Katharina M Main

IT University of Copenhagen, København, Capital Region, Denmark

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Publications (125)559.05 Total impact

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    ABSTRACT: Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n = 8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.
    No preview · Article · Jan 2016 · Scandinavian journal of clinical and laboratory investigation
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    ABSTRACT: Background: Phthalates comprise a large class of chemicals used in a variety of consumer products. Several have anti-androgenic properties and in rodents prenatal exposure has been associated with reduced anogenital distance (AGD); the distance from the anus to the genitals in male offspring. Few human studies have been conducted but associations between the anti-androgenic phthalates and male AGD have been reported. Objective: To study the association between phthalate exposure in late pregnancy in Danish women pregnant in 2010-2012 and AGD in their infants at 3 months of age (N=273). Methods: In the Odense child cohort urinary concentrations of 12 phthalate metabolites of di-ethyl, di-n-butyl-, di-iso-butyl-, di-(2-ethylhexyl)-, butyl-benzyl- and di-iso-nonyl phthalate (DEP, DnBP, DiBP, DEHP, BBzP and DiNP, respectively) were measured among 245 mothers to boys at approximately gestational week 28 (range 20.4-30.4) and adjusted for osmolality. AGD, penile width and weight were measured 3 months after the expected date of birth. Associations between prenatal phthalate exposure and AGD and penile width were estimated using multivariable linear regression adjusting for age and weight-for-age standard deviation score. Results: Phthalate levels were lower in this population than in a recent Swedish in which phthalates were measured in first trimester. No consistent associations were seen between any prenatal phthalate exposure and AGD or penile width. Most associations were negative for exposures above the first quartile, and for ln-transformed exposures modeled as continuous variables, but there were no consistent dose-response patterns, and associations were not statistically significant (p > 0.05) CONCLUSION: We found no significant trends towards shorter AGD in boys with higher phthalates exposures in this low exposed Danish population.
    Full-text · Article · Dec 2015 · Environmental Health Perspectives
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    ABSTRACT: Development of human gonads is a sex-dimorphic process which evolved to produce sex-specific types of germ cells. The process of gonadal sex differentiation is directed by the action of the somatic cells and ultimately results in germ cells differentiating to become functional gametes through spermatogenesis or oogenesis. This tightly controlled process depends on the proper sequential expression of many genes and signalling pathways. Disturbances of this process can be manifested as a large spectrum of disorders, ranging from severe disorders of sex development (DSD) to - in the genetic male - mild reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which are essentially the same precursor lesion with morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published since 2006. We present a model for pathogenesis of GCNIS/GDB in TDS/DSD, with the risk of malignancy determined by the presence of the testis-inducing Y-chromosome and the degree of masculinisation. The associations between phenotype and the risk of neoplasia are likely further modulated in each individual by the constellation of the gene polymorphisms and environmental factors.
