Vitamin D supplementation during pregnancy to prevent vitamin D deficiency in newborns: a systematic review and meta-analysis / Suplementação de vitamina D durante a gravidez para a prevenção da deficiência de vitamina D em recém-nascidos: uma revisão sistemática e meta-análise

Abstract Objectives: to assess the effects of vitamin D supplementation during pregnancy on the outcomes of vitamin D concentration in newborns, length at birth, overall health (Apgar), birth weight and maternal vitamin D concentration after childbirth. Methods: this research was conducted in the electronic databases of MEDLINE, LILACS, EMBASE and Cochrane Library until December 2020, using the terms "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" and their synonyms. Randomized controlled trials were searched by evaluating the effects of maternal vitamin D supplementation in neonates. The data was analyzed on RevMan 5.4 software and the quality of evidence on GRADE. Results: the newborn's overall health condition was presented as Apgar, with a mean difference (MD) of 0.15 (CI95%=0.06-0.25; p=0.002; I2=0%, two studies, 648 participants, moderate quality evidence) at the first minute and 0.11 (CI95%=0.04-0.17; p=0.001; I2=0%, two studies, 648 participants, moderate quality evidence) at the fifth minute. Significant effects were also presented at the length at birth considering any supplemented dose (MD=0.19; CI95%=0.08-0.30; p=0.0010; I2=0%, 1452 participants, low quality evidence) and birth weight in doses higher than 4000IU/day (MD=257.05 (CI95%=137.81-376.29; p<0.0001; I2=14%, 176 participants, moderate quality evidence). Conclusion: vitamin D supplementation during pregnancy improves serum 25 (OH) D concentration and suggests positive effects on overall health condition, length at birth and birth weight. PROSPERO CRD42017073292.

Resumo Objetivos: avaliar os efeitos da suplementação materna de vitamina D durante a gravidez nos desfechos concentração de vitamina D no recém-nascido, comprimento ao nascer, estado geral de saúde (Apgar), peso ao nascer e concentração de vitamina D materna após o nascimento. Métodos: a pesquisa foi conduzida nas bases de dados eletrônicas MEDLINE, LILACS, EMBASE e Cochrane Library até dezembro de 2020, utilizando os termos "vitamin D", "pregnancy", "vitamin D deficiency", "infant", "newborn" e seus sinônimos. Pesquisou-se por ensaios clínicos randomizados avaliando os efeitos da suplementação materna de vitamina D no neonato. Os dados foram analisados pelo software RevMan 5.4 e a avaliação da qualidade das evidências pelo GRADE. Resultados: o estado geral de saúde do recém-nascido foi apresentado como Apgar, com uma diferença de média (DM) de 0,15 (IC95%=0,06-0,25; p=0,002; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para o teste no primeiro minuto e 0,11 (IC95%=0,04-0,17; p=0,001; I2=0%, dois estudos, 648 participantes, evidência de qualidade moderada) para quinto minuto. Efeitos significativos também foram apresentados para o comprimento ao nascer em qualquer dose suplementada (DM=0,19 (IC95%=0,08-0,30; p=0,0010; I2=0%, 1452 participantes, evidência de baixa qualidade) e peso ao nascer em doses maiores que 4000UI/dia (DM=257,05 (IC95%=137,81-376,29; p<0,0001; I2=14%, 176 participantes, evidência de qualidade moderada). Conclusão: a suplementação de vitamina D durante a gravidez melhora a concentração sérica de 25 (OH)D e sugere apresentar efeitos positivos no estado geral de saúde, comprimento ao nascer e peso ao nascer. PROSPERO CRD42017073292.

Association of prenatal sex steroid exposure estimated by the digit ratio (2D:4D) with birth weight, BMI and muscle strength in 6- to 13-year-old Polish children.

