Patricia Ferrari

Cryptorchidism at birth in Nice area (France) is associated with higher prenatal exposure to PCBs and DDE, as assessed by colostrum concentrations

BACKGROUND Since fetal exposure to anti-androgenic and/or estrogenic compounds has adverse effect on animal reproduction, such exposure could be harmful to human fetus. Data are scarce on cryptorchidism and human exposure to endocrine disruptors. METHODS We performed a prospective case-control study to assess the incidence of cryptorchidism and fetal exposure to selected chemicals in the Nice area. One hundred and fifty-one cord bloods (67 cryptorchid, 84 tightly matched controls) and 125 colostrums (56 for cryptorchid and 69 for controls) were screened for xenobiotics, including anti-androgenic dichloro-diphenyl-trichloro-ethylene (DDE), polychlorinated biphenyls (PCBs), and dibutylphthalate (and metabolite monobutylphthalate, mBP). RESULTS Median concentrations in colostrum were higher, although not statistically significantly, in cryptorchid versus controls. Cryptorchid boys were more likely to be classified in the most contaminated groups in colostrum for DDE, Sigma PCBs and the composite score PCB + DDE. The same trend, but again not statistically significantly was observed for mBP. Odds ratio for cryptorchidism was increased for the highest score of Sigma PCB, with a trend only for DDE and Sigma PCB + DDE versus the lowest score of those components. CONCLUSIONS Our results support an association between congenital cryptorchidism and fetal exposure to PCBs and possibly DDE. Higher concentrations in milk could be a marker of higher exposure or for an impaired detoxification pattern in genetically predisposed individuals.

Unconjugated bisphenol A cord blood levels in boys with descended or undescended testes

BACKGROUND Human toxicity of bisphenol A (BPA), a weak estrogenic environmental endocrine disrupting compound, widely used in plastics, baby bottles, cans and dental sealants, is under investigation. Fetal or perinatal exposure in rodents is associated with programmed adult reproductive diseases. Human epidemiological studies remain scarce, especially concerning testicular development. We have investigated the relationship between fetal exposure to BPA and cryptorchidism. METHODS Using a radioimmunoassay performed after extraction, validated by high-performance liquid chromatography and mass spectrometry, active levels of unconjugated BPA (uBPA) in cord blood (CB) were measured in 152 boys born after 34 weeks gestation, with cryptorchid or descended testes. RESULTS Active uBPA was detectable in all CB samples, with values in the control group (n = 106) of 0.14-4.76 ng/ml, median: 0.9 ng/ml; mean ± SD: 1.12 ng/ml ± 0.86 ng/ml, which did not differ from cryptorchid boys (n = 46, 1.26 ± 1.13 ng/ml, P = 0.38). uBPA in controls correlated with CB inhibin B (P < 0.01) and total testosterone (P < 0.05), and with maternal milk polychlorinated bisphenyl 138 (P < 0.03). uBPA did not correlate with clinical maternal or fetal parameters or with other steroid or polypeptide CB hormones assessed. CONCLUSIONS The presence of uBPA in all CB samples suggests placental transfer and fetal exposure. Similar uBPA levels in the control and cryptorchid groups make the participation of fetal exposure to uBPA in the physiopathology of undescended testes unlikely. However, the observed nanomolar uBPA concentrations support assessment of epidemiological relationships between CB uBPA and other human diseases.

Exposure to selected endocrine disruptors and neonatal outcome of 86 healthy boys from Nice area (France)

In utero and lactational exposure to endocrine disruptors is thought to be potentially harmful on fetal and infant development. Data of exposure in France is scarce. This is a prospective study with (1) collection of 84 cord bloods (CB) and 69 milks from 86 mothers delivering healthy boys (gestational age >or= 34 weeks) at two maternity wards in Southern France, between 2002 and 2005 and (2) screening for 15 xenobiotics with anti-androgenic and/or estrogenic effects: DDE, 7 PCBs, dibutylphthalate and its metabolite mBP, HCB, lindane, linuron, procymidone and vinclozoline. Correlations were made with delivery and neonatal outcomes. All CB and milks were contaminated by one or more xenobiotics (mainly PCBs, DDE, HCB, and phthalates) with good correlation between CB and milk concentrations. Compared to other geographical areas, exposure was usually in the lower bracket. Milk [PCB180] was associated with lower birth weight. Infant head circumference correlated negatively with [HCB] and positively with [mBP] in CB. There was a similar but not significant trend for birth weight and length. [DDE] in milk was higher in older mothers and in women born in Africa. In utero and lactational exposure is ubiquitous in our area. Contamination of milk with HCB, mBP, and PCB 180 showed weak correlations with infant growth. This snapshot of exposure in an area with no major industry will serve for further monitoring.