    No preview · Article · Sep 2015 · Seminars in Cell and Developmental Biology
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    ABSTRACT: Background: Congenital cryptorchidism, i.e. failure of the testicular descent to the bottom of the scrotum, is a common birth defect. The evidence from epidemiological, wildlife, and animal studies suggests that exposure to mixtures of endocrine disrupting chemicals during fetal development may play a role in its pathogenesis. We aimed to assess the association between cryptorchidism and prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), and polybrominated diphenyl ethers (PBDEs). Methods: We conducted a case-control study consisting of 44 cryptorchid cases, and 38 controls operated for inguinal hernia, umbilical hernia, or hydrocele at the Turku University Hospital or Rigshospitalet, Copenhagen in 2002-2006. During the operation a subcutaneous adipose tissue biopsy was taken. Samples were analysed for 37 PCBs, 17 PCDD/Fs and 14 PBDEs by gas chromatography-high-resolution mass spectrometry. Chemical concentrations were adjusted for postnatal variation introduced by differences in duration of breastfeeding, age at the operation, and country of origin with a multiple linear regression. Association between adjusted and unadjusted chemical concentrations and the risk of cryptorchidism were analysed with logistic regression to get an estimate for odds ratio (OR) of cryptorchidism per multiplication of chemical concentrations with ca. 2.71 (Napier's constant). Results: Total-TEq i.e. the WHO-recommended 2,3,7,8-TCDD equivalent quantity of 17 dioxins and 12 dioxin-like PCBs and sum of PCDD/Fs were positively associated with cryptorchidism [OR 3.21 (95 % CI 1.29-9.09), OR 3.69 (95 % CI 1.45-10.9), respectively], when adjusting for country of origin, the duration the child was breastfed, and age at operation. The association between the sum of PCBs and cryptorchidism was close to significant [OR 1.92 (95 % CI 0.98-4.01)], whereas the association between the sum of PBDEs and cryptorchidism was not [OR 0.86 (95 % CI 0.47-1.54)]. There were no associations between unadjusted chemical concentrations and the risk of cryptorchidism. Conclusions: Prenatal exposure to PCDD/Fs and PCDD/F-like PCBs may be associated with increased risk for cryptorchidism. Our finding does not exclude the possibility of an association between the exposure to PBDEs and cryptorchidism.
    Full-text · Article · Sep 2015 · Environmental Health
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    ABSTRACT: Physiological gynaecomastia is common and affects a large proportion of otherwise healthy adolescent boys. It is thought to be caused by an imbalance between estrogen and testosterone, though this is rarely evident in analyses of serum. This study aimed to describe the frequency of physiological gynaecomastia, and to determine possible etiological factors (e.g. auxology and serum hormone levels) in a longitudinal set-up. Design, Settings and Participants: A prospective cohort study of 106 healthy Danish boys (5.8-16.4 years) participated in the longitudinal part of "the COPENHAGEN Puberty Study". The boys were examined every six months during an eight year follow-up. Median number of examinations was 10 (2-15). Blood samples and analysed for FSH, LH, testosterone, estradiol, SHBG, inhibin B, AMH, IGF-I and IGFBP-3 by immunoassays. Auxological parameters, pubertal development and the presence of gynaecomastia were evaluated at each visit. 52 of 106 boys (49 %) developed gynaecomastia of which 10 (19 %) presented with intermittent gynaecomastia. Boys with physiological gynaecomastia reached peak height velocity at a significantly younger age than boys who did not develop gynaecomastia (13.5 vs 13.9 years, p = 0.027), and they had significantly higher serum levels of IGF-I (p = 0.000), estradiol (p = 0.013), free-testosterone (p < 0.001) and FSH (p = 0.030) during pubertal transition. However, no differences in serum LH or in the estradiol to testosterone ratio were found. Gynaecomastia is frequent in pubertal boys. Increased IGF-I levels and pubertal growth appear to be associated, whereas changes in estrogen to testosterone ratio seem negligible.
