INTRODUCTION: Given the physiological role of placental growth hormone (PGH) during intrauterine development and growth, genetic variation in the coding Growth hormone 2 (GH2) gene may modulate developmental programming of adult stature. Two major GH2 variants were described worldwide, determined by single polymorphism (rs2006123; c.171 + 50C > A). We sought to study whether GH2 variants may contribute to adult anthropometric measurements. METHODS: Genotyping of GH2 SNP rs2006123 by RFLP, testing its genetic association with adult height and Body Mass Index (BMI) by linear regression analysis, and combining the results of three individual study samples in meta-analysis. STUDY SAMPLES: HYPEST (Estonia), n = 1464 (506 men/958 women), CADCZ (Czech), n = 871 (518/353); UFA (Bashkortostan), n = 954 (655/299); meta-analysis, n = 3289 (1679/1610). RESULTS: Meta-analysis across HYPEST, CADCZ and UFA samples (n = 3289) resulted in significant association of GH2 rs2006123 with height (recessive model: AA-homozygote effect: beta (SE) = 1.26 (0.46), P = 5.90 × 10⁻³; additive model: A-allele effect: beta (SE) = 0.45 (0.18), P = 1.40 × 10⁻²). Among men (n = 1679), the association of the A-allele with taller stature remained significant after multiple-testing correction (additive effect: beta = 0.86 (0.28), P = 1.83 × 10⁻³). No association was detected with BMI. Notably, rs2006123 was in strong LD (r² ≥ 0.87) with SNPs significantly associated with height (rs2665838, rs7209435, rs11658329) and mapped near GH2 in three independent meta-analyses of GWA studies. CONCLUSIONS: This is the first study demonstrating a link between a placental gene variant and programming of growth potential in adulthood. The detected association between PGH encoding GH2 and adult height promotes further research on the role of placental genes in prenatal programming of human metabolism.

• Keywords
• Association study, Developmental programming, GH2 gene, Human height and BMI, Placental growth hormone, Polymorphism,
• MeSH
• Adult MeSH
• Gene Frequency MeSH
• Genetic Association Studies MeSH
• Body Mass Index MeSH
• Polymorphism, Single Nucleotide * MeSH
• Middle Aged MeSH
• Humans MeSH
• Multigene Family MeSH
• Placental Hormones genetics   metabolism   MeSH
• Growth Hormone genetics   metabolism   MeSH
• Aged MeSH
• Pregnancy MeSH
• Body Height MeSH
• Linkage Disequilibrium MeSH
• Bone Development * MeSH
• Fetal Development * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Bashkiria MeSH
• Czech Republic MeSH
• Estonia MeSH
• Names of Substances
• GH2 protein, human MeSH Browser
• Placental Hormones MeSH
• Growth Hormone MeSH

Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.

• Keywords
• Non-Alcoholic Fatty Liver Disease, developmental programming, intra-abdominal fat, maternal nutrition, obesity,
• MeSH
• Alanine Transaminase blood   MeSH
• Aspartate Aminotransferases blood   MeSH
• Maternal Nutritional Physiological Phenomena * MeSH
• Liver metabolism   MeSH
• Blood Glucose metabolism   MeSH
• Disease Models, Animal MeSH
• Mice, Knockout MeSH
• Mice, Obese MeSH
• Mice MeSH
• Obesity genetics   MeSH
• Perinatal Care MeSH
• Receptor, Melanocortin, Type 4 deficiency   genetics   MeSH
• Gene Expression Regulation MeSH
• Pregnancy MeSH
• Triglycerides blood   MeSH
• Prenatal Exposure Delayed Effects genetics   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alanine Transaminase MeSH
• Aspartate Aminotransferases MeSH
• Blood Glucose MeSH
• MC4R protein, mouse MeSH Browser
• Receptor, Melanocortin, Type 4 MeSH
• Triglycerides MeSH

The developmental competence of oocytes is acquired progressively during folliculogenesis and is linked to follicular size. It has been documented that oocytes originating from larger follicles exhibit a greater ability to develop to the blastocyst stage. The differences in cytoplasmic factors such as mRNA transcripts could explain the differences in oocyte developmental potential. We used bovine oligonucleotide microarrays to characterize differences between the gene expression profiles of germinal vesicle stage (GV) oocytes with greater developmental competence from medium follicles (MF) and those with less developmental competence from small follicles (SF). After normalizing the microarray data, our analysis found differences in the level of 60 transcripts (≥1.4 fold), corresponding to 49 upregulated and 11 downregulated transcripts in MF oocytes compared to SF oocytes. The gene expression data were classified according to gene ontology, the majority of the genes were associated with the regulation of transcription, translation, the cell cycle, and mitochondrial activity. A subset of 16 selected genes was validated for GV oocytes by quantitative real-time RT-PCR; significant differences (P˂0.01) were found in the level of TAF1A, MTRF1L, ATP5C1, UBL5 and MAP3K13 between the MF and SF oocytes. After maturation the transcript level remained stable for ATP5F1, BRD7, and UBL5 in both oocyte categories. The transcript level of another 13 genes substantially dropped in the MF and/or SF oocytes. It can be concluded that the developmental competence of bovine oocytes and embryos may be a quantitative trait dependent on small changes in the transcription profiles of many genes.

