RESUMEN

In animal models, exposure to excess testosterone during gestation induces polycystic ovary syndrome (PCOS)-like reproductive and metabolic traits in female offspring, suggesting that the hyperandrogenemic intrauterine environment may have a role in the etiology of PCOS. Additionally, few studies have also addressed metabolic and reproductive outcomes in male offspring. In the present study, the intravenous glucose tolerance test (IGTT) was used to assess the insulin-glucose homeostasis at various ages during sexual development in male sheep born to testosterone-treated ewes. To further analyze the programming effect of testosterone on insulin-glucose homeostasis, indexes of insulin sensitivity were assessed in orchidectomized post-pubertal males born to testosterone-treated ewes (Torq-males) and orchidectomized post-puberal controls (Corq-males) before and 48 h after a testosterone injection. There was no difference in insulin sensitivity indexes between males born to testosterone-treated ewes (T-males) and control males born to control ewes (C-males) at 5, 10, 20 and 30 weeks of age, representing the infantile, early and late pre-pubertal, and early post-pubertal stage of sexual development, respectively. In orchidectomized males, basal levels of insulin and glucose were not different between both groups before and after the testosterone injection; however, Torq-males released more insulin before and after T challenge during the first 20 min of the test. Despite this, plasma glucose concentrations were not different in both groups during IVGTT, resulting in an insulin sensitivity index composite similar between groups. We concluded that the effect of prenatal exposure to excess testosterone may reprogram the pancreatic ß-cells insulin release in ovine males, with effects more evident in castrated males versus intact males.

Asunto(s)

Desarrollo Fetal , Resistencia a la Insulina , Exposición Materna , Efectos Tardíos de la Exposición Prenatal , Testosterona , Animales , Femenino , Masculino , Orquiectomía , Embarazo , Maduración Sexual , Ovinos

RESUMEN

Clinical and experimental evidences indicate that epigenetic modifications induced by the prenatal environment are related to metabolic and reproductive derangements in polycystic ovary syndrome (PCOS). Alterations in the leptin and adiponectin systems, androgen signalling and antimüllerian hormone (AMH) levels have been observed in PCOS women and in their offspring. Using a targeted Next-Generation Sequencing (NGS), we studied DNA methylation in promoter regions of the leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), adiponectin receptor 1 and 2 (ADIPOR1 and ADIPOR2), AMH and androgen receptor (AR) genes in 24 sons and daughters of women with PCOS (12 treated with metformin during pregnancy) and 24 children born to non-PCOS women during early infancy (2-3 months of age). Genomic DNA was extracted from whole blood, bisulphite converted and sequenced by NGS. Girls showed differences between groups in 1 CpG site of LEPR, 2 of LEP, 1 of ADIPOR2 and 2 of AR. Boys showed differences in 5 CpG sites of LEP, 3 of AMH and 9 of AR. Maternal metformin treatment prevented some of these changes in LEP, ADIPOR2 and partially in AR in girls, and in LEP and AMH in boys. Maternal BMI at early pregnancy was inversely correlated with the methylation levels of the ChrX-67544981 site in the whole group of girls (r = -0.530, p = 0.008) and with the global Z-score in all boys (r = -0.539, p = 0.007). These data indicate that the intrauterine PCOS environment predisposes the offspring to acquire certain sex-dependent DNA methylation patterns in the promoter regions of metabolic and reproductive genes.

Asunto(s)

Metilación de ADN , Epigénesis Genética , Síndrome del Ovario Poliquístico/genética , Efectos Tardíos de la Exposición Prenatal/genética , Adiponectina/genética , Adiponectina/metabolismo , Adulto , Femenino , Humanos , Lactante , Leptina/genética , Leptina/metabolismo , Masculino , Embarazo , Regiones Promotoras Genéticas , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de Leptina/genética , Receptores de Leptina/metabolismo