Cord Blood Thyroid Tests in Boys Born With and Without Cryptorchidism: Correlations with Birth Parameters and In Utero Xenobiotics Exposure

BACKGROUND In utero exposure to environmental chemicals can result in reproductive toxicity via endocrine disruption mechanisms. Whether some of those contaminants also have an impact on fetal thyroid function or pathways, and, thus, potentially on neuropsychological development, is still debated. METHODS We used samples from a cord blood (CB) and milk bank, established for a research on cryptorchidism and xenobiotic exposure to compounds known for their anti-androgenic and/or estrogenic activity, to study CB thyroid tests and their correlation with CB and milk xenobiotics concentrations in boys born in Nice area. RESULTS No difference was found in thyroid tests between 60 cryptorchid boys and 76 matched controls (median thyroid stimulating hormone 5.97 vs. 6.55 mUI/L, free thyroxine [fT4] 13.1 vs. 12.9 pmol/L, free triiodothyronine [fT3] 1.9 vs. 2.1 pmol/L), with no influence of season of birth, gestational age, maternal smoking, or mode of delivery (except for higher fT4 in control boys born vaginally). FT4 was correlated with fetal growth only in cryptorchid boys. Since we had previously shown differences between cryptorchid and controls exposure, we studied correlations of thyroid tests with xenobiotics in control boys only. All tested CB or maternal milk was contaminated by one or more selected xenobiotics, mainly polychlorinated biphenyls (PCBs), dichloro diphenyl dichloroethylène (DDE), dibutylphthalate, hexachlorobenzene, and bisphenol A. We found a significant negative correlation between fT4 and concentrations of PCB118, PC180, and DDE in milk (respectively r = -0.342, p < 0.03, r = -0.296, p = 0.031, r = -0.315, p = 0.016), persisting after adjustment for mode of delivery. There was a significant positive correlation of fT3 with milk concentrations of PCB138, PCB153, ΣPCB, and dibutylphthalate (respectively r = 0.31, p = 0.016, r = 0.28, p = 0.029; r = 0.34, p = 0.0079 and r = 0.272, p = 0.0295), with a trend for PCB180 (r = 0.259, p = 0.061). There was no correlation of thyroid stimulating hormone with any of the measured xenobiotics, except for a weak negative trend with CB bisphenol A (r = -0.25, p = 0.077). CONCLUSIONS CB thyroid tests are within normal range in cryptorchid boys, similar to controls. Our data in controls suggest a possible weak correlation between in utero exposure to some xenobiotics (PCBs, DDE) and fT3 and fT4 CB concentrations, with usually negative correlations with fT4 and positive with fT3 concentrations, which we speculate could suggest an impact on deiodinases.

Statut iodé et fonction thyroïdienne chez 330 femmes de la région niçoise évaluées en deuxième partie de grossesse

