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531.
Hannema SE Scott IS Rajpert-De Meyts E Skakkebaek NE Coleman N Hughes IA 《The Journal of pathology》2006,208(4):518-527
The complete androgen insensitivity syndrome (CAIS), caused by mutations in the androgen receptor (AR) gene, is associated with abnormal testicular development and an increased risk of germ cell malignancy. Previous histological studies in CAIS have selected patients purely on the basis of clinical diagnosis and were mostly based on small numbers, many of whom were post-pubertal. Here, we present 44 cases of CAIS, each with molecular pathological confirmation of an AR mutation. The median age at gonadectomy was 5.5 years (5.5; IQR 1-13). We have been able, therefore, to investigate testicular development in infancy, childhood and puberty, and estimate the incidence of premalignant change in this series. In addition, we have investigated whether the presence of epididymides and/or vasa deferentia in CAIS, previously shown to be associated with residual activity of mutant ARs, is related to a particular testicular phenotype. Epididymides/vasa deferentia were present in 36% of cases and these patients showed varying degrees of seminiferous tubule maturation at puberty above those without epididymides/vasa deferentia (p = 0.003). There were no other histological differences between these patient groups. In both groups, features of testicular degeneration and dysgenesis were present and germ cell development was delayed, with prolonged expression of the gonocyte markers, placental-like alkaline phosphatase and activator protein-2gamma. Germ cell numbers rapidly declined after the first year of life (R(2) = 0.42). Only two cases of carcinoma in situ were identified in our study and both patients were postpubertal (17 and 53 years). From these results and the literature, we conclude that the risk of premalignant change in germ cells is low before and during puberty. Patients can be advised, therefore, that gonadectomy can be delayed to allow for a natural puberty, with low risk of malignant transformation. Our study only included one patient over 18 years, so we cannot comment on the risk of malignant transformation in later life. 相似文献
532.
533.
Frederiksen H Aksglaede L Sorensen K Skakkebaek NE Juul A Andersson AM 《Environmental research》2011,111(5):656-663
Background
Phthalates are a group of chemicals with widespread use in the industrial production of numerous consumer products. They are suspected to be involved in male reproductive health problems and have also been associated with several other health problems in children including obesity and asthma.Objectives
To study the urinary excretion of phthalate metabolites in Danish children recruited from the general population, and to estimate the daily intake of phthalates in this segment of the population.Method
One 24 h urine sample and to consecutive first morning urine samples were collected from 129 healthy Danish children and adolescents (range 6–21 yrs). The concentrations of 11 phthalate metabolites of 5 different phthalate diesters were analyzed by liquid chromatography–tandem mass spectrometry.Results
The analyzed metabolites were detectable in almost all 24 h urine samples. The median concentrations of monoethyl phthalate (MEP), monobenzyl phthalate (MBzP) and the sums of the two monobutyl phthalate isoforms (∑MBP(i+n)), metabolites of di-(2-ethylhexyl) phthalate (∑DEHPm) and of di-iso-nonyl phthalate (∑DiNPm) were 29, 17, 111, 107 and 31 ng/mL, respectively. The youngest children were generally more exposed to phthalates than older children and adolescents (except diethyl phthalate (DEP)). Boys were more exposed than girls. The median estimated daily intake of phthalate diesters was: 4.29 (dibutyl phthalate isoforms (DBP(i+n))), 4.04 (DEHP), 1.70 (DiNP), 1.09 (DEP) and 0.62 (butylbenzyl phthalate (BBzP)), all calculated as μg/kg body weight/24 h. Between 40% and 48% of the absolute amount of phthalate metabolites excreted over 24 h were excreted in first morning urine voids.Conclusion
Danish children are exposed simultaneously to multiple phthalates. The highest exposure levels were found for DBP(i+n) and DEHP, which in animal models are the known most potent anti-androgenic phthalates. The combined exposure to the two isoforms of DBP, which have similar endocrine-disrupting potencies in animal models, exceeded the TDI for di-n-butyl phthalate (DnBP) in several of the younger children. 相似文献534.
535.