OBJECTIVES: The aim of this paper was to provide evidence for the impact of prenatal sex steroid exposure on prenatal and postnatal body size parameters, and muscle strength in children. METHODS: The following anthropometric data were studied in a group of 1148 children (536 boys and 612 girls) aged 6-13 years: the 2D:4D digit ratio, birth weight and length, and birth head and chest circumference. Postnatal parameters (6-13 years) included body weight and height, BMI, waist and hip circumference, WHR, as well as grip strength in both hands. All parameters that required it were adjusted for sex and gestational or chronological age. A general linear model, Pearson's correlation, t-statistics and Cohen's Δ were used in statistical analysis. RESULTS: Among birth size parameters, only birth weight was significantly negatively correlated with the 2D:4D digit ratio in children. Higher (feminized) digit ratios were significantly correlated with postnatal parameters such as body weight, BMI, and waist and hip circumference (positively), as well as hand grip strength-a proxy for muscular strength (negatively). CONCLUSION: Problems with maintaining adequate body size parameters and muscle strength may be programmed in fetal life and predicted on the basis of the 2D:4D digit ratio. Body weight at birth and in early ontogenesis are additive correlates of the 2D:4D ratio. The present findings suggest that the 2D:4D digit ratio is related to postnatal phenotypes such as birth weight, overweight, and obesity as well as muscle strength in 6-13-year-old children of both sexes.

Choline acts during preimplantation development of the bovine embryo to program postnatal growth and alter muscle DNA methylation.

The preimplantation period of embryonic development can be a key window for programming of postnatal development because extensive epigenetic remodeling occurs during this time. It was hypothesized that modification of one-carbon metabolism of the bovine embryo by addition of the methyl-donor choline to culture medium would change postnatal phenotype through epigenetic modification. Embryos produced in vitro were cultured with 1.8 mM choline chloride or control medium. Blastocysts were transferred into females and pregnancy outcomes and postnatal phenotype of the resultant calves determined. Exposure of embryos to choline increased gestation length and calf birth weight. Calves derived from choline-treated embryos were also heavier at weaning and had increased ratio of body weight to hip height than control calves. Choline altered muscle DNA methylation of calves 4 months after birth. A total of 670 of the 8149 CpG examined were differentially methylated, with the predominant effect of choline being hypomethylation. Among the genes associated with differentially methylated CpG were ribosomal RNAs and genes in AMPK, mTOR, integrin, and BEX2 canonical pathways and cellular functions involved in growth and proliferation. Results demonstrate that provision of the methyl-donor choline to the preimplantation embryo can alter its developmental program to increase gestation length, birth weight, and weaning weight and cause postnatal changes in muscle DNA methylation including those associated with genes related to anabolic processes and cellular growth. The importance of the nutritional status of the embryo with respect to one-carbon metabolism for ensuring health and well-being after birth is emphasized by these observations.

Wellbeing, quality of life, presence of concurrent diseases, and survival times in untreated and treated German Shepherd dogs with dwarfism.

BACKGROUND: Pituitary dwarfism (PD) in German Shepherd dogs (GSD) is a rare endocrinopathy. Cause and inheritance of the disease are well characterized, but the overall survival time, presence of concurrent diseases, quality of life (QoL) and influence of different treatment options on those parameters is still not well investigated. The aim of this study was to obtain data regarding the disease pattern of GSD with PD and to investigate the impact of treatment. METHODS: 47 dogs with dwarfism (presumably PD) and 94 unaffected GSD serving as controls were enrolled. Data were collected via a standardized questionnaire, which every owner of a participating dog had completed. Dogs with PD were grouped based on three categories of treatment: Group 1 (untreated), group 2 (treated with levothyroxine), group 3 (treated with thyroxine and progestogens or with growth hormone (GH)). Groups were compared using One-Way-Anova, Kruskal-Wallis test or Wilcoxon-rank-sum test. Categorical analysis was performed using Two-Sample-Chi-Squared-test. RESULTS: Dogs treated with thyroxine and gestagen or GH were significantly taller and heavier compared to all other dogs with PD. Quality of life was best in dogs with PD treated with thyroxine and similar to unaffected GSD. Treatment increased survival time in dogs with PD independent of the treatment strategy. Dogs receiving thyroxine and progestogens or GH did not develop chronic kidney disease (CKD). CONCLUSION: GSD with PD should be treated at least for their secondary hypothyroidism to increase survival time. Additional treatment with progestogens or GH improves body size and seems to protect against the occurrence of CKD.