BACKGROUND Iodine deficiency (ID) is still common in Western Europe and its prevention remains a challenge, particularly during pregnancy. METHODS We studied 330 pregnant women in the third trimester of pregnancy for ioduria (UIE) and thyroid tests (TSH, fT4). We collected information on personal history of thyroid disease and treatment with thyroid hormones or iodinated pregnancy tablets. RESULTS AND DISCUSSION Median UIE was 64 microg/l, reflecting inadequate iodine intake in our population. According to the UIE threshold used for diagnosis (100 to 150 microg/l), ID was present in 74.3% to 85.8% of women; 5.4% had excessive iodine intake, including one taking iodine fortified tablets. Only 8.8% had adequate intake, suggesting that current strategies to eradicate ID are inefficient in our country. Among the 22 women taking iodine supplements, only three had adequate UIE and four had UIE below the detection level, which could suggest either poor compliance or insufficient supplementation. Median fT4 was 12.3pmol/l (8-20.1) and TSH 1.93mUI/l (0.24-6.57). We used different thresholds proposed in the literature to diagnose: hypothyroxinemia: 41.2% were less than 12pmol/l, 10% less than 10.3pmol/l and 1.8% less than 9pmol/l (lower limit of our reference range); subclinical hypothyroidism: 26.3% had TSH greater than 2.5 or 3.9% greater than 4mUI/L, 1.2 to 13% had combined low fT4 (<9pmol/l or <12pmol/) and higher TSH (>2.5mUI/l). There was no correlation between UIE and thyroid tests, nor maternal predicting factors for ID. CONCLUSION ID is common in our population. The wide range of hypothyroxinemia and subclinical hypothyroidism prevalence should also trigger reflection of diagnostic thresholds and therapeutic intervention.

Relative Impact of Iodine Supplementation and Maternal Smoking on Cord Blood Thyroglobulin in Pregnant Women with Normal Thyroid Function

Objective: To assess the impact on cord blood (CB) thyroglobulin (Tg) of early iodine supplementation during pregnancy. Methods: A total of 111 healthy pregnant women with normal thyroid function were included in a prospective randomized study and divided into two groups with (150 µg/day) or without iodine supplementation started during the first trimester. Maternal smoking was assessed qualitatively by self-reported statements and quantitatively by cotininuria. Exhaustive thyroid tests were performed at delivery in the mother and in CB. Results: Third-trimester ioduria documented compliance with iodine supplementation (160 vs. 76 µg/l in controls). CB Tg was not different between the iodine and control groups (median 77 vs. 79.5 ng/ml, respectively) and did not correlate with maternal ioduria. CB Tg was higher in newborns from smoking mothers (114 vs. 64.7 ng/ml) and correlated with self-reported smoking status more than with maternal cotininuria. Nonsmokers had no difference in CB Tg whether they took iodine supplementation or not, as opposed to smokers, who tended to benefit from supplementation. Conclusions: Iodine supplementation does not significantly impact CB Tg in healthy nonsmoker pregnant women selected for normal thyroid function, as opposed to maternal smoking. CB Tg appears to be a marker of in utero tobacco exposure. In areas of mild iodine deficiency, iodine supplementation could especially benefit the fetuses of smokers.

Postpubertal Persistent Hyperestrogenemia in McCune-Albright Syndrome: Unilateral Oophorectomy Improved Fertility but Detected an Unexpected Borderline Epithelial Ovarian Tumor

BACKGROUND McCune-Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. CASE A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization-induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. SUMMARY AND CONCLUSION Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented.

Contents Vol. 1, 2012

Maria Alevizaki, Athens Ana Aranda, Madrid Rebecca Bahn, Rochester, Minn. Paul Banga, London Luigi Bartalena, Varese Bernadette Biondi, Naples Anita Boelen, Amsterdam Georg Brabant, Lubeck Henning Dralle, Halle Murat Erdogan, Ankara Creswell J. Eastman, Westmead, N.S.W. Valentin Fadeyev, Moscow Ulla Feldt-Rasmussen, Copenhagen Laszlo Hegedus, Odense George J. Kahaly, Mainz Rui Maciel, São Paolo Ana Luiza Maia, Porto Alegre Jens Mittag, Stockholm Ralf Paschke, Leipzig Simon Pearce, Newcastle-upon-Tyne Robin Peeters, Rotterdam Kris Poppe, Bruxelles Samuel Refetoff , Chicago, Ill. Jacques Samarut, Lyon Pilar Santisteban, Madrid YoungKee Shong, Seoul Jan Smit, Leiden Mark Vanderpump, London Th eo Visser, Rotterdam Paolo Vitti, Pisa Graham Williams, London Shunichi Yamashita, Nagasaki Mariastella Zannini, Naples Luca Persani, Milan (Translational Th yroidology)