    No preview · Article · Aug 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: To report normative data on uterine volume and endometrial thickness in girls, according to pubertal stages; to evaluate factors that affect uterine volume; and to compare transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI). Cross-sectional study of a nested cohort of girls participating in The Copenhagen Mother-Child Cohort. General community. One hundred twenty-one healthy girls, aged 9.8-14.7 years. None. Clinical examination, including pubertal breast stage (Tanner classification: B1-B5). Uterine volume: ellipsoid TAUS (n = 112) and 3-dimensional TAUS (n = 111); ellipsoid MRI (n = 61). Endometrial thickness: TAUS (n = 110) and MRI (n = 60). Uterine volume and endometrial thickness were positively correlated with pubertal stages; e.g., ellipsoid TAUS: r = 0.753, and endometrium TAUS: 0.648. In multiple regression analyses, uterine volume was associated with the number of large follicles (TAUS >5 mm) (Beta 0.270); estradiol (E2) (Beta 0.504); and height (Beta 0.341). Volumes from ellipsoid vs. 3-dimensional TAUS were strongly correlated (r = 0.931), as were TAUS and MRI: ellipsoid volume (r = 0.891) and endometrial thickness (r = 0.540). Uterine volume was larger in TAUS compared with MRI; mean difference across the measured range: 7.7 (5.2-10.2) cm(3). Agreement was best for small uteri. Uterine volume and endometrial thickness increased as puberty progressed. Circulating E2 from large follicles was the main contributor to uterine and endometrial growth. The TAUS and MRI assessments of uterus and endometrium were strongly correlated. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jun 2015 · Fertility and sterility
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    ABSTRACT: Context The majority of Turner syndrome (TS) patients suffer from accelerated loss of primordial follicles. Low circulating levels of anti-M )llerian Hormone (AMH) may predict lack of spontaneous puberty in prepubertal girls and imminent premature ovarian insufficiency (POI) in TS women with preserved ovarian function. Objectives To evaluate the association between circulating AMH and ovarian status in TS patient. Design Longitudinal observational cohort study. Setting Tertiary referral centre for paediatric and gynaecologic endocrinology. Participants 120 Turner syndrome patients, aged 0 to 48 years. Main outcome measures Longitudinal measurements of AMH, FSH, LH, estradiol and inhibin B according to age, karyotype (45,X; 45,X/46,XX mosaicism; miscellaneous karyotypes) and ovarian status (group 0: prepubertal; group 1: never ovarian function; group 2: ongoing ovarian function; group 3: loss of ovarian function). Results Ovarian status was highly associated with the TS karyotype; spontaneous puberty: 45,X (3/44 patients), 45,X/46,XX (15/17), miscellaneous (17/42) and POI: 45,X (3/3 patients), 45,X/46,XX (1/15), miscellaneous (8/17). AMH was associated with ovarian status (e.g. group 1: < 2 pmol/L vs. group 2: 19 pmol/L, p<0.001). AMH < 4 pmol/L (corresponding to < -2SD) predicted absent puberty in prepubertal girls and POI in adolescent and adult patients. Conclusion The majority of women with mosaic karyotype 45,X/46,XX had on-going ovarian function in early adulthood. AMH < -2SD predicted failure to enter puberty in young TS girls and imminent POI in adolescent and adult TS patients.
    No preview · Article · May 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Studies of adolescents often use self-assessment of pubertal maturation, the reliability of which has shown conflicting results. We aimed to examine the reliability of child and parent assessments of healthy boys and girls. A total of 898 children (418 girls, 480 boys, age 7.4-14.9 years) and 1173 parents (550 daughters, 623 sons, age 5.6-14.7 years) assessed onset of puberty or development of breasts, genitals, and pubic hair according to Tanner stages by use of a questionnaire and drawings. Physicians' assessments were blinded and set as the gold standard. Percentage agreement, κ, and Kendall's correlation were used to analyze the agreement rates. Breast stage was assessed correctly by 44.9% of the girls (κ = 0.28, r = 0.74, P < .001) and genital stage by 54.7% of the boys (κ = 0.33, r = 0.61, P < .001). For pubic hair stage 66.8% of girls (κ = 0.55, r = 0.80, P < .001) and 66.1% of boys (κ = 0.46, r = 0.70, P < .001) made correct assessments. Of the parents, 86.2% correctly assessed onset of puberty in girls (κ = 0.70, r = 0.71, P < .001) and 68.4% in boys (κ = 0.30, r = 0.37, P < .001). Children who underestimated were younger and children who overestimated older than their peers who made correct assessments. Girls and their parents tended to underestimate, whereas boys overestimated their pubertal stage. Pubertal assessment by the child or the parents is not a reliable measure of exact pubertal staging and should be augmented by a physical examination. However, for large epidemiologic studies self-assessment can be sufficiently accurate for a simple distinction between prepuberty and puberty. Copyright © 2015 by the American Academy of Pediatrics.
