Fetal development

Human environmental and dietary exposure to trans-capsaicin—the pungent ingredient in chili peppers—is ubiquitous. Moreover, based on the highly selective agonism of trans-capsaicin for TRPV1 receptors, drug products containing high concentrations of trans-capsaicin are under development as analgesics. For instance, a high-concentration (8% w/ w) pure trans-capsaicin dermal patch (designated NGX-4010) is in advanced clinical evaluation for the management of neuropathic pain of peripheral origin. Our objective was to investigate effects of trans-capsaicin on embryo/fetal development, consequent to maternal exposure, from implantation to closure of the hard palate. trans-Capsaicin was delivered systemically by means of either a patch [NGX-4010 (25, 37.5, or 50 cm2)] to pregnant Sprague-Dawley rats on days of presumed gestation (DGs) 7 through 17, or via a 10% w/ v capsaicin liquid formulation (CLF), at dosages of 3, 6.5 or 13 μl/cm2 applied to a 200-cm2 area on the back on DGs 7 thoug...

Alpha-iso-methylionone, a widely used fragrance ingredient, was evaluated for developmental toxicity in presumed pregnant Sprague-Dawley rats (25/group). Oral dosages of 0, 3, 10, or 30 mg/kg/day alpha-iso-methylionone in corn oil were administered by gavage on gestational days 7 to 17. The presence of spermatozoa and/or a copulatory plug in situ was designated as gestational day. Rats were observed for viability, clinical signs, body weights, and feed consumption. Caesarean sectioning and necropsy occurred on gestational day 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No maternal or fetal deaths occurred. No fragrance ingredient–related clinical signs were observed. Feed consumption, body weight gains, gross tissue changes at necropsy, and caesarean...

The fragrance ingredient 4- tert-butylcyclohexyl acetate (4- tBCHA) was evaluated for potential developmental toxicity in pregnant rats at oral dosages of 0, 40, 160, or 640 mg/kg per d in corn oil on gestational days 7 to 20. Increased salivation was observed at 160 and 640 mg/kg per d. The 640 mg/kg per d dosage was associated with the presence of a red perioral substance, ungroomed, sparse hair coat on the limbs, localized alopecia, reduced feed and body weight gains, or body weight losses, and mortality. Fetal body weights also were reduced at 640 mg/kg per d. This effect was associated with transient delays in fetal development, including significant increases in fetal incidences of moderate enlargement of the renal pelvis and reversible delays in ossification of the caudal vertebrae, fore and hind limb phalanges, and hind limb metatarsals. Maternal and developmental no observable adverse effect levels (NOAELs) were 160 mg/kg per d. It was concluded that 4- tBCHA is not a devel...

Pregnancy is a transformative phase of any woman's life when they face physical, emotional, and psychological changes that can be both challenging and rewarding. These changes may lead to disturbed sleep, edema, fatigue, nausea, back pain which is arise from the physiological adaptations required to support the growing fetus. The study explores the integrated traditional practices –Yoga, music and hymns during pregnancy as complimentary maternal care in enhancing the wellbeing of both mother and baby.  In conclusion, the integrated use of Yoga, music, and hymns in the study indicates improved well-being during pregnancy, enhanced physical abilities like flexibility and strength, and a notable decrease in anxiety, depression, and emotional fluctuations.

The expression of functional receptors for nerve growth factor in insulin-producing cell lines grown in vitro has recently been demonstrated. The possible importance of signals transduced via these receptors in the control of islet maturation has been proposed based on data obtained using an in vitro culture system. To further support this hypothesis, we have studied the expression of Trk-A, the high-affinity receptor for NGF, in vivo during the embryonic and fetal development of the rat pancreas. We have also examined the expression of NGF during the same period. Immunohistological analysis shows that at embryonic day 11 (E11), Trk-A is expressed by the epithelial cells of the presumptive pancreas. The few pancreatic endocrine cells present at that stage express Trk-A. At E12 and E16, Trk-A expression was detected in the developing ductal network. The endocrine cells located in the ducts express Trk-A while those that have migrated into the surrounding mesenchyme now stain negative for Trk-A. By E20, Trk-A expression by ductal cells has considerably decreased and can be detected only in small ducts closely associated with islet-like structures. These islet-like structures stain negative for Trk-A. After birth, insulin-positive cells arranged into islets re-express Trk-A. During the same period, NGF mRNA is found to be expressed in the developing pancreas. The expression of Trk-A and its ligand NGF in the pancreas during embryonic and fetal life suggests that NGF and its receptor could play an important role in the development of the pancreas.