Suomi AM Main KM Kaleva M Schmidt IM Chellakooty M Virtanen HE Boisen KA Damgaard IN Kai CM Skakkebaek NE Toppari J 《The Journal of clinical endocrinology and metabolism》2006,91(3):953-958
CONTEXT: Hormonal dysregulation has been suggested to be one of many etiological factors of cryptorchidism. OBJECTIVES: The objective of this study was to assess the hypothalamic-pituitary-testicular axis in cryptorchid boys during the postnatal hormonal surge. DESIGN: This was a prospective, longitudinal, population-based study. SETTING: The study was performed at two primary obstetric centers. PARTICIPANTS: Study participants included 388 Finnish and 433 Danish boys (88 and 34 with cryptorchidism, respectively). Interventions: Clinical examinations were performed at 0 and 3 months. Blood samples were taken at 3 months. MAIN OUTCOME MEASURES: The main outcome measures were testis position and reproductive hormone levels. RESULTS: Finnish cryptorchid boys had significantly higher FSH [1.59 (0.50-3.53) vs. 1.30 (0.49-2.92) IU/liter; P < 0.0001] and lower inhibin B [426 (254-770) vs. 459 (266-742) pg/ml; P < 0.015] levels than Finnish control boys [median (2.5th-97.5th percentiles)]. Danish cryptorchid boys had higher FSH levels than controls [1.47 (0.54-3.89) vs. 1.18 (0.41-3.04) IU/liter; P = 0.018]. Inhibin B levels in healthy Danish boys were lower than those in Finnish boys [380 (233-637) pg/ml; P < 0.0001] and were not reduced in Danish crypt-orchid boys [392 (236-672) pg/ml; P = 0.851]. Changes in hormone levels were strongest in boys with severe, persistent cryptorchidism, but were also detectable in mild and transient cryptorchidism. Effects on Leydig cell function were subtle, with an increase in LH in Finnish (but not Danish) cryptorchid boys vs. controls [1.97 (0.77-5.91) vs. 1.75 (0.58-4.04) IU/liter; P < 0.021], but testosterone levels remained within the normal range. CONCLUSIONS: Our results support the hypothesis that cryptorchidism is associated with a primary testicular disorder, which could be a cause or a consequence of cryptorchidism. This malfunction is reflected by low inhibin B production in the Finnish cohort and high gonadotropin drive in both the Finnish and Danish cohorts. 相似文献
536.
Virtanen HE Tapanainen AE Kaleva MM Suomi AM Main KM Skakkebaek NE Toppari J 《The Journal of clinical endocrinology and metabolism》2006,91(12):4862-4865
CONTEXT: Cryptorchidism is the most common malformation in newborn boys. Maternal diabetes has previously been suggested to be a risk factor for this disorder in one epidemiological study. OBJECTIVE: Evaluation of the prevalence of maternal glucose metabolism disorders during pregnancy in newborn boys having normal testicular descent or congenital cryptorchidism. DESIGN: Postnatal analysis of maternal history concerning glucose metabolism abnormalities during pregnancy among cryptorchid and healthy Finnish boys. SETTING AND PARTICIPANTS: The material of this case-control study comprises 1163 boys with normal testicular descent at birth and 125 boys with congenital cryptorchidism. All these singleton Finnish boys were born in Turku University Central Hospital (1997-2001) and were examined at birth and/or at the expected date of delivery. MAIN OUTCOME MEASURES: Information about maternal diabetes diagnosis and abnormality of the result of a 2-h 75-g oral glucose tolerance test during pregnancy were obtained from the hospital records after delivery. RESULTS: After adjustment for possible confounding factors, i.e. maternal smoking during pregnancy, maternal age at delivery, and risk factors of cryptorchidism, e.g. prematurity and weight for gestational age, abnormal maternal glucose metabolism was significantly more common in the group of cryptorchid boys [diet-treated gestational diabetes, P = 0.0001; odds ratio, 3.98 (95% confidence interval, 1.97-8.05); diet-treated gestational diabetes or only an abnormal result in oral glucose tolerance test, P = 0.0016; odds ratio, 2.44 (95% confidence interval, 1.40-4.25)] when compared with boys with normal testicular descent. CONCLUSIONS: Mildly abnormal glucose metabolism during pregnancy was associated with an increased risk for congenital cryptorchidism. The mechanism remains to be elucidated. 相似文献