RESUMEN

Hyperandrogenemia and metabolic disturbances during postnatal life are strongly linked both to polycystic ovary syndrome and other conditions that arise from prenatal exposure to androgen excess. In an animal model of this condition, we reported that insulin sensitivity (IS) was lower in young female sheep born to testosterone-treated mothers versus sheep born to non-exposed mothers (control). This lower insulin sensitivity remains throughout reproductive life. However, it is unknown whether abnormal postnatal levels of testosterone (T) further decrease IS derived from prenatal exposure to testosterone. Therefore, we assessed the effects of an acute testosterone administration (40 mg) on IS and insulin secretion during an intravenous glucose tolerance test performed at 40 weeks of age (adulthood) in previously ovariectomized sheep at 26 weeks of age (prepuberty), that were either prenatally exposed to testosterone (T-females, n = 6) or not (C-females, n = 6). The incremental area under the curve of insulin was greater in C-females both with or without the acute testosterone treatment (P < 0.05). The ISI-Composite was lower after an acute testosterone treatment, only in T-females. We conclude that prenatal exposure to testosterone disrupts pancreatic insulin secretion in response to glucose and that in this setting further hyperandrogenemia may predispose to lower insulin sensitivity.

Asunto(s)

Desarrollo Embrionario/efectos de los fármacos , Resistencia a la Insulina , Secreción de Insulina/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/patología , Testosterona/efectos adversos , Animales , Femenino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ovinos

RESUMEN

The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

Asunto(s)

Glucemia/metabolismo , Insulina/sangre , Síndrome del Ovario Poliquístico/patología , Efectos Tardíos de la Exposición Prenatal/sangre , Testosterona/farmacología , Animales , Animales Recién Nacidos , Glucemia/análisis , Glucemia/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Desarrollo Fetal/efectos de los fármacos , Feto/efectos de los fármacos , Feto/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/veterinaria , Ovinos , Factores de Tiempo

RESUMEN

Pregnancy complications and obstetric outcomes were compared in 80 Chilean (PPCOSCh) and 70 Argentinian (PPCOSAr) pregnant women. Reference groups of Chilean and Argentinian normal pregnant women from the same antenatal care units were also compared. PPCOSCh showed a higher prevalence of gestational diabetes mellitus (GDM) (OR, 2.28, 95% CI: 1.08-4.77, p = .030) and a lower prevalence of pregnancy-induced hypertension (PIH) (OR, 0.20, 95% CI: 0.07-0.54, p = .001) compared to PPCOSAr. In the normal pregnant groups, the prevalence of PIH was lower in Chilean women compared to Argentinian women (OR, 0.24, 95% CI: 0.10-0.62, p = .001). Similar to the pattern observed in the normal populations, newborns from PPCOSCh had higher birth weight and length compared with the newborns of PPCOSAr (p = .006 and .014, respectively). In conclusion, differences in pregnancy complications and obstetric outcomes between Chilean and Argentinian pregnant women with PCOS could be determined by ethnic diversity together with environmental factors of both populations. Impact Statement What is already known on this subject: The reproductive and metabolic phenotypes of women with polycystic ovary syndrome vary between different populations, which could significantly influence the obstetric and neonatal outcomes in this syndrome. What the results of this study add: Pregnant women with PCOS from two Latin American countries (Chile and Argentina) exhibit differences in the prevalence of gestational diabetes and pregnancy-induced hypertension, and in the birth weight of their newborns. What the implications are of these findings for clinical practice and/or further research: Ethnic diversity together with environmental factors are fundamental elements that must be considered in the management of pregnant women with PCOS.

Asunto(s)

Diabetes Gestacional/epidemiología , Hipertensión Inducida en el Embarazo/epidemiología , Síndrome del Ovario Poliquístico/complicaciones , Adolescente , Adulto , Argentina/epidemiología , Peso al Nacer , Chile/epidemiología , Diabetes Gestacional/etiología , Femenino , Humanos , Hipertensión Inducida en el Embarazo/etiología , Recién Nacido , Embarazo , Resultado del Embarazo , Prevalencia , Factores de Riesgo , Adulto Joven