Maternal mental health represents a significant global health burden. The Mercy Pregnancy and Emotional Well-being Study (MPEWS) was established to provide a comprehensive investigation of early developmental mechanisms and modifiers for maternal, fetal and child emotional well-being. MPEWS is a prospective, longitudinal study from pregnancy to 36 months postpartum that includes diagnostic measures of maternal mental health, observational measures of the mother-infant relationship, measures of child development, and repeat biological sampling. A total of 282 pregnant women were recruited in early pregnancy from the Mercy Hospital for Women in Melbourne, Australia, including 49 women on antidepressant medication, 30 non-medicated women meeting diagnostic criteria for current unipolar depression or dysthymia, and 66 women with a past history of depression. Sample recruitment characteristics included a mean age of 31 years and average gestation of 17 weeks. The MPEWS cohort was compara...

Birth weight is essential information in fetal programming studies and is generally obtained retrospectively. In Brazil's Information System on Live Births (SINASC), birth weight is valid information but is not always accessible. The study aimed to establish an algorithm for the selection of the most reliable data source for birth weight in the absence of information in the SINASC database. In a cross-sectional study of 6-14-year-old schoolchildren in Niterói, Rio de Janeiro State, Brazil, in 2010, birth weight was collected through a self-completed questionnaire, interview, medical records from the Family Physician Program, and the SINASC database. We calculated intra-class correlation coefficients (ICCs) and differences in mean birth weight. ICCs varied from 0.90 to 0.99. All the other sources showed higher mean birth weight than SINASC, allowing differences up to 100g. Birth weight is recorded at birth (SINASC) or close to it (Family Physician Program), and in the absence of ...

During the latter half of the twentieth century, an explosion of research elucidated a growing number of causes of disease and contributors to health. Biopsychosocial models that accounted for the wide range of factors influencing health began to replace outmoded and overly simplified biomedical models of disease causation. More recently, models of lifecourse health development (LCHD) have synthesized research from biological, behavioral and social science disciplines, defined health development as a dynamic process that begins before conception and continues throughout the lifespan, and paved the way for the creation of novel strategies aimed at optimization of individual and population health trajectories. As rapid advances in epigenetics and biological systems research continue to inform and refine LCHD models, our healthcare delivery system has struggled to keep pace, and the gulf between knowledge and practice has widened. This paper attempts to chart the evolution of the LCHD framework, and illustrate its potential to transform how the MCH system addresses social, psychological, biological, and genetic influences on health, eliminates health disparities, reduces chronic illness, and contains healthcare costs. The LCHD approach can serve to highlight the foundational importance of MCH, moving it from the margins of national debate to the forefront of healthcare reform efforts. The paper concludes with suggestions for innovations that could accelerate the translation of health development principles into MCH practice.

Results: The p.P286S polymorphism was identified in 17/150 patients and 12/150 controls (11.3% vs. 8.0%, p Z 0.32). The p.N589S polymorphism was identified in 22/150 patients and 12/150 controls (14.6% vs. 8.0%, p Z 0.068). The double polymorphism (S-S haplotype) was present in 16/150 patients and 6/150 controls (10.6% vs. 4.0%, p Z 0.044, OR Z 2.87, CI from 1.09 to 7.55). The association of polymorphisms consistently revealed a modification in the structure prediction or amino acid accessibility in all three in silico models. The P286S, N589S and P286S þ N589S proteins did not exhibit reduced transactivating activity on Hes3 promoter. Conclusion: Polymorphisms of MAMLD1 gene are frequent in patients with hypospadias. Although no change in transactivation was noted on Hes3 promoter, the in silico studies and the significantly increased incidence of the S-S haplotype in hypospadiac patients raise the hypothesis of a particular susceptibility conferred by these variants.