Effects of Diethylstilbestrol on Zebrafish Gonad Development and Endocrine Disruption Mechanism.

Environmental estrogen is a substance that functions as an endocrine hormone in organisms and can cause endocrine system disruption. A typical environmental estrogen, diethylstilbestrol (DES), can affect normal sexual function and organism development. However, even though the effects of different exposure stages of DES on the endocrine system and gonadal development of zebrafish juveniles are unknown, sex determination is strongly influenced by endocrine-disrupting chemicals (EDCs). From 10-90 days post fertilization (dpf), juvenile zebrafish were exposed to DES (100 and 1000 ng/L) in three different stages (initial development stage (IDS), 10-25 dpf; gonadal differentiation stage (GDS), 25-45 dpf and gonadal maturity stage (GMS), 45-60 dpf). Compared with that of IDS and GMS, the growth indicators (body length, body weight, and others) decreased significantly at GDS, and the proportion of zebrafish females exposed to 100 ng/L DES was significantly higher (by 59.65%) than that of the control; in addition, the zebrafish were biased towards female differentiation. The GDS is a critical period for sex differentiation. Our results show that exposure to environmental estrogen during the critical gonadal differentiation period not only affects the development of zebrafish, but also affects the population development.

The effect of postnatal corticosteroids on growth parameters in infants with bronchopulmonary dysplasia.

OBJECTIVES: Corticosteroids are administered to ventilator dependent infants with bronchopulmonary dysplasia (BPD) to improve respiratory function and facilitating extubation. Acutely, however, growth impairment can occur as a side effect of such therapy. We aimed to determine the effect of corticosteroids on postnatal growth during the entire neonatal intensive care unit (NICU) admission. METHODS: A whole population study of extremely preterm infants with BPD was undertaken. Corticosteroid therapy was classified as treatment with dexamethasone or hydrocortisone for a least five consecutive days. Growth was calculated as the difference in weight and head circumference z-score from birth to discharge. RESULTS: Six thousand, one hundred and four infants with BPD were included of whom 28.3% received postnatal corticosteroids. Infants receiving corticosteroids were less mature (GA 25.0 vs. 26.3 weeks) and of lower birthweight (0.70 vs. 0.84 kg) than those not receiving treatment. There were no significant differences between those who did and did not receive corticosteroids in weight gain (p=0.61) or head circumference growth (p=0.33) from birth to discharge. Single vs. multiple courses of postnatal corticosteroids did not result in significant differences in weight (p=0.62) or head circumference (p=0.13) growth. CONCLUSIONS: Postnatal corticosteroid treatment did not affect the longer term growth of preterm infants with BPD.

A retrospective analysis of growth hormone therapy in children with Schaaf-Yang syndrome.

Short stature is a common phenotype in children with Schaaf-Yang syndrome (SYS). Prader-Willi syndrome (PWS) and SYS share several phenotypic features including short stature, muscular hypotonia and developmental delay/intellectual disability. Evidence exists that similar to PWS, growth hormone (GH) deficiency may also be a feature of SYS. Recombinant human GH (rhGH) therapy has been approved for PWS, but the effects of rhGH therapy in individuals with SYS have not yet been documented. This retrospective, questionnaire-based study analyzes the prevalence of rhGH therapy in children with SYS, the effects of rhGH therapy on anthropometric measures, and parental perception of the treatment. Twenty-six individuals with SYS were sent a clinical questionnaire and a request for growth charts. We found a significant increase in height z-score (p* = 0.04) as well as a significant decrease in body mass index 6 months after rhGH therapy initiation (p* = 0.04). Furthermore, height z-scores of the treated group (mean z-score = -1.00) were significantly higher than those of the untreated group (mean z-score = -3.36, p = 0.01) at time of enrollment. All parents reported an increase in muscle strength and endurance, and several families noted beneficial effects such as improved cognition and motor development.

Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women's health across the nation 1999-2018.

BACKGROUND/OBJECTIVES: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women. SUBJECTS/METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women's Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS: After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA. CONCLUSIONS: Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.

Improvement of water quality for mass anopheline rearing: evaluation of the impact of ammonia-capturing zeolite on larval development and adult phenotypic quality.