RESUMEN

CONTEXT: Intrauterine life may be implicated in the origin of polycystic ovary syndrome (PCOS) modifying the endocrine and metabolic functions of children born to PCOS mothers independently of the genetic inheritance and gender. The aim of the present study was to evaluate the reproductive and metabolic functions in sons of women with PCOS during puberty. METHODS: Sixty-nine PCOS sons (PCOSs) and 84 control sons of 7-18 years old matched by the Tanner stage score were studied. A complete physical examination was conducted including anthropometric measurements (weight, height, waist, hip and body mass index). An oral glucose tolerance test was performed and circulating concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), sex hormone-binding globulin, testosterone, androstenedione (A4), 17α-hydroxyprogesterone (17-OHP) and AMH were determined in the fasting sample. RESULTS: Waist-to-hip ratio, FSH and androstenedione levels were significantly higher in the PCOSs group compared to control boys during the Tanner stage II-III. In Tanner stages II-III and IV-V, PCOSs showed significantly higher total cholesterol and LDL levels. Propensity score analysis showed that higher LDL levels were attributable to the PCOSs condition and not to other metabolic factors. AMH levels were comparable during all stages. The rest of the parameters were comparable between both groups. CONCLUSIONS: Sons of women with PCOS show increased total cholesterol and LDL levels during puberty, which may represent latent insulin resistance. Thus, this is a group that should be followed and studied looking for further features of insulin resistance and cardiovascular risk markers. Reproductive markers, on the other hand, are very similar to controls.

RESUMEN

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine metabolic disorder and is presently considered a family pathology. It is associated with obesity, insulin resistance and metabolic syndrome. Racial, ethnic and environmental factors may be important in determining the clinical manifestations of this syndrome. Polycystic ovary syndrome is an exclusion diagnosis and, therefore, should be distinguished from the physiological changes typical for the age and from other hyperandrogenic disorders. Early diagnosis is important since this syndrome is associated with reproductive, oncologic and metabolic risks. Interestingly, the clinical features of this disorder may change throughout the lifespan of a PCOS woman, starting from adolescence to postmenopausal age. During the first decades of life the main features are in the reproductive area, while later in life metabolic abnormalities are more evident. While the assessment of insulin resistance is not part of the diagnosis of PCOS, it has been demonstrated that this metabolic component appears early in life and persists over time. Moreover during puberty and pregnancy, insulin resistance is exacerbated. Pregnancy represents an important stage, as the offspring of these patients may be reprogrammed and inherit some of the metabolic and reproductive features of their mothers. In the present review, we will focus on several metabolic aspects of the PCOS condition at different stages of life in a Chilean population.

Asunto(s)

Esperanza de Vida , Síndrome del Ovario Poliquístico/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Síndrome Metabólico/metabolismo , Obesidad/metabolismo

RESUMEN

OBJECTIVE: To assess insulin sensitivity, insulin secretion and metabolic profile in women with polycystic ovary syndrome (PCOS) in different stages of reproductive life. MATERIALS AND METHODS: In a cross-sectional study, 190 PCOS women (PCOSw) and 99 controls (Cw) aged between 18 and 55years were included. PCOSw and Cw were distributed into 3 stages of reproductive life: early reproductive age (18-34years old), late reproductive age (35-40years old) and perimenopausal period (41-55years old). Waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. An oral glucose tolerance test (OGTT) with measurement of glucose and insulin was performed. Sex steroids and lipid profile were also determined in the fasting sample. Insulin sensitivity was assessed by HOMA-IR and ISI composite, and insulin secretion by HOMA-ß and insulinogenic index. Visceral adiposity index (VAI) and lipid accumulation product (LAP) were also calculated. Metabolic syndrome (MS) was assessed by the IDF and ATPIII criteria. RESULTS: At early reproductive age, PCOSw showed higher BMI, WC, and VAI and a higher prevalence of MS compared to Cw (p<0.05). In addition, at late reproductive age PCOSw also showed elevated total cholesterol, triglycerides, insulin secretion, LAP and BP. At perimenopausal period, these parameters were not different between Cw and PCOSw. Within the PCOSw group, HOMA-ß was lower at late reproductive and perimenopausal periods compared to the early reproductive age. Regarding control women, a deterioration of anthropometric and metabolic parameters was observed in perimenopausal women compared to early and late reproductive women. CONCLUSIONS: Our results suggest that metabolic derangements associated with PCOS are more evident at the early and late reproductive ages. On the other hand, during perimenopause, there is no further deterioration of metabolic parameters. Nevertheless, a disruption in pancreatic ß-cell function is evidenced at this stage.