Introduction In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. Methods DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare agerelated fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA≤28 weeks for frontal cortical region and GA≤ 22 weeks for rest of the lobes. Conclusions The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports regionspecific migrational and maturational events in human fetal brain.

Background: While being small-for-gestational-age due to placental insufficiency is a major risk factor for stillbirth, 50% of stillbirths occur in appropriate-for-gestational-age (AGA, > 10th centile) fetuses. AGA fetuses are plausibly also at risk of stillbirth if placental insufficiency is present. Such fetuses may be expected to demonstrate declining growth trajectory across pregnancy, although they do not fall below the 10th centile before birth. We investigated whether reduced growth velocity in AGA fetuses is associated with antenatal, intrapartum and neonatal indicators of placental insufficiency. Methods: We performed a prospective cohort study of 308 nulliparous women who subsequently gave birth to AGA infants. Ultrasound was utilised at 28 and 36 weeks' gestation to determine estimated fetal weight (EFW) and abdominal circumference (AC). We correlated relative EFW and AC growth velocities with three clinical indicators of placental insufficiency, namely (1) fetal cerebroplacental ratio (CPR; CPR < 5th centile reflects placental resistance, and blood flow redistribution to the braina fetal response to hypoxia); (2) neonatal acidosis after the hypoxic challenge of labour (umbilical artery (UA) pH < 7.15 at birth); and (3) low neonatal body fat percentage (BF%, measured by air displacement plethysmography) reflecting reduced nutritional reserve in utero. Results: For each one centile reduction in EFW growth velocity between 28 and 36 weeks' gestation, there was a 2.4% increase in the odds of cerebral redistribution (CPR < 5th centile, odds ratio (OR) (95% confidence interval) = 1.024 (1.005-1.042), P = 0.012) and neonatal acidosis (UA pH < 7.15, OR = 1.024 (1.003-1.046), P = 0.023), and a 3.3% increase in the odds of low BF% (OR = 1.033 (1.001-1.067), P = 0.047). A decline in EFW of > 30 centiles between 28 and 36 weeks (compared to greater relative growth) was associated with cerebral redistribution (CPR < 5th centile relative risk (RR) = 2.80 (1.25-6.25), P = 0.026), and a decline of > 35 centiles was associated with neonatal acidosis ), P = 0.030). Similar associations were identified between low AC growth velocity and clinical indicators of placental insufficiency. Conclusions: Reduced growth velocity between 28 and 36 weeks' gestation among fetuses born AGA is associated with antenatal, intrapartum and neonatal indicators of placental insufficiency. These fetuses potentially represent an important unrecognised cohort at increased risk of stillbirth and may warrant more intensive antenatal surveillance.

Diabetes mellitus induction with alloxan at a dose of 110 mg/kg i.p. in rats on Day 4 of pregnancy causes delayed development and resorptions as signs of embryotoxicity. In the present study, the administration of human NPH insulin at doses of 1 to 5 U/d to rats or 1.0 mL of 10 mM L-arginine for 8 d, starting the day following diabetes induction, prevented embryotoxicity and delayed development. Similar results were obtained when the polyamines putrescine, spermidine, or spermine were administered at doses of 1.0 mL of a 10 M solution to each rat daily. However, even though L-arginine and polyamines prevented adverse effects of severe diabetes on the conceptus, and caused normalization of glucose, ␤-hydroxybutyrate levels remained elevated. These results support the hypothesis that the mechanisms of normal and altered development could be mediated by the action of polyamines.

Articles Translational Investigation nature publishing group IntroductIon: Intrauterine growth restriction (IUGR) is associated with high rates of neonatal morbidity. IUGR babies are often born preterm and are, therefore, exposed to antenatal glucocorticoids. antenatal glucocorticoids significantly improve overall survival rates of preterm infants, but there is a paucity of information about their effects on IUGR Infants. Methods: We induced IUGR in sheep by single umbilical artery ligation (sUaL), or sham in control fetuses. To half the ewes, we administered betamethasone (BM) on d 5 (BM1) and 6 (BM2) following surgery, and collected fetal lung tissue on d 7. results: sUaL alone was associated with higher circulating fetal cortisol levels (2.8 ± 0.4 vs. 1.0 ± 0.4, P = 0.001) as compared with controls but not with changes in lung morphology or surfactant protein (SP) gene expression. BM was associated with a significant reduction in lung tissue density (P = 0.048). There were no significant differences between groups in lung DNa concentration or septal crest density. SPA , SP-B, and SP-C gene expressions were significantly increased in control and sUaL fetuses that were administered BM. dIscussIon: These results show that in sUaL fetuses, maternal BM is associated with acceleration of fetal lung structure, as occurs in normally grown fetuses, and that BM induces sP production, an effect not observed in sUaL-induced IUGR fetuses alone.