BACKGROUND: Malaria vector control approaches that rely on mosquito releases such as the sterile insect technique (SIT) and suppression or replacement strategies relying on genetically modified mosquitoes (GMM) depend on effective mass production of Anopheles mosquitoes. Anophelines typically require relatively clean larval rearing water, and water management techniques that minimise toxic ammonia are key to achieving optimal rearing conditions in small and large rearing facilities. Zeolites are extensively used in closed-system fish aquaculture to improve water quality and reduce water consumption, thanks to their selective adsorption of ammonia and toxic heavy metals. The many advantages of zeolites include low cost, abundance in many parts of the world and environmental friendliness. However, so far, their potential benefit for mosquito rearing has not been evaluated. METHODS: This study evaluated the independent effects of zeolite and daily water changes (to simulate a continuous flow system) on the rearing of An. coluzzii under two feed regimes (powder and slurry feed) and larval densities (200 and 400 larvae per tray). The duration of larval development, adult emergence success and phenotypic quality (body size) were recorded to assess the impact of water treatments on mosquito numbers, phenotypic quality and identification of optimal feeding regimes and larval density for the use of zeolite. RESULTS: Overall, mosquito emergence, duration of development and adult phenotypic quality were significantly better in treatments with daily water changes. In treatments without daily water changes, zeolite significantly improved water quality at the lower larval rearing density, resulting in higher mosquito emergence and shorter development time. At the lower larval rearing density, the adult phenotypic quality did not significantly differ between zeolite treatment without water changes and those with daily changes. CONCLUSIONS: These results suggest that treating rearing water with zeolite can improve mosquito production in smaller facilities. Zeolite could also offer cost-effective and environmentally friendly solutions for water recycling management systems in larger production facilities. Further studies are needed to optimise and assess the costs and benefits of such applications to Anopheles gambiae (s.l.) mosquito-rearing programmes.

Effects of prenatal exposure factors on birth outcomes through mediation of favorable fetal growth conditions using structural equation modeling.

BACKGROUND: Birth weight, birth length, and gestational age are major indicators of newborn health. Several prenatal exposure factors influence the fetal environment. The aim of the study was to investigate the effect of prenatal exposure factors, including socio-demographic, behavioural, dietary, physical activity, clinical and environmental on birth outcomes through the mediation of Favourable Fetal Growth Conditions (FFGC). METHODS: Data was obtained from six hundred and fifty-six Mother and Child in the Environment birth cohort study in Durban, South Africa from 2013 to 2017. We adopted structural equation models which evaluate the direct and indirect effects by allowing multiple simultaneous equations to incorporate confounding and mediation. RESULTS: A significant direct and indirect effect of FFGC on newborn weight, length, and gestational age was seen. Gestational weight gain and maternal body mass index in the first trimester exerted a mediation effect between maternal behavioural risk factors and FFGC. Similarly, the level of physical activity during pregnancy was associated with decreased gestational weight gain. The effects of maternal characteristics on newborn weight, length, and gestational age were largely indirect, operating through FFGC as a latent variable. CONCLUSIONS: Gestational weight gain and maternal pre-gestational BMI were observed to mediate the association between prenatal behavioural risk factors and favourable fetal growth conditions. TRIAL REGISTRATION: Retrospectively registered from 01 March 2013.

Methylglyoxal influences development of Caenorhabditis elegans via lin-41-dependent pathway.

Methylglyoxal is a highly reactive dicarbonyl compound. It can be obtained either endogenously through biological enzymatic/non-enzymatic pathways or exogenously via the uptake of certain foods and beverages, such as Manuka honey. Studies about its biological properties are quite controversial, though the majority reported a positive association between methylglyoxal and certain pathologies. In this report, we tested if methylglyoxal can alter the development of animals using Caenorhabditis elegans as the in vivo model. Treatment of methylglyoxal at 0.1 and 1 mmol/L for 2 days significantly inhibited the development of Caenorhabditis elegans, particularly targeting the transition from L3 stage. Pharyngeal pumping rate, the food intake marker was also significantly reduced by methylglyoxal at both 0.1 and 1 mmol/L. Additionally, treatment of 0.1 mmol/L methylglyoxal increased, while 1 mmol/L methylglyoxal decreased the nematodes' average moving speed. The effect of methylglyoxal on development was in part due to the modulation of lin-41, which encodes a homolog of human TRIM71. The mutation of lin-41 could alleviate or abolish the effects of methylglyoxal on growth rate, body size, pumping rate and locomotive activity. In summary, these results suggested that methylglyoxal influenced the development of Caenorhabditis elegans, which is in part via the lin-41-dependent pathway.