Asunto(s)

Envejecimiento , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Síndrome Metabólico/etiología , Síndrome del Ovario Poliquístico/fisiopatología , Adiposidad , Adolescente , Adulto , Presión Sanguínea , Índice de Masa Corporal , Chile/epidemiología , Estudios de Cohortes , Estudios Transversales , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Insulina/sangre , Secreción de Insulina , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Prevalencia , Riesgo , Circunferencia de la Cintura , Adulto Joven

RESUMEN

We evaluated the association of hirsutism and oligomenorrhea (persistent menstrual cycles > 45 days) as screening criteria for the detection of biochemical hyperandrogenism (BH) and polycystic ovaries (PCOM) during adolescence and determined which androgens, granulosa cell hormone, ultrasonographic parameters have the best association with polycystic ovary syndrome (PCOS). Hirsute girls with oligomenorrhea (N = 26 Hirs/Oligo group) and non-hirsute girls with regular cycles (N = 63, C group) were studied. Prevalence of BH and PCOM, diagnostic performance of androgens and ultrasound parameters for PCOS diagnosis were analyzed. BH and PCOM prevalence were higher in the Hirs/Oligo girls than in the C girls (76.9% versus 25.5%; 92.3% versus 33.3%, respectively; p < 0.0001). A complete PCOS phenotype (Hirs/Oligo with BH and PCOM) was observed in 73.1% of the Hirs/Oligo group. The presence of both BH and PCOM was observed in 7.9% of the C group. The parameters with the best diagnostic performance were free androgen index ≥6.1, testosterone ≥2.4 nmol/L, follicle number ≥12 and ovarian volume ≥10 ml anti-Müllerian hormone (AMH) exhibited a low diagnostic accuracy. Hirsutism and persistent menstrual cycle over 45 days are highly associated with BH and PCOM suggesting that the presences of both criteria are necessary for the diagnosis of PCOS during adolescence.

Asunto(s)

Hirsutismo/etiología , Oligomenorrea/etiología , Síndrome del Ovario Poliquístico/diagnóstico , Adolescente , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Adulto Joven

RESUMEN

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life. AIM: To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions. MATERIAL AND METHODS: We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype expression was analyzed. RESULTS: Twenty four percent of women became pregnant, 37% decreased and 24% increased their body weight during follow up. These conditions modified significantly the proportion of the different phenotypes (c2 = 32.2, p < 0.001). For instance, weight reduction was associated with a change to a better phenotype (p = 0.047) and even a normalization of the PCOS condition in 27% of the patients. On the other hand, an increase in body weight modifying body mass index in one unit, conferred an 8% probability of changing to a worst phenotype. CONCLUSIONS: Pregnancy and changes in body weight significantly modify PCOS phenotypes.

Asunto(s)

Factores de Edad , Peso Corporal/fisiología , Síndrome del Ovario Poliquístico/fisiopatología , Adolescente , Adulto , Femenino , Humanos , Fenotipo , Embarazo , Estudios Prospectivos , Adulto Joven

RESUMEN

Background: Polycystic Ovary Syndrome (PCOS) is tightly associated with insulin resistance and obesity and characterized by hyperandrogenism, chronic oligo-anovulation and polycystic ovarian morphology when fully expressed. The 2003 Rotterdam consensus proposed that two or three of these features were necessary to make the diagnosis, which generated four phenotypes. Several studies have suggested that these phenotypes could differ in their metabolic and endocrine characteristics and that they could vary in the same patient when analyzed throughout life. Aim: To determine if the initial classification of PCOS phenotypes is modified by different physiological conditions. Material and Methods: We performed a non-concurrent prospective analysis of 88 women with PCOS according to the Rotterdam criteria. The effect of physiological conditions such as changes in body weight, pregnancy and ageing more than five years on PCOS phenotype expression was analyzed. Results: Twenty four percent of women became pregnant, 37% decreased and 24% increased their body weight during follow up. These conditions modified significantly the proportion of the different phenotypes (c2 = 32.2, p < 0.001). For instance, weight reduction was associated with a change to a better phenotype (p = 0.047) and even a normalization of the PCOS condition in 27% of the patients. On the other hand, an increase in body weight modifying body mass index in one unit, conferred an 8% probability of changing to a worst phenotype. Conclusions: Pregnancy and changes in body weight significantly modify PCOS phenotypes.