We used immunohistochemical methods and four monoclonal antibodies for specific molecular structures of advanced glycation end products (AGE)-6D12, KNH-30, 1F6, and 2A2-to examine localization of AGE in fetal, young, and adult rats, and rats with streptozotocin-induced diabetes. 6D12 recognized N ⑀-(carboxymethyl)lysine (CML); KNH-30, N ⑀-(carboxyethyl)lysine (CEL); and 1F6, fluorolink. The epitope of 2A2 is as yet unknown. Immunoreactivities for these monoclonal antibodies were found in various organs and tissues in postnatal and adult rats, and accumulation increased with aging. In the fetuses, AGE structures were detected at 10 fetal days, and their accumulation increased during ontogeny. Reversed-phase high-performance liquid chromatography revealed CML in fetuses at 13 fetal days and in lungs of 28-week-old rats. In various organs and tissues of fetal, young, and adult rats, CML, CEL, 2A2-positive AGE, and fluorolink accumulated, in that order, which suggests that the accumulation of CML, a nonfluorescent/noncross-linked AGE, occurs earlier than accumulation of fluorolink, a fluorescent/cross-linked AGE. In diabetic rats, hepatocytes, splenic macrophages, renal glomerular endothelial and mesangial cells, testicular Leydig cells, and erythrocytes showed excessive accumulation of AGE, leading to the pathologic changes characteristic of diabetes mellitus. For the induction of these changes, persistent hyperglycemia and hyperketonemia might be important for acceleration of intracellular AGE accumulation in diabetic rats. Thus, AGE accumulation in tissues and cells occurs not only during aging and in diabetes mellitus but also from an early stage of ontogeny.

Non-alcoholic fatty liver disease is an urgent problem of modern medicine, affecting up to 30% of the adult population. Of particular concern is the increased incidence among pregnant women, reaching 10-15%, which is due to changes in dietary habits, decreased physical activity, increased incidence of obesity, and the age of pregnant women. Non-alcoholic fatty liver disease is associated with a number of adverse obstetric outcomes including gestational diabetes mellitus, pre-eclampsia and preterm labor. To analyze the current scientific data on the impact of nonalcoholic fatty liver disease on the course of pregnancy and perinatal outcomes. A systematic analysis of publications from 2014-2024 in Google Scholar, The Cochrane Library, Wiley Online Library, and PubMed databases was performed. The review included 6 full-text studies that met the selection criteria: randomized and cohort studies. Limited-format materials, single-case descriptions, and abstracts were excluded. According to the analyzed data, pregnant women with fatty liver disease show a higher risk of obstetric complications such as gestational diabetes mellitus, pre-eclampsia, and preterm delivery. There is also a higher incidence of fetal growth retardation, fetoplacental insufficiency, and operative delivery in women with fatty liver disease than in the general population.

for the GINI-plus Study Group ABSTRACT Background: Previous analysis in a prospective, population-based cohort reported reduced weight gain in children fed extensively hydrolyzed casein (eHF-C) formula during the first year of life but showed no effect on growth between 1 and 6 y of life. No studies have been conducted in children up to the age of 10 y. Objective: The objective was to investigate potential differences in body mass index (BMI) over the first 10 y of life between infants fed within the intervention period of the first 16 wk of life with partially hydrolyzed whey (pHF-W), extensively hydrolyzed whey (eHF-W), eHF-C, or cow-milk formula (CMF) and infants exclusively breastfed (BF) within the intervention period. Design: This was a prospective, randomized, double-blind trial in full-term neonates with atopic heredity in the German birth cohort German Infant Nutritional Intervention (GINI) followed through the first 10 y of life. Analyses of absolute and World Health Organization (WHO)-standardized BMI trajectories for 1840 infants [pHF-W (n = 253), eHF-W (n = 265), eHF-C (n = 250), CMF (n = 276), and BF (n = 796)] were conducted according to intention-to-treat principles. Results: Except for the previously reported slower BMI gain in infants fed with eHF-C formula within the first year of life, no significant differences in absolute or WHO-standardized BMI trajectories were shown between the pHF-W, eHF-W, eHF-C, CMF, and BF groups thereafter up to the age of 10 y. Conclusions: Extension of the follow-up period from 6 to 10 y for this randomized controlled trial showed no long-term consequences on BMI for the 4 infant formulas considered. These data need to be confirmed in future studies.