    Full-text · Article · Dec 2014 · Pediatrics
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    ABSTRACT: Context: In adult women, Anti-Müllerian hormone (AMH) is produced by small growing follicles, and circulating levels of AMH reflect the number of antral follicles as well as primordial follicles. Whether AMH reflects follicle numbers in healthy girls remains to be elucidated. Objective: To evaluate if serum levels of AMH reflects ovarian morphology in healthy girls. Design: Population-based cohort study. Setting: General community. Participants: 121 healthy girls aged 9.8 - 14.7 years. Main outcome measures: Clinical examination, including pubertal breast stage (Tanner´s classification B1 - 5). Ovarian volume as well as the number and size of antral follicles were assessed by two independent modalities: A) Magnetic resonance imaging (MRI): Ellipsoid volume, follicles ≥ 2mm, and B) Transabdominal ultrasound (TAUS): Ellipsoid- and 3D volume, follicles ≥ 1mm. Circulating levels of AMH, inhibin B, estradiol, FSH and LH were assessed by immunoassays; testosterone and androstenedione by LC-MS/MS. Results: AMH reflected the number of small (MRI 2 - 3mm) and medium (4 - 6mm) follicles (Pearson´s Rho (r) = 0.531 and r = 0.512, p<0.001) but not large follicles (≥ 7mm) (r = 0.109, p=0.323). In multiple regression analysis, small and medium follicles (MRI ≤ 6mm) remained the main contributors to circulating AMH (Beta 0.501, p<0.001) whereas the correlation between AMH and estradiol was negative (Beta -0.318, p=0.005). In early puberty (B1 - B3), the number of AMH-producing follicles (2 - 6mm) correlated positively with pubertal stages (r=0.453, p=0.001), whereas AMH levels were unaffected (-0.183, p=0.118). Conclusions: Similarly to adult women, small and medium antral follicles (≤ 6mm) were the main contributors to circulating levels of AMH in girls.
    Full-text · Article · Dec 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Prenatal environmental exposures may influence the risk of cardio-metabolic diseases later in life. This study used a multiplex approach to investigate non-fasting serum levels of metabolic markers in a cohort of school-aged children for whom associations between prenatal pesticide exposure and body fat content and blood pressure were previously found to be dependent on paraoxonase1 (PON1) Q192R genotype. In children with the PON1 192 R-allele, leptin, glucagon, and plasminogen activator inhibitor-1 (PAI-1) were positively associated with prenatal pesticide exposure. For PON1 192 QQ-homozygote children none of the biomarkers were significantly affected by prenatal pesticide exposure. In children with the R-allel, leptin was associated with both body fat measures and prenatal pesticide exposure and seems to mediate body fat accumulation in exposed children. These findings support our previous results of an adverse cardio-metabolic risk profile associated with prenatal pesticide exposure in children with the PON1 192 R-allele. Copyright © 2014. Published by Elsevier Inc.
    No preview · Article · Nov 2014 · Reproductive Toxicology
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    ABSTRACT: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Oct 2014 · Fertility and Sterility
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    ABSTRACT: Aimational screening programmes for congenital adrenal hyperplasia now include measuring several adrenal metabolites using highly sensitive liquid chromatography-tandem mass spectrometry. The aim of thisstudy was tocompare neonatal hormonal profiles - whole blood concentrations of 17α-hydroxyprogesterone, androstenedione, and cortisol - with genotypes in 21-hydroxylase deficiency.Methods The study included 62 patients with congenital adrenal hyperplasia born between 1982 and 2012 and 61 random controls born in 1985 and 2005. Patients were grouped according to mutation-based predictions of enzyme impairment. Groups Null and A were salt-wasting (n=35), Group B was simple virilising (n=7) and Group C wasnon-classic(n=20). Dried blood spot samples were retrieved from the Danish Neonatal Screening Biobank.ResultsAll patients with molecular verified 21-hydroxylase deficiency had significantly higher concentrations of 17α-hydroxyprogesterone (p<0.001), androstenedione (p<0.001) anda higher ratio ((17α-hydroxyprogesterone + androstenedione)/cortisol, p<0.05) than controls. Androstenedione showed a higher sensitivity (72%)than 17α-hydroxyprogesterone (12%)to correctly identify Groups B and C.Conclusion There were significant differences in neonatal hormonal profiles between all groups and controls. This confirms that hormonal disturbances are already detectable in both severe and mild forms of congenital adrenal hyperplasia in neonatal life.This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2014 · Acta Paediatrica
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    ABSTRACT: Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5-12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date.