Asunto(s)

Adolescente , Adulto , Femenino , Humanos , Embarazo , Adulto Joven , Factores de Edad , Peso Corporal/fisiología , Síndrome del Ovario Poliquístico/fisiopatología , Fenotipo , Estudios Prospectivos

RESUMEN

OBJECTIVE: To evaluate the metabolic profile of Chilean and Argentinian women with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria. DESIGN: Observational cross-sectional study. SETTING: Academic centers. PATIENT(S): Women with PCOS, aged 18-39 years: 220 Chilean (PCOSCh) and 206 Argentinian (PCOSAr). INTERVENTION(S): Physical examination, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. MAIN OUTCOME MEASURE(S): Comparative analysis of the metabolic profile in both populations divided into four phenotypes. RESULT(S): The distribution of the different phenotypes was different in both populations. PCOSCh women showed a higher body mass index and a higher percentage of metabolic syndrome in all phenotypes compared with the PCOSAr women. The PCOSAr women exhibited a statistically significantly higher diastolic blood pressure in phenotypes A, B, and C and a higher percentage of hypertension in phenotypes A and D compared with the PCOSCh women. CONCLUSION(S): The data show differences in the metabolic profile of both populations. PCOSCh women presented with greater metabolic alterations such as dysglycemia and dyslipidemia and a higher prevalence of metabolic syndrome, independent of the phenotype. The PCOSAr patients showed more elevated blood pressure. Ethnic diversity associated with environmental factors are fundamental elements in the analysis of the PCOS phenotypes.

Asunto(s)

Etnicidad , Síndrome Metabólico/etnología , Síndrome del Ovario Poliquístico/etnología , Adolescente , Adulto , Andrógenos/sangre , Argentina/epidemiología , Biomarcadores/sangre , Índice de Masa Corporal , Chile/epidemiología , Estudios Transversales , Dislipidemias/diagnóstico , Dislipidemias/etnología , Ayuno/sangre , Femenino , Gonadotropinas/sangre , Humanos , Hiperglucemia/diagnóstico , Hiperglucemia/etnología , Hipertensión/diagnóstico , Hipertensión/etnología , Modelos Logísticos , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Análisis Multivariante , Oportunidad Relativa , Fenotipo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Prevalencia , Factores de Riesgo , Ultrasonografía , Adulto Joven

RESUMEN

OBJECTIVE: To assess gonadotrophin secretion, ovarian steroid production and ovarian reserve in PCOS women during the onset of reproductive decline, in order to characterize their ovarian function at this age. STUDY DESIGN: Forty PCOS patients and 35 healthy women (35-40 years of age) were included. Clinical history, anthropometry, transvaginal ultrasound and a leuprolide acetate test (10 µg/kg s.c.) were performed. Gonadotrophins, steroid hormones, SHBG, inhibin B and AMH were determined. RESULTS: Basal and peak LH levels were similar in both groups. Basal and peak FSH levels were significantly higher in the control group. Androgens, peak oestradiol, ovarian volume, antral follicle count and AMH levels were significantly higher in PCOS patients. CONCLUSION: These observations suggest that during late reproductive age, gonadotrophin secretion in women with PCOS is clearly different from that observed in control women and may also differ from that of younger PCOS patients. New features like normal LH and lower FSH levels associated with a higher ovarian reserve may give a different reproductive profile to these women.

