Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Genetic effect of season on the preweaning growth of beef cattle: A first approach on Retinta calves / Efecto genético de la estación climática sobre el crecimiento predestete del ganado de carne: Un primer estudio en terneros de raza Retinta / Efeito genético de estações climáticas no crescimento pré-desmame de bovinos de corte: uma primeira abordagem para os bezerros Retinta

Abstract Background: Heat stress derived from global warming is causing major economic losses in the livestock industry. Objective: To develop a novel methodological approach for determining the influence of climatic factors on the estimation of genetic parameters for growth traits in Retinta cattle breed by using reaction-norm models. Methods: Live weight records (n=7,753) from 3,162 Retinta calves born from 1,249 dams and 85 sires and raised in the Andalusian region (Spain) were analyzed. The effect of heat stress was measured using the temperature-humidity index, calculated with climatological data obtained from four weather stations. A bivariate-random-regression reaction-norm model was used to estimate the (co)variance components of weight until weaning in two different climatic seasons corresponding to warm and cold months. Results: The heritability pattern of individuals reared under diverse environments during the first 90 days of age was different. However, differences were not significant at the end of the growing period. Weaned calves reared during the cold season showed greater growth from 70 to 160 days in comparison with those reared during the warm season. Conclusions: Overall, this assessment did not show significant effects of the genotype-environment interaction. However, highly significant evidence of genotype-climatic condition interaction was found during the calf´s first three months of age.

Resumen Antecedentes: El estrés térmico derivado del calentamiento global está causando pérdidas económicas en la industria ganadera. Objetivo: Desarrollar un enfoque metodológico para estimar la influencia de algunos factores climáticos sobre la estimación de parámetros genéticos en las variables de crecimiento de la raza bovina Retinta. Métodos: Se analizaron registros de peso vivo (n=7.753) de 3.162 terneros hijos de 1.249 vacas y 85 toros, criados en la región de Andalucía (España). El efecto del estrés térmico se midió mediante un índice de temperatura-humedad obtenido a partir de los datos de cuatro estaciones meteorológicas. Se usó un modelo bivariado de regresión aleatoria de "norma-reacción" para estimar la (co)varianza del peso hasta el destete en dos diferentes épocas climáticas correspondientes a los meses cálidos y fríos. Resultados: Se encontraron diferencias en el patrón de heredabilidad de individuos criados en diferentes ambientes durante los primeros 90 días de vida. Sin embargo, tales diferencias no fueron significativas al final del periodo de crecimiento. Los terneros destetados en la época fría mostraron un mayor crecimiento entre 70 y 160 días en comparación con los criados en la temporada cálida. Conclusiones: Se encontró una evidencia altamente significativa de la interacción genotipo-condición climática durante los primeros tres meses de crecimiento del ternero.

Resumo Antecedentes: O estresse térmico devido ao aumento da temperatura média está produzindo grandes perdas econômicas na indústria pecuária. Objetivo: Realizar uma nova abordagem metodológica para estimar a importância dos fatores climáticos em parâmetros genéticos em variáveis de crescimento da população da raça Retinta. Métodos: Foram analisados registros de peso vivo (n=7.753) de 3.162 Retinta bezerros, nascidos de 1.249 vacas e 85 touros criados na região da Andaluzia (Espanha). O efeito do estresse térmico foi medido utilizando o índice de temperatura-umidade obtido com dados climatológicos de quatro estações meteorológicas. Um modelo de regressão aleatória bivariado de norma-reação foi usado para estimar os componentes da (co)variância do peso à desmama em duas estações climáticas com correspondência aos meses quentes e fríos. Resultados: Diferenças foram encontradas no padrão de herdabilidade de indivíduos criados em diferentes ambientes nos primeiros 90 dias de idade. No entanto, essas diferenças não foram significativas no final do período de crescimento. Os bezerros desmamados globalmente na estação fria apresentaram um crescimento maior dos 70 aos 160 dias em comparação com os indivíduos criados na estação quente. Conclusões: Uma evidência altamente significativa da interação genótipo-ambiente foi encontrada durante os primeiros três meses de crescimento do bezerro.