    Full-text · Article · Sep 2014 · Scientific Reports
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    Full-text · Article · Sep 2014 · Nature Reviews Endocrinology
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    ABSTRACT: The influence of sex, age, pubertal development and oral contraceptives on dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), 17α-hydroxyprogesterone (17-OHP), Δ4-androstenedione (Adione), testosterone (T), calculated free testosterone (fT), free androgen index (FAI) and selected ratios in 1798 serum samples from healthy children, adolescents and young adults was evaluated. Samples were analysed by Turboflow-LC-MS/MS. Sex hormone-binding globulin was analysed by immunoassay. All steroid metabolite concentrations were positively associated with age and pubertal development in both sexes and generally higher in males than in females except for Adione. The pubertal rise in T in males was more pronounced compared to females, reflecting contribution from the testes. Ratios between steroid metabolites varied and depended on sex and age. All ratios were lower during infancy compared to later in life. Use of oral contraceptives significantly lowered serum concentrations of all steroid metabolites, fT, FAI, the 17-OHP/Adione, the Adione/T and the DHEA/Adione ratios, but not the DHEA/DHEAS ratio. We provide reference ranges for DHEA, DHEAS, 17-OHP, Adione, T, fT, FAI and selected ratios in relation to sex, age and pubertal development. Use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with disorders of sex development.
    Full-text · Article · Jun 2014 · Clinica Chimica Acta
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    ABSTRACT: Although common reproductive problems, such as male infertility and testicular cancer, present in adult life, strong evidence exists that these reproductive disorders might have a fetal origin. The evidence is derived not only from large epidemiological studies that show birth-cohort effects with regard to testicular cancer, levels of testosterone and semen quality, but also from histopathological observations. Many infertile men have histological signs of testicular dysgenesis, including Sertoli-cell-only tubules, immature undifferentiated Sertoli cells, microliths and Leydig cell nodules. The most severe gonadal symptoms occur in patients with disorders of sexual development (DSDs) who have genetic mutations, in whom even sex reversal of individuals with a 46,XY DSD can occur. However, patients with severe DSDs might represent only a small proportion of DSD cases, with milder forms of testicular dysgenesis potentially induced by exposure to environmental and lifestyle factors. Interestingly, maternal smoking during pregnancy has a stronger effect on spermatogenesis than a man's own smoking. Other lifestyle factors such as alcohol consumption and obesity might also have a role. However, increasing indirect evidence exists that exposure to ubiquitous endocrine disrupting chemicals, present at measurable concentrations in individuals, might affect development of human fetal testis. If confirmed, health policies to prevent male reproductive problems should not only target adult men, but also pregnant women and their children.