Asunto(s)

Envejecimiento/fisiología , Ovario/fisiopatología , Síndrome del Ovario Poliquístico/fisiopatología , Adulto , Hormona Antimülleriana/sangre , Estudios de Casos y Controles , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Ovario/citología , Síndrome del Ovario Poliquístico/sangre

RESUMEN

Prenatal exposure to excess testosterone induces reproductive disturbances in both female and male sheep. In females, it alters the hypothalamus-pituitary-ovarian axis. In males, prenatal testosterone excess reduces sperm count and motility. Focusing on males, this study tested whether pituitary LH responsiveness to GNRH is increased in prenatal testosterone-exposed males and whether testicular function is compromised in the testosterone-exposed males. Control males (n=6) and males born to ewes exposed to twice weekly injections of 30  mg testosterone propionate from days 30 to 90 and of 40  mg testosterone propionate from days 90 to 120 of gestation (n=6) were studied at 20 and 30 weeks of age. Pituitary and testicular responsiveness was tested by administering a GNRH analog (leuprolide acetate). To complement the analyses, the mRNA expression of LH receptor (LHR) and that of steroidogenic enzymes were determined in testicular tissue. Basal LH and testosterone concentrations were higher in the testosterone-exposed-males. While LH response to the GNRH analog was higher in the testosterone-exposed males than in the control males, testosterone responses did not differ between the treatment groups. The testosterone:LH ratio was higher in the control males than in the testosterone-exposed males of 30 weeks of age, suggestive of reduced Leydig cell sensitivity to LH in the testosterone-exposed males. The expression of LHR mRNA was lower in the testosterone-exposed males, but the mRNA expression of steroidogenic enzymes did not differ between the groups. These findings indicate that prenatal testosterone excess has opposing effects at the pituitary and testicular levels, namely increased pituitary sensitivity to GNRH at the level of pituitary and decreased sensitivity of the testes to LH.

Asunto(s)

Hiperplasia Suprarrenal Congénita/metabolismo , Modelos Animales de Enfermedad , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Luteinizante/metabolismo , Hipófisis/metabolismo , Testículo/metabolismo , Testosterona/metabolismo , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/etiología , Animales , Animales Endogámicos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/análogos & derivados , Leuprolida/farmacología , Hormona Luteinizante/sangre , Masculino , Hipófisis/efectos de los fármacos , Síndrome del Ovario Poliquístico/fisiopatología , Embarazo , Complicaciones del Embarazo/fisiopatología , Distribución Aleatoria , Receptores de HL/genética , Receptores de HL/metabolismo , Maduración Sexual , Oveja Doméstica , Esteroides/biosíntesis , Testículo/efectos de los fármacos , Testosterona/sangre , Propionato de Testosterona

RESUMEN

Polycystic ovary syndrome is recognized as a risk factor for the development of type 2 diabetes and metabolic syndrome. The prevalence of the condition is 6 to 10 percent in different populations. Its etiology is not well known and there are genetic and epigenetic phenomena involved. Due to its association with insulin resistance, it has been incorporated as another component of Reaven plurimetabolic syndrome. Therefore polycystic ovary syndrome evolved from an ovarian disease to a multisystem disorder and it must be considered a public health problem.

Asunto(s)

Humanos , Femenino , Síndrome del Ovario Poliquístico/fisiopatología , Síndrome del Ovario Poliquístico/patología

RESUMEN

The reprograming effects of prenatal testosterone (T) treatment on postnatal reproductive parameters have been studied extensively in females of several species but similar studies in males are limited. We recently found that prenatal T treatment increases Sertoli cell number and reduced spermatogenesis in adult rams. If such disruptions are manifested early in life and involve changes in testicular paracrine environment remain to be explored. This study addresses the impact of prenatal T excess on testicular parameters in infant males, including Sertoli cell number and expression of critical genes [FSH receptor (FSHR), androgen receptor (AR), transforming growth factor beta 1 (TGFB1), 3 (TGFB3), transforming growth factor beta type 1 receptor, (TGFBR1), and anti-Müllerian hormone (AMH)] modulating testicular function. At 4 week of age, male lambs born to dams treated with 30 mg of T propionate twice weekly from day 30 to 90, followed by 40 mg of T propionate from day 90 to 120 of pregnancy (T-males), had a higher number of Sertoli cells/testis (P = 0.035) than control males (C-males) born to dams treated with the vehicle. While no differences were observed in the expression of FSHR and TGFB3, testicular TGFBR1 expression was found to be lower in T-males (P = 0.03) compared to C-males. Expression level of AMH, TGFB1, and AR also tended to be lower in T-males. These findings provide evidence that impact of fetal exposure to T excess is evident early in postnatal life, mainly characterized by an increase in Sertoli cell number. This could explain the testicular dysfunction observed in adult rams.