Daily supplementation with the Lab4P probiotic consortium induces significant weight loss in overweight adults.

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45-65 years with BMI 25-29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p < 0.0001) was detected favouring the probiotic group. Supplementation also resulted in significant between group decreases in waist circumference (2.58 cm, 95% CI 3.23, 1.94, p < 0.0001) and hip circumference (2.66 cm, 95% CI 3.28, 2.05, p < 0.0001) but no changes in blood pressure were observed. These findings support the outcomes of a previous shorter-term Lab4P intervention study in overweight and obese participants (PROMAGEN, ISRCTN12562026). We conclude that Lab4P has consistent weight modulation capability in free-living overweight adults.

The Effects of Vitamin D Supplementation During Infancy on Growth During the First 2 Years of Life.

CONTEXT: The relationship between maternal and infant vitamin D and early childhood growth remains inadequately understood. OBJECTIVE: This work aimed to investigate how maternal and child 25-hydroxyvitamin D (25[OH]D) and vitamin D supplementation affect growth during the first 2 years of life. METHODS: A randomized, double-blinded, single-center intervention study was conducted from pregnancy until offspring age 2 years. Altogether 812 term-born children with complete data were recruited at a maternity hospital. Children received daily vitamin D3 supplementation of 10 µg (group 10) or 30 µg (group 30) from age 2 weeks to 2 years. Anthropometry and growth rate were measured at age 1 and 2 years. RESULTS: Toddlers born to mothers with pregnancy 25(OH)D greater than 125 nmol/L were at 2 years lighter and thinner than the reference group with 25(OH)D of 50 to 74.9 nmol/L (P < .010). Mean 2-year 25(OH)D concentrations were 87 nmol/L in group 10 and 118 nmol/L in group 30 (P < .001). When group 30 was compared with group 10, difference in body size was not statistically significant (P > .053), but group 30 had slower growth in length and head circumference between 6 months and 1 year (P < .047), and more rapid growth in weight and length-adjusted weight between 1 and 2 years (P < .043). Toddlers in the highest quartile of 25(OH)D (> 121 nmol/L) were shorter (mean difference 0.2 SD score [SDS], P = .021), lighter (mean difference 0.4 SDS, P = .001), and thinner (in length-adjusted weight) (mean difference 0.4 SDS, P = .003) compared with the lowest quartile (< 81.2 nmol/L). CONCLUSION: Vitamin D and early childhood growth may have an inverse U-shaped relationship.

Nitrate and nitrite exposure leads to mild anxiogenic-like behavior and alters brain metabolomic profile in zebrafish.

Dietary nitrate lowers blood pressure and improves athletic performance in humans, yet data supporting observations that it may increase cerebral blood flow and improve cognitive performance are mixed. We tested the hypothesis that nitrate and nitrite treatment would improve indicators of learning and cognitive performance in a zebrafish (Danio rerio) model. We utilized targeted and untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to examine the extent to which treatment resulted in changes in nitrate or nitrite concentrations in the brain and altered the brain metabolome. Fish were exposed to sodium nitrate (606.9 mg/L), sodium nitrite (19.5 mg/L), or control water for 2-4 weeks and free swim, startle response, and shuttle box assays were performed. Nitrate and nitrite treatment did not change fish weight, length, predator avoidance, or distance and velocity traveled in an unstressed environment. Nitrate- and nitrite-treated fish initially experienced more negative reinforcement and increased time to decision in the shuttle box assay, which is consistent with a decrease in associative learning or executive function however, over multiple trials, all treatment groups demonstrated behaviors associated with learning. Nitrate and nitrite treatment was associated with mild anxiogenic-like behavior but did not alter epinephrine, norepinephrine or dopamine levels. Targeted metabolomics analysis revealed no significant increase in brain nitrate or nitrite concentrations with treatment. Untargeted metabolomics analysis found 47 metabolites whose abundance was significantly altered in the brain with nitrate and nitrite treatment. Overall, the depletion in brain metabolites is plausibly associated with the regulation of neuronal activity including statistically significant reductions in the inhibitory neurotransmitter γ-aminobutyric acid (GABA; 18-19%), and its precursor, glutamine (17-22%). Nitrate treatment caused significant depletion in the brain concentration of fatty acids including linoleic acid (LA) by 50% and arachidonic acid (ARA) by 80%; nitrite treatment caused depletion of LA by ~90% and ARA by 60%, change which could alter the function of dopaminergic neurons and affect behavior. Nitrate and nitrite treatment did not adversely affect multiple parameters of zebrafish health. It is plausible that indirect NO-mediated mechanisms may be responsible for the nitrate and nitrite-mediated effects on the brain metabolome and behavior in zebrafish.