Experimental carcinogenesis by topical application of 7,12_dimethylbenz(a)anthracene (DMBA) in hamster buccal pouch mucosa was evaluated for expression of tenascin, an extracellular matrix glycoprotein expressed at the epithelial-mesenchymal interface during embryonic and fetal development, wound healing and in the stroma of various neoplastic lesions, by using immunohistochemical methods. The buccal pouch mucosa in normal hamsters showed immunoreactive tenascin either as a linear delicate band or without reactivity at the immediate vicinity of the basement membrane. During carcinogenesis, in the second to fourth week of application of DMBA, the hyalinous changes in the submucosal connective tissue had a weak but diffuse immunoreactivity for tenascin. The hyperkeratinised and hyperplastic mucosa following 5 weeks of application of DMBA showed focal areas of enhanced expression in the vicinity of the basement membrane. Subsequently, specimens showing hyperplasia, dysplasia, carcinoma in situ and invasive carcinomas had comparatively more widespread stromal immunoreactivity where the extent of enhanced reactivity positively correlated with the advancing lesion. These results compared with the results of expression in human normal mucosa, leukoplakia and squamous cell carcinoma of the oral cavity (Shrestha et al., Oral Oncol, Eur J Cancer 1994, 30, 132-137) suggest that the expression of tenascin in experimental carcinogenesis of hamster buccal pouch mucosa, as a model, faithfully mimics the same in human oral mucosa.

Purpose: Irrespective of the surgical technique chosen to treat high undescended testis, preservation of an adequate arterial supply for the testis is crucial for successful orchiopexy with maintenance of normal testicular size and texture. To provide an anatomical background for such a procedure, we performed a systematic study on the number and origin of arteries supplying the fetal testis during its migration from the abdomen to the scrotum. Materials and Methods: We studied bilaterally 64 testes from 32 fresh human fetuses 13 to 33 weeks after conception. The fetuses were injected through the thoracic aorta with a microvascular silicone rubber red resin to fill in the arterial tree, thereby enabling identification and dissection of all arteries supplying the testes. Results: Of the 64 testes 3 arteries (testicular, deferential and cremasteric) were found in 46 (71.9%), 2 (testicular and deferential) in 15 (23.4%) and 4 in 3 (4.7%). Conclusions: The fetal testis is always supplied by at least 2 arteries (testicular and deferential arteries) and by 3 or 4 arteries in nearly 80% of the cases.

Passive smoking (PS), a well-known health risk, is the major source of indoor pollution. There is some inconsistent evidence that PS during pregnancy may increase the risk of low birth weight. The aim of the present study was to determine the effects of PS exposure during pregnancy on weight, length and cranial circumference at birth of babies born to women who have described themselves as nonsmokers, in Kerman, Iran. A random sample of 702 admitted women aged 11 to 50 years [mean (standard deviation) 26.5 (6.1)] who delivered a live full-term singleton baby without apparent malformation during the six consecutive months from June to December 1994 were interviewed on the second day post-partum and asked about smoking in all household members. They comprised about 36.4% of total deliveries in Bahonar Kerman Medical School Hospital during this period. All women were nonsmokers, 278 (39.6%) were passive smokers while 424 (60.4%) were not exposed to tobacco smoke. Potential confounders, including fetal gender, maternal age, parity, weight gain, complications during pregnancy, maternal education, birth interval and gestation were adjusted for by multiple linear regression analysis. Infants born to passive smokers were on the average 22 gr. lighter than those born to nonsmokers, albeit this difference was not statistically significant (p = 0.56) [95% confidence interval (CI):-51, 95.7]. A mean reduction of 0.04 cm [95% CI:-0.19,0.27] in birth length and 0.05 cm [95%CI:-0.12, 0.22) in cranial circumference was found. In multiple linear regression model, exposure to PS during pregnancy did not show any effect on weight, length and cranial circumference at birth after adjusting for confounding variables.