Inbreeding depression and average genetic components in green corn genotypes / Depressão por endogamia e componentes genéticos de média em genótipos de milho verde

ABSTRACT: This study aimed to evaluate the inbreeding depression and average genetic components in seven hybrids and two open pollinated cultivars for green corn production, as well as to select the best genotypes in order to obtain base populations for inbred lines extraction. The experiment was carried out in a randomized complete block design with four replications, in a split plot design, with inbreeding levels arranged in the plots and the different genotypes distributed over the subplots, in the municipality of Sabáudia - PR, during the 2014/15 crop season. Higher values of dominance and inbreeding depression were observed for yield of both unhusked and commercial ears. Higher additive effects were detected on length and diameter of commercial ears. The genotypes AM811, Cativerde 02 and AG4051 showed greater probability of obtaining highly productive and higher quality green corn inbred lines.

RESUMO: O trabalho teve por objetivo avaliar a depressão por endogamia e os componentes genéticos de médias em sete híbridos e em duas variedades de polinização aberta para uso como milho verde, para seleção de genótipos visando à formação de populações-base para a extração de linhagens. Para a realização do estudo, foi instalado um experimento no município de Sabáudia - PR, no ano agrícola de 2014/15. O experimento foi delineado em blocos completos ao acaso, com quatro repetições, em arranjo de parcelas subdivididas, com as gerações de endogamia e os diferentes genótipos ocupando as parcelas e as subparcelas, respectivamente. As maiores estimativas de dominância e de depressão endogâmica foram observadas na produtividade de espigas empalhadas e comerciais. Os efeitos aditivos foram mais expressivos na herança do comprimento e do diâmetro de espigas comerciais. Os genótipos AM811, Cativerde 02 e AG4051 apresentaram maiores probabilidades no sucesso de extração de linhagens destinadas à produtividade e qualidade de milho verde.

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles"

PURPOSE: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. METHODS: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. RESULTS: The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. CONCLUSION: Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles"

PURPOSE: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. METHODS: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. RESULTS: The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. CONCLUSION: Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.

Screening of herbal extracts influencing hematopoiesis and their chemical genetic effects in embryonic zebrafish

Objective: To screen the herbal extracts influencing the hematopoietic stem cells (HSC) in zebrafish embryos and their chemical genetic effects. Methods: The herbals used in this study had been widely applicable in Siddha medicines in South India. Herbal extracts were treated in zebrafish embryos at 4 d post fertilization and the extracts inducing the HSC were enumerated in hemocytometer. The biocompatibility and the organogenesis of the screened extracts were assessed in the zebrafish embryos for their chemical genetic effects. The LC50 values were calculated with their parallel control. The blood cells were enumerated. Results: The level of RBC was found increased in the Bergera koenigii (B. koenigii) at 15 μg/mL (P<0.05), Mimosa pudica (M. pudica) at 20 μg/mL (P<0.05) and Solanum trilobatum (S. trilobatum) at 25 μg/mL (P<0.05) and decreased RBC level was found in Phyllanthus niruri (P. niruri) at 30 μg/mL (P<0.05). The WBC count was found increased in S. trilobatum at 20 μg/mL (P<0.05) and Annona muricata (Annona muricata) at 15 μg/mL (P<0.05) and the Vitis quadrangularis (V. quadrangularis) at 20 μg/mL (P<0.05) decreased the WBC level. There were no notable effects in heart beats and the chemical genetic effects were observed at higher concentration of the extract resulting in Pericardial bulging, trunk tail flexure with heart edema, fin fold deformities etc. Conclusions: This in vivo based screening of Hematopoiesis is an inexpensive assay to screen herbal compounds and found that S. trilobatum extract influenced embryonic HSC in zebrafish, which could be a therapeutic for blood related disorders.

Inclusão da epistasia em modelo de avaliação genética de bovinos de corte compostos / The effect of the inclusion of epistasis on the genetic evaluation model of beef cattle composite

Dados de bovinos compostos foram analisados para avaliar o efeito da epistasia nos modelos de avaliação genética. As características analisadas foram os pesos aos 205 (P205) e 390 dias (P390) e perímetro escrotal aos 390 dias (PE390). As análises foram realizadas pela metodologia de máxima verossimilhança considerando-se dois modelos: o modelo 1 incluiu como covariáveis os efeitos aditivos diretos e maternos, e os não aditivos das heterozigoses para os efeitos diretos e para o materno total, e o modelo 2 considerou também o efeito direto de epistasia. Para comparação dos modelos, foram utilizados o critério de informação de Akaike (AIC) e o critério de informação Bayesiano de Schwartz (BIC), e o teste de razão de verossimilhança. A inclusão da epistasia no modelo de avaliação genética pouco alterou as estimativas de componentes de (co)variâncias genéticas aditivas e, consequentemente, as herdabilidades. O teste de verossimilhança e o critério de Akaike sugeriram que o modelo 2, que inclui a epistasia, apresentou maior aderência aos dados para todas as características analisadas. O critério BIC indicou este modelo como o melhor apenas para P205. Para análise genética dessa população, o modelo que considerou o efeito de epistasia foi o mais adequado.

