detection and removal of infected pigs in domestic herds. Thus, a rapid and sensitive technique is necessary for the detection of the virus. For rapid and simple examination, an immuno - chromatographic lateral - flow assay system based on immunologic recognition of specific pseudorabies virus antigen was developed by utilising, as signal generator, colloidal gold conjugated to secondary antibody to detect primary or sample antibody in the sera of pseudorabies infected animals. The pseudorabies virus used as a capture antigen in the test strip was first cultivated in VERO cell culture and then purified by sucrose gradient separation to produce the viral protein concentration of 3.8 mg/ml. The standard pseudorabies antigens reacted well with the hyperimmune serum (HIS). The antibody detection system is basically composed of colloidal gold - labelled antibodies fixed on a conjugate pad, and the complementary pseudorabies antigen immobilised onto a nitrocellulose membrane forming capture zone. If the target antibody is present in a specimen, the colloidal gold-labelled antibody will form a complex with the antibody sample. Subsequently, the formed complex will migrate to the capture zone and is then bound to the solid phase via antigen - antibody interaction. As a result, a signal marker is generated by the accumulation of colloidal gold for detection confirmation. The results obtained demonstrated that the optimum combination of pseudorabies antigen needed as the capture reagent and gold conjugate as secondary antibody recognition marker was at a concentration of 0.38mg/ml and at 1:10 dilution factor respectively. The sensitivity of the solid - based test strip towards pseudorabies antibodies was high with a detection limit of 1 to 10,000 - dilution factor. The specificity of the assay was 100% with no cross - reaction being observed with other sera or antibodies. Accurate reading time needed for confirmation of the assay can be completed in 5 min with a whole blood sample of 25 microl. The colloidal gold - labelled antibody is stable at room temperature for 6 months or more (data not shown). Findings from this study indicated that the solid - based test strip assay system provided high sensitivity and specificity for the detection of pseudorabies at low levels of antibody concentration. The assay was rapid, simple, cheap, and does not require any sophisticated equipment. Thus, the solid based test strip will be a useful serological screening technique or for rapid diagnosis of an infectious disease in target populations of animals characterised by heterogeneous antibody responses.

Journal Article↗