Asunto(s)

Efectos Tardíos de la Exposición Prenatal , Células de Sertoli/efectos de los fármacos , Testículo/efectos de los fármacos , Testosterona/farmacología , Animales , Recuento de Células , Femenino , Desarrollo Fetal/efectos de los fármacos , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Masculino , Embarazo , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Receptores de HFE/genética , Receptores de HFE/metabolismo , Células de Sertoli/citología , Células de Sertoli/metabolismo , Ovinos , Espermatogénesis/efectos de los fármacos , Testículo/citología , Testículo/crecimiento & desarrollo , Testosterona/sangre , Factor de Crecimiento Transformador beta3/genética , Factor de Crecimiento Transformador beta3/metabolismo

RESUMEN

OBJECTIVE: To evaluate the placental activity of steroid sulfatase (STS), 3ß-hydroxysteroid dehydrogenase type 1 (3ß-HSD-1) and P450 aromatase (P450arom) in polycystic ovarian syndrome (PCOS) compared to normal pregnant women. DESIGN: Twenty pregnant women with PCOS and 30 control pregnant women who delivered at term were studied. Samples of placental tissue and cord blood were obtained after delivery. A maternal blood sample was obtained during the 34th week of gestation. In placental tissue, the activities of STS, 3ß-HSD-1 and P450arom were evaluated. In the blood samples, progesterone, DHEAS, DHEA, androstenedione, testosterone, estrone, estradiol and total estriol were determined. RESULT: In placental tissue from women with PCOS, higher 3ß-HSD-1 and lower P450 aromatase activities were observed compared to control women. Moreover, women with PCOS showed higher androstenedione and testosterone concentrations compared to normal pregnant women (p=0.016 and p=0.025, respectively). In cord blood, female newborns of women with PCOS exhibited lower androstenedione and higher estriol concentrations compared to daughters of control women (p=0.038; p=0.031, respectively). CONCLUSION: These data suggest that placental tissue from women with PCOS shows changes in the activities of two important enzymes for steroid synthesis, higher 3ß-HSD-1 and lower P450, which could increase androgen production during pregnancy.

Asunto(s)

17-Hidroxiesteroide Deshidrogenasas/metabolismo , Aromatasa/metabolismo , Placenta/enzimología , Síndrome del Ovario Poliquístico/enzimología , Complicaciones Neoplásicas del Embarazo/enzimología , Esteril-Sulfatasa/metabolismo , Adulto , Androstenodiona/sangre , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Masculino , Síndrome del Ovario Poliquístico/sangre , Embarazo , Complicaciones Neoplásicas del Embarazo/sangre , Testosterona/sangre , Adulto Joven

RESUMEN

Background: Polycystic ovary syndrome (PCOS) is a common endocrine metabolic dysfunction closely associated with insulin resistance and obesity, which predisposes to pregnancy complications and prenatal programming of the offspring. The aim of this review is to report our experience in PCOS patients who became pregnant and were followed during the whole pregnancy. Firstly, we analyzed the effect of pregnancy on PCOS pathophysiology and secondly the role of PCOS in pregnancy outcomes. Regarding the firstpoint, during normal pregnancy a progressive insulin resistance, serum lipid changes and an increase in androgen levels is observed, which is exacerbated in the PCOS condition. This adverse intrauterine environment could have a prenatal programming effect with detrimental consequences for female or male fetuses. Regarding the second point, PCOS is associated with an increased risk for maternal complications such as gestational diabetes (GDM) and pregnancy-induced hypertension. Moreover, these adverse pregnancy outcomes are more frequently associated with an increase in low birth weight and high birth weight newborns. According to our clinical experience, PCOS patients who became pregnant and were not treated with metformin during the whole pregnancy, showed a higher prevalence of gestational diabetes and SGA newborns, which was improved with metformin treatment. In summary, pregnancy may constitute a period in which an abnormal condition is established or aggravated in the fetus of a PCOS mother. Moreover, PCOS enhanced adverse obstetric and neonatal outcomes.