    Full-text · Article · Jun 2014 · Nature Reviews Endocrinology
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    ABSTRACT: Background Humans are exposed to tributyltin (TBT), previously used as an antifouling paint in ships, mainly through fish consumption. As TBT is a known obesogen, we studied the association of placenta TBT and other organotin compounds (OTCs) with ponderal index (PI) and growth during the first 18 months of life in boys. Methods In a prospective Finnish study, 110 placenta samples were collected from mothers of boys born in 1997–1999 with (n = 55) and without (n = 55) cryptorchidism. To account for the original study design, linear regression, weighted for sampling fractions of boys with (121/55) and without (5677/55) cryptorchidism from the total cohort, was used to study the association between placenta OTCs and children’s weight, length, growth rates and PI up to 18 months of age. Results Placenta TBT concentrations were above the limit of quantification (LOQ) in 99% of the samples. However, monobutyltin (MBT), dibutyltin (DBT) and triphenyltin (TPhT) concentrations were below LOQ in 90%, 35% and 57% of samples, respectively. Placenta TBT was positively associated (p = 0.024) with weight gain during the first three months of life, but no other significant associations were observed for weight or length gain. Also, no significant associations between placenta OTC concentrations and child length, weight or PI at any time point were found. Conclusions We observed a trend towards higher weight gain from birth to 3 months of age with increasing placenta TBT concentration. These results should be interpreted with caution because obesogenic effects in animal experiments were seen after in-utero TBT exposures to doses that were orders of magnitude higher. Also the number of study subjects included in this study was limited.
    Full-text · Article · Jun 2014 · Environmental Health
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    ABSTRACT: Background: Some phthalates have shown antiandrogenic effects in rat offspring. Premature infants may be exposed to high amounts of specific phthalates during hospitalization, and thus are potentially at risk. Objective: We evaluated longitudinal phthalate exposure and metabolism in full-term (FT) and preterm (PT) infants. Methods: Fifty-eight FT and 67 PT (gestational age, 24.7-36.6 weeks) infants were recruited at birth and followed until 14 months (nine times). Urinary concentrations of metabolites of diethyl phthalate (DEP), dibutyl phthalate isomers (DiBP and DnBP), butylbenzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and diisononyl phthalate (DiNP) were measured in 894 samples. Daily intake and a hazard index for antiandrogenic effects were estimated, and excretion patterns of DEHP and DiNP metabolites were analyzed. Results: Metabolites of BBzP, DiNP, and DEHP were 5-50 times higher at day 7 (D7) and month 1 (M1) in PT than in FT infants. Thereafter, metabolite concentrations were similar between the two groups. The estimated hazard index for combined DiBP, DnBP, BBzP, and DEHP exposures 7 days after birth exceeded the antiandrogenic threshold in > 80% of PT and > 30% of FT infants, and after M2, in 30% of all infants. The excretion pattern of DEHP and DiNP metabolites changed with age. Conclusion: Most PT infants and approximately one-third of healthy FT newborns were exposed to phthalates during early life at a potentially harmful level according to the European Food Safety Authority's recommended limits of daily exposure. Changes in the relative proportions of secondary phthalate metabolites over time were consistent with maturation of infant metabolic pathways during the first year of life. Further research is needed on the health effects of phthalate exposures and the influence of changes in metabolic capacity in neonates and infants.
    Full-text · Article · May 2014 · Environmental Health Perspectives
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    ABSTRACT: Background: Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent. Objectives: We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population. Methods: Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography-tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors. Results: We found that 98% of the men had detectable urinary levels of BPA. Median (5th-95th percentiles) BPA concentration was 3.25 ng/mL (0.59-14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (ptrend ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (-6.7 percentage points, 95% CI: -11.76, -1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results. Conclusions: The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic-pituitary-gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.
    Full-text · Article · May 2014 · Environmental Health Perspectives

  • No preview · Article · Apr 2014

Publication Stats

5k Citations
559.05 Total Impact Points

Institutions

  • 2002-2016
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 2002-2013
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 2006-2011
    • University of Turku
      • Department of Physiology
      Turku, Varsinais-Suomi, Finland
    • Indiana University Bloomington
      Bloomington, Indiana, United States
  • 2009
    • Region Hovedstaden
      Hillerød, Capital Region, Denmark
  • 2008
    • Roskilde University
      Roskilde, Zealand, Denmark
  • 2004
    • Rigshospitalet
      København, Capital Region, Denmark
  • 2001
    • National University (California)
      San Diego, California, United States