Growth and Bone Mineral Density Changes in Ovariectomized Rats Treated with Estrogen Receptor Alpha or Beta Agonists.

BACKGROUND: Estrogen controls the pubertal growth spurt, growth plate closure, and accretion of bone mineral density (BMD) of long bones after biding estrogen receptor (ER). There are two subtypes of ER, ERα and ERß. If each ER subtype has different effects, we may control those actions by manipulating the estrogen binding intensity to each ER subtype and increase the final adult height without markedly reducing BMD or impairing reproductive functions. The purpose of our study was to compare these effects of ERα and ERß on long bones in ovariectomized rats. METHODS: Thirty female rats were ovariectomized and randomly divided into 3 groups. The control, propylpyrazole triol (PPT), and 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) groups were subcutaneously injected for 5 weeks with sesame oil, PPT as an ERα agonist, and DPN as an ERß agonist, respectively. The crown-lump length and body weight were measured weekly. BMD, serum levels of growth hormone (GH) and estradiol were checked before and after 5 weeks of injections. Pituitary GH1 expression levels were determined with quantitative real-time polymerase chain reaction, the proximal tibias were dissected, decalcified and stained with hematoxylin-eosin, and the thicknesses of epiphyseal plates including proliferative and hypertrophic zones were measured in 20-evenly divided sites after 5 weeks of injections. Comparisons for auxological data, serum hormone and pituitary GH1 expression levels, BMD, and epiphyseal plate thicknesses among 3 groups before and after injections were conducted. RESULTS: There was no significant difference in body lengths among 3 groups. The body weights were significantly lower, but, serum GH, pituitary GH1 expression levels, and BMDs were higher in PPT group than the other 2 groups after 5 weeks of injections. There was no significant difference in the thicknesses of the total epiphyseal plate, proliferative, and hypertrophic zone among 3 groups. CONCLUSION: ERα is more involved in pituitary GH secretion and bone mineral deposition than ERß. Weight gain might be prevented with the ERα agonist.

Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother-Infant Pairs from Shanghai.

Phthalates are hormonally active pollutants. In-utero exposure to phthalates has been reported to be associated with birth size parameters and pregnancy outcomes. However, previous reports were inconsistent. We examined the associations between meconium exposure to phthalates and the effects on birth size parameters, pregnancy outcomes and sex and thyroid hormones in 251 mother-infant pairs from a Shanghai hospital. We measured 10 metabolites of phthalates in meconium samples collected during the first 24h after delivery. Information on seven birth size parameters (birth weight, birth length, abdominal circumference, head circumference, femur length, biparietal diameter and anogenital distance) and three pregnancy outcomes (gestational diabetes, premature rupture of membrane, and premature birth) was available from the birth record. Concentrations of free testosterone, estradiol (E2), thyroid stimulating hormone, concentrations of total and free thyroxine and triiodothyronine were measured from cord blood. Multivariate linear regression and logistic regression were used to estimate associations between phthalate exposure and health outcomes. mono-iso-butylphthalate (MiBP), mono-n-butylphthalate (MnBP) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) were positively associated with birth length and femur length which seemed more obvious in female newborn; MiBP, MnBP and mono-2-ethylhexylphthalate (MEHP) were positively associated with gestational diabetes mellitus (GDM) only in mothers with male newborns; monomethyl phthalate (MMP), MiBP and MEOHP were positively associated with E2 in male newborns. This study indicates that meconium exposure to phthalates may adversely affect some fetal growth parameters and GDM with a potential gender effect.