Goal (PHG) technical support document provides information on health effects from contaminants in drinking water. PHGs are developed for chemical contaminants based on the best available toxicological data in the scientific literature. These documents and the analyses contained in them provide estimates of the levels of contaminants in drinking water that would pose no significant health risk to individuals consuming the water on a daily basis over a lifetime. The California Safe Drinking Water Act of 1996 (Health and Safety Code, Section 116365) requires the Office of Environmental Health Hazard Assessment (OEHHA) to perform risk assessments and adopt PHGs for contaminants in drinking water based exclusively on public health considerations. The Act requires that PHGs be set in accordance with the following criteria: 1. PHGs for acutely toxic substances shall be set at levels at which no known or anticipated adverse effects on health will occur, with an adequate margin of safety. 2. PHGs for carcinogens or other substances that may cause chronic disease shall be based solely on health effects and shall be set at levels that OEHHA has determined do not pose any significant risk to health. 3. To the extent the information is available, OEHHA shall consider possible synergistic effects resulting from exposure to two or more contaminants. 4. OEHHA shall consider potential adverse effects on members of subgroups that comprise a meaningful proportion of the population, including but not limited to infants, children, pregnant women, the elderly, and individuals with a history of serious illness. 5. OEHHA shall consider the contaminant exposure and body burden levels that alter physiological function or structure in a manner that may significantly increase the risk of illness. 6. OEHHA shall consider additive effects of exposure to contaminants in media other than drinking water, including food and air, and the resulting body burden. 7. In risk assessments that involve infants and children, OEHHA shall specifically assess exposure patterns, special susceptibility, multiple contaminants with toxic mechanisms in common, and the interactions of such contaminants. MOLINATE in Drinking Water California Public Health Goal (PHG) iii June 2008 8. In cases of insufficient data for OEHHA to determine a level that creates no significant risk, OEHHA shall set the PHG at a level that is protective of public health with an adequate margin of safety. 9. In cases where scientific evidence demonstrates that a safe dose response threshold for a contaminant exists, then the PHG should be set at that threshold. 10. The PHG may be set at zero if necessary to satisfy the requirements listed above in items seven and eight. 11. PHGs adopted by OEHHA shall be reviewed at least once every five years and revised as necessary based on the availability of new scientific data. PHGs adopted by OEHHA are for use by the California Department of Public Health (DPH) in establishing primary drinking water standards (State Maximum Contaminant Levels, or MCLs). Whereas PHGs are to be based solely on scientific and public health considerations without regard to economic cost considerations or technical feasibility, drinking water standards adopted by DPH are to consider economic factors and technical feasibility. Each primary drinking water standard adopted by DPH shall be set at a level that is as close as feasible to the corresponding PHG, placing emphasis on the protection of public health. PHGs established by OEHHA are not regulatory in nature and represent only non-mandatory goals. By state and federal law, MCLs established by DPH must be at least as stringent as the federal MCL, if one exists. PHG documents are used to provide technical assistance to DPH, and they are also informative reference materials for federal, state and local public health officials and the public. While the PHGs are calculated for single chemicals only, they may, if the information is available, address hazards associated with the interactions of contaminants in mixtures. Further, PHGs are derived for drinking water only and are not intended to be utilized as target levels for the contamination of other environmental media.