Asunto(s)

Animales , Femenino , Humanos , Masculino , Embarazo , Síndrome del Ovario Poliquístico/complicaciones , Complicaciones del Embarazo , Peso al Nacer/fisiología , Diabetes Gestacional/etiología , Feto/embriología , Modelos Animales , Resultado del Embarazo

RESUMEN

BACKGROUND: The polycystic ovary syndrome (PCOS) is a hyperandrogenic disorder that arise from a combination of genetic and environmental factors. AIM: To assess the role of the androgen receptor (AR) CAG repeat polymorphism in the metabolic and reproductive features in daughters of women with PCOS (PCOSd). METHODS: Sixty-seven PCOSd and 60 daughters of control women (Cd) were studied in early stages of sexual development. Sex steroids, glucose, insulin and lipids were determined. The AR CAG repeat sizes and X-chromosome inactivation (XCI) were analyzed. RESULTS: PCOSd and Cd had similar mean number of CAG repeats and XCI pattern. In PCOSd and Cd, methylation-weighted biallelic means CAGn (mwCAGn) was not associated with androgen levels. In infants and pubertal PCOSd, mwCAGn was associated with a low concentration of HDL-cholesterol. CONCLUSIONS: AR CAG repeat polymorphism appears to be unrelated with serum androgen levels. However, the short mwCAGn variant may have a possible impact on the lipid profile in PCOSd.

Asunto(s)

Salud de la Familia , Madres , Síndrome del Ovario Poliquístico/genética , Polimorfismo Genético , Receptores Androgénicos/genética , Repeticiones de Trinucleótidos , Inactivación del Cromosoma X , Adolescente , Desarrollo del Adolescente , Andrógenos/sangre , Niño , Desarrollo Infantil , Preescolar , Chile , HDL-Colesterol/sangre , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Leucocitos/metabolismo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Receptores Androgénicos/metabolismo

RESUMEN

CONTEXT: We have previously described increased serum levels of anti-Müllerian hormone (AMH) and stimulated insulin in daughters of women with polycystic ovary syndrome (PCOS), suggesting that these girls may have an altered ovarian follicular development which may be modulated by insulin. However, the specific relationship between serum AMH and insulin levels during each Tanner stage of puberty in this cohort has not been established. OBJECTIVE: The aim of our study was to establish the relationship between AMH and poststimulated insulin serum concentrations during each stage of puberty in daughters of women with PCOS (PCOSd), compared to daughters of control women (Cd). DESIGN: We studied 135 PCOSd and 93 Cd classified according to their Tanner stage. Gonadotrophins, sex steroids, sex hormone-binding globulin (SHBG), and AMH were determined in a fasting sample. Ovarian volume was measured by pelvic ultrasound. In addition, in both groups we performed an oral glucose tolerance test with measurements of glucose and insulin. RESULTS: Anti-Müllerian hormone levels were significantly higher in PCOSd compared to Cd at all Tanner stages. Daughters of women with PCOS having AMH concentrations greater than 2 standard deviation (SD) above the mean AMH value for the Cd group showed decreased serum follicle-stimulating hormone (FSH) concentrations and increased stimulated levels of insulin during Tanner stages I, II, and III. CONCLUSIONS: Anti-Müllerian hormone levels are increased in PCOSd during all stages of puberty. We suggest that those PCOSd with the highest AMH levels probably represent a group of girls with more severe ovarian dysfunction and metabolic derangements.

Asunto(s)

Hormona Antimülleriana/sangre , Insulina/sangre , Síndrome del Ovario Poliquístico/sangre , Pubertad/sangre , Adolescente , Androstenodiona/sangre , Glucemia/metabolismo , Niño , Estudios de Cohortes , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Núcleo Familiar , Ovario/fisiología , Síndrome del Ovario Poliquístico/patología , Embarazo , Globulina de Unión a Hormona Sexual/análisis , Estadísticas no Paramétricas , Testosterona/sangre