Serotonin signaling suppresses the nutrition-responsive induction of an alternate male morph in horn polyphenic beetles.

Environment-responsive development contributes significantly to the phenotypic variation visible to selection and as such possesses the potential to shape evolutionary trajectories. However, evaluation of the contributions of developmental plasticity to evolutionary diversification necessitates an understanding of the developmental mechanisms underpinning plastic trait expression. We investigated the role of serotonin signaling in the regulation and evolution of horn polyphenism in the beetle genus Onthophagus. Specifically, we assessed the role of serotonin in development by determining whether manipulating serotonin biosynthesis during the larval stage alters body size, developmental rate, and the formation of relative adult trait size in traits characterized by minimal (genitalia), moderate (elytra), and pronounced (horns) nutrition-responsive development in O. taurus. Second, we assessed serotonin's role in evolution by replicating a subset of our approaches across four species reflecting ancestral as well as derived conditions. Lastly, we employed immunohistochemical approaches to begin assessing whether serotonin may be acting via the endocrine or nervous system. Our results show that pharmacological manipulation of serotonin signaling affects overall size, developmental rate, and the body size threshold separating alternate male morphs. Threshold body sizes were affected across species, regardless of the severity of horn polyphenism, and independent of the precise morphological location of horns. However, histological assessments suggest it is unlikely serotonin functions as a neurotransmitter and instead may rely on other mechanisms that remain to be identified. We discuss the most important implications of our results for our understanding of the evolution of and through plasticity in horned beetles and beyond.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.

BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (ß = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (ß = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (ß = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (ß = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (ß = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (ß = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (ß = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (ß = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Genetic Variation Influences Tolerance to a Neonicotinoid Insecticide in 3 Butterfly Species.

Neonicotinoid pesticides harm nontarget insects, but their sublethal effects on butterflies are understudied. We exposed larvae of 3 butterfly species (Pieris rapae, Colias philodice, and Danaus plexippus) to low levels of the neonicotinoid imidacloprid in their host plants and followed individuals to adulthood. Imidacloprid altered adult body size, especially in female monarchs, but its effects varied across maternal families, highlighting the importance of considering genetic variation in ecotoxicological testing. Environ Toxicol Chem 2020;39:2228-2236. © 2020 SETAC.

Transcriptome sequencing reveals the effects of cadmium toxicity on the cold tolerance of the wolf spider Pirata subpiraticus.

As the predominant predator of pests in rice fields, spiders have been exposed to cadmium (Cd) pollution for a long time. The livability of spiders during the overwintering period is closely related to population growth in spring, but the effects of Cd on spider's survival of cold hardness and the underlining mechanism remain unclear. In the present study, we found that some growth parameters (body length, width, mass and livability) in the wolf spider Pirata subpiraticus were altered distinctively under Cd stress. To investigate the effects of Cd toxicity on the spider at molecular levels, RNA-sequencing was performed on the spiderlings undergoing ambient temperature alterations. Transcriptome data showed that a total of 807 differentially expressed genes (DEGs) were yielded in the comparison. The obtained DEGs were mainly linked with metabolism-related process, including oxidoreductase activity and lipid transport, and 25 DEGs were associated with the reported cryoprotectants, including glycerol, arginine, cysteine, heat shock protein, glucose and mannose. Growth factors (insulin growth factor, platelet-derived growth factor and transforming growth factor) and cytochrome P450 encoding genes were dramatically expressed in the spider. Furthermore, transcriptional factors (TFs) family were characterized according to the transcriptomic profile, and ZBTB TFs were represented the most distinctive alterations in the characterized genes. Collectively, our study illustrated that Cd poses disadvantageous effects on the growth of P. subpiraticus at cold ambient temperature, and the spiders are capable of responding to the adverse Cd stress by expressing the genes involved in the metabolism of energy substances, cryoprotectants and immune-related components.