To investigate the possible effect of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) on somatic growth and on hormones of the hypothalamic-pituitary-adrenal (HPA) and insulin-like growth factor (IGF)-I axes, we compared the anthropometric parameters and hormonal profile of 21 SSRI-exposed infants and 20 matched controls. The SSRI group was characterized by lower crown-heel length (p Ͻ 0.01), smaller head circumference (p ϭ 0.08), and higher percentage of infants with birth weight, birth length, and head circumference below the 10th percentile (p Ͻ 0.045, p ϭ 0.08, p Ͻ 0.04, respectively), in addition to a significantly lower cord blood level of cortisol (p Ͻ 0.03) and higher level of thyroidstimulating hormone (TSH) (p Ͻ 0.004). Infants exposed to citalopram had a lower cord blood IGF-I level than infants exposed to paroxetine (p Ͻ 0.001) and controls (p Ͻ 0.003). Placental IGF-I receptor (IGF-IR) expression was significantly higher in the SSRI group than in controls (p Ͻ 0.01). Urine 5-hydroxyindoleacetic acid (5-HIAA) level was negatively correlated with birth weight (r ϭ Ϫ0.71, p Ͻ 0.025) and with dehydroepiandrosterone (DHEA) level (r ϭ Ϫ0.71, p Ͻ 0.025). The Finnegan score was correlated with dehydroepiandrosterone sulfate (DHEAS) (r ϭ 0.8, p Ͻ 0.005) and cortisol (r ϭ 0.62, p ϭ 0.05). Fetal exposure to SSRIs causes impaired intrauterine growth accompanied by alterations in the IGF-I and HPA axes. The findings may raise concern regarding maternal use of SSRIs during pregnancy.

Background: Congenital cystic adenomatoid malformation (CCAM) of the lung is an uncommon fetal development anomaly of the terminal respiratory structures. The large cyst type usually occurs in stillborn infants or newborn infants with respiratory distress. Cases of CCAM have been previously described in adulthood, more often type I with multiloculated cystic lesions. Case presentation: We report a case of type I CCAM presenting as a single, expansive cystic mass in the middle pulmonary lobe in a 38-year-old man, revealed by persistent cough and haemoptysis. Computed tomographic scan showed a single cyst with air fluid level, occupying the lateral segment of the lobe. When the type I CCAM is a single cyst, other cystic pulmonary lesions must be excluded. The intrapulmonary localization and the absence of cartilage in the cyst wall are conclusive findings of CCAM. The pathogenesis, management and differential diagnosis with other lung malformations are discussed along with a review of the literature. Conclusion: The literature data confirm that surgical resection is the treatment of choice in all cases of CCAM and in the cases of cystic pulmonary lesions with uncertain radiological findings, in order to perform a histological examination of the lesion and to prevent infection and the potential neoplastic transformation.

In the last two decades, nanotechnologies demonstrated various applications in different fields, including detection, sensing, catalysis, electronics, and biomedical sciences. However, public concerns regarding the well-being of human may hinder the wide utilization of this promising innovation. Although, humans are exposed to airborne nanosized particles from an early age, exposure to such particles has risen dramatically within the last century due to anthropogenic sources of nanoparticles. The wide application of nanomaterials in industry, consumer products, and medicine has raised concerns regarding the potential toxicity of nanoparticles in humans. In this review, the effects of nanomaterials on the reproductive system in animal models are discussed. Females are particularly more vulnerable to nanoparticle toxicity, and toxicity in this population may affect reproductivity and fetal development. Moreover, various types of nanoparticles have negative impacts on male germ cells, ...

Developing neocortical progenitors express transcription factors in gradients that induce programs of region-specific gene expression. Our previous work identified anteriorly upregulated expression gradients of a number of corticofugal neuron-associated gene probe sets along the anterior-posterior axis of the human neocortex (8-12 postconceptional weeks [PCW]). Here, we demonstrate by realtime polymerase chain reaction, in situ hybridization and immunohistochemistry that 3 such genes, ROBO1, SRGAP1, and CTIP2 are highly expressed anteriorly between 8-12 PCW, in comparison with other genes (FEZF2, SOX5) expressed by Layer V, VI, and subplate neurons. All 3 were prominently expressed by early postmitotic neurons in the subventricular zone, intermediate zone, and cortical plate (CP) from 8 to 10 PCW. Between 12 and 15 PCW expression patterns for ER81 and SATB2 (Layer V), TBR1 (Layer V/VI) and NURR1 (Layer VI) revealed Layer V forming. By 15 PCW, ROBO1 and SRGAP1 expression was confined to Layer V, whereas CTIP2 was expressed throughout the CP anteriorly. We observed ROBO1 and SRGAP1 immunoreactivity in medullary corticospinal axons from 11 PCW onward. Thus, we propose that the coexpression of these 3 markers in the anterior neocortex may mark the early location of the human motor cortex, including its corticospinal projection neurons, allowing further study of their early differentiation.