Composite bovine data was analyzed with the objective of evaluating the effect of the epistasis parameter in the models of genetic evaluation. The analyzed characteristics were weight at 205 (W205) and 390 days (P390), and scrotal circumference at 390 days (SC390). The analysis were done by the maximum likelihood method, considering two models: model 1, which included as covariates the direct and maternal additive effects, and non-additive of the heterozygosis for the direct and total maternal, and model 2, which also considered the direct epistasis direct. The Akaike Information Criteria (AIC) and the Bayesiano of Schwartz Information Criteria (BIC) were used for the comparison of the models and the test of ratio of likelihood. The inclusion of the epistasis effects on the model of the genetic evaluation did not alter much the estimation of the genetic additive (co)variances components and, consequently the heritability. However, it was significantly superior by the likelihood ratio test for the studied characteristics. Through the BIC, model 2 was more adequate only for W205. For the genetic analysis of that population the model that considers the epitasis is the more adequate.

Efeitos genéticos e ambientais sobre a idade à primeira concepção de fêmeas suínas / Estimates of genetic and environmental effects on age at first conception of gilts

The genetic and environmental factors that affect age at first conception (AFC) of gilts were evaluated, using 466 observations of Dalland animals (C-40). The software program MTDFREML was used to assess the genetic parameters on an animal model that included as fixed effect, contemporary group and, as random effects, the additive genetic, the common litter and the error. Mean value of AFC was 241.12±25.9 days, with CV of 8.5 percent. Variance analysis showed that year (P<0.01), season (P<0.01) and herd effects (P<0.01) were important sources of variation of AFC. The throat effect (P=0.34) was not important for the AFC, but the mother of the gilts (P<0.01) was an important source of variation. The heritability estimate was 0.44±0.14 that this trait would yield genetic gain as a response to the selection.

A Novel Genetic Polymorphism and Its Genetic Effects of Porcine Myogenin Gene in Intron 1 / 中国生物化学与分子生物学报

Single-nucleotide polymorphisms of the MyoG gene were tested using PCR-SSCP from 73 Landrace pigs, 68 Large White pigs, 57 Yimeng pigs and 83 Laiwu pigs. The effects of the MyoG gene on the birth weight, the average daily gain, the meat tenderness, and the backfat thickness were also analyzed. On the basis of the DNA sequence (M14331) of the porcine MyoG gene, primers were designed to amplify MyoG gene. One polymorphism was found in the amplified region of intron 1, in which two alleles ( A, and B) and three genotypes (AA, AB, and BB ) were examined. A G→ C transition was detected at 2 943 locus by sequencing the homozygotes. The results show that: ( 1 ) The Large White breed differed significantly ( P ＜0.05) in genotype distribution from the Landrace, the Laiwu and the Yimeng breeds;and the Laiwu breed differed significantly( P ＜ 0.05) in genotype distribution from the Landrace and the Yimeng breeds; whereas no significant differences( P ＞ 0.05) were found in genotype distribution between the Landrace and the Yimeng breeds. (2) On the basis of the fixed effect model, significant differences ( P ＜ 0.05) were found in the birth weight and the tenderness among the different MyoG genotypes, whereas no significant differences ( P ＞ 0.05)existed in the average daily gain and the backfat thickness. (3) Using least square analysis, it was seen that significant differences ( P ＜ 0.05) exist in the meat tenderness between the individuals of the BB genotypes and those of the AA genotypes; and significant differences ( P ＜ 0.05 ) were found in the backfat thickness compared the pigs of the AA genotypes with the pigs of the AB, BB genotypes. These results suggest that the MyoG genotype has significant effects on the meat quality, the growth rate, and the backfat thickness,therefore MyoG gene can be used in marker-assisted selection to improve meat quality and growth rate, and to accelerate the breeding progress.