The authors examined the relation between fish consumption during pregnancy and fetal growth among 44,824 women from the Danish National Birth Cohort (1996-2002). They evaluated the associations between consumption of total fish, fatty fish, and lean fish in midpregnancy and birth weight, birth length, and head circumference among singleton full-term infants. Fish consumption was ascertained by food frequency questionnaire. The birth of infants classified below the 10th percentile for gestational age and gender was significantly increased among women who consumed more than 60 g of fish per day, as compared with women who consumed 5 g or less per day. Adjusted odds ratios were 1.24 (95% confidence interval (CI): 1.03, 1.49) for birth weight and 1.21 (95% CI: 1.01, 1.43) for head circumference. The adjusted odds ratio was borderline significant for birth length (odds ratio ¼ 1.20, 95% CI: 1.00, 1.45). These increases in risk were followed by small decreases in average values for these growth measures. Furthermore, the inverse association for total fish consumption could be explained by consumption of fatty fish, while no association was found for lean fish. These results indicate that consumption of fatty fish, a known route of exposure to persistent organic pollutants, could be associated with reduced fetal growth.

Background: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. Objective: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. Design: The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a randomand fixed-effects meta-analysis. Results: Women who ate fish .1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (#1 time/wk); the adjusted RR of fish intake .1 but ,3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake $3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for .1 but ,3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for $3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. Conclusion: This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.

Transmission of obesity across generations is of concern. Offspring of obese women have short- and long-term increased morbidities. A high intake of carbohydrate during pregnancy combined with impaired glucose tolerance is postulated to result in high birth weight, which is linked to subsequent metabolic disease. The objective was to examine the association between carbohydrate intake in obese pregnant women and their offspring&#39;s body composition. Secondary analyses were performed in an observational setting of 222 pregnant women with a pregestational BMI (in kg/m(2)) ≥30 participating in a randomized controlled trial. Diet was assessed at gestational weeks 11-14 and 36-37 by using a semiquantitative food-frequency questionnaire. Body composition in the offspring was assessed at birth by dual-energy X-ray absorptiometry. Relative fat mass (%) was the primary outcome. Absolute measures (total fat, abdominal fat, and lean body mass) were secondary outcomes. Mean ± SD weight and ab...

Determining cell identity and maturation status of differentiated pluripotent stem cells (PSCs) requires knowledge of the transcriptional and epigenetic trajectory of organs during development. Here, we generate a transcriptional and DNA methylation atlas covering 21 organs during human fetal development. Analysis of multiple isogenic organ sets shows that organ-specific DNA methylation patterns are highly dynamic between week 9 (W9) and W22 of gestation. We investigate the impact of reprogramming on organ-specific DNA methylation by generating human induced pluripotent stem cell (hiPSC) lines from six isogenic organs. All isogenic hiPSCs acquire DNA methylation patterns comparable to existing hPSCs. However, hiPSCs derived from fetal brain retain brain-specific DNA methylation marks that seem sufficient to confer higher propensity to differentiate to neural derivatives. This systematic analysis of human fetal organs during development and associated isogenic hiPSC lines provides in...

Objectives: This study was undertaken to evaluate whether prenatal zinc supplementation affects maturation of fetal cardiac patterns. Study design: A randomized double-blind controlled trial among 242 low-income Peruvian women was performed. Beginning at 10 to 16 weeks' gestation, women received supplements containing 60 mg iron, 250 mg folic acid with or without 25 mg zinc. Fetal heart rate (mean FHR, variability [HRV], number of accelerations) and movements (number and amplitude of movement bouts, time spent moving) were electronically monitored monthly from 20 weeks' gestation. Developmental trends were evaluated by supplement type among 195 women who completed the trial and had no serious complications of pregnancy. Results: Zinc supplementation was associated with lower FHR, greater number of accelerations, and greater HRV. Supplementation effects on HRV and accelerations were more pronounced after 28 weeks' gestation. No differences in motor activity were observed. Conclusion: Prenatal supplementation of zinc-deficient mothers may be beneficial to fetal neurobehavioral development.