• Keywords
• Bovine, Developmental competence, Embryo, Oocyte, Transcription,
• MeSH
• Embryonic Development genetics   MeSH
• Fertilization in Vitro MeSH
• Oocytes metabolism   physiology   MeSH
• Oogenesis genetics   MeSH
• Ovarian Follicle metabolism   MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Cattle genetics   physiology   MeSH
• Gene Expression Profiling MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Cattle genetics   physiology   MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Pronuclear transfer has been successfully used in human-assisted reproduction to suppress the adverse effects of a defective oocyte cytoplasm or to bypass an idiopathic developmental arrest. However, the effects of the initial parental genome remodelling in a defective cytoplasm on the subsequent development after pronucleus transfer have not been systematically studied. By performing pronuclear transfer in pre-replication and post-replication mouse embryos, we show that the timing of the procedure plays a critical role. Although apparently morphologically normal blastocysts were obtained in both pre- and post-replication pronuclear transfer groups, post-replication pronuclear transfer led to a decrease in developmental competence and profound changes in embryonic gene expression. By inhibiting the replication in the abnormal cytoplasm before pronuclear transfer into a healthy cytoplasm, the developmental potential of embryos could be largely restored. This shows that the conditions under which the first embryonic replication occurs strongly influence developmental potential. Although pronuclear transfer is the method of choice for mitigating the impact of a faulty oocyte cytoplasm on early development, our results show that the timing of this intervention should be restricted to the pre-replication phase.

• Keywords
• DNA damage, developmental rate, embryo, pronuclear transfer, replication,
• MeSH
• Blastocyst * metabolism   cytology   MeSH
• Cell Nucleus metabolism   MeSH
• Time Factors MeSH
• Cytoplasm metabolism   MeSH
• Embryo, Mammalian MeSH
• Embryonic Development * MeSH
• Mice MeSH
• Oocytes metabolism   cytology   MeSH
• Nuclear Transfer Techniques * MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Developmental coordination disorder (DCD) is described as a motor skill disorder characterized by a marked impairment in the development of motor coordination abilities that significantly interferes with performance of daily activities and/or academic achievement. Since some electrophysiological studies suggest differences between children with/without motor development problems, we prepared an experimental protocol and performed electrophysiological experiments with the aim of making a step toward a possible diagnosis of this disorder using the event-related potentials (ERP) technique. The second aim is to properly annotate the obtained raw data with relevant metadata and promote their long-term sustainability. RESULTS: The data from 32 school children (16 with possible DCD and 16 in the control group) were collected. Each dataset contains raw electroencephalography (EEG) data in the BrainVision format and provides sufficient metadata (such as age, gender, results of the motor test, and hearing thresholds) to allow other researchers to perform analysis. For each experiment, the percentage of ERP trials damaged by blinking artifacts was estimated. Furthermore, ERP trials were averaged across different participants and conditions, and the resulting plots are included in the manuscript. This should help researchers to estimate the usability of individual datasets for analysis. CONCLUSIONS: The aim of the whole project is to find out if it is possible to make any conclusions about DCD from EEG data obtained. For the purpose of further analysis, the data were collected and annotated respecting the current outcomes of the International Neuroinformatics Coordinating Facility Program on Standards for Data Sharing, the Task Force on Electrophysiology, and the group developing the Ontology for Experimental Neurophysiology. The data with metadata are stored in the EEG/ERP Portal.

• Keywords
• developmental coordination disorder, electroencephalography, event-related potentials, reaction time, visual and audio stimulation,
• MeSH
• Acoustic Stimulation MeSH
• Data Curation MeSH
• Child MeSH
• Electroencephalography MeSH
• Evoked Potentials MeSH
• Comorbidity MeSH
• Quantitative Trait, Heritable MeSH
• Humans MeSH
• Computer Simulation MeSH
• Motor Skills Disorders diagnosis   MeSH
• Reaction Time MeSH
• Reproducibility of Results MeSH
• Software MeSH
• Photic Stimulation MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Mammalian oocyte development depends on the temporally controlled translation of maternal transcripts, particularly in the coordination of meiotic and early embryonic development when transcription has ceased. The translation of mRNA is regulated by various RNA-binding proteins. We show that the absence of cytoplasmic polyadenylation element-binding protein 3 (CPEB3) negatively affects female reproductive fitness. CPEB3-depleted oocytes undergo meiosis normally but experience early embryonic arrest due to a disrupted transcriptome, leading to aberrant protein expression and the subsequent failure of embryonic transcription initiation. We found that CPEB3 stabilizes a subset of mRNAs with a significantly longer 3'UTR that is enriched in its distal region with cytoplasmic polyadenylation elements. Overall, our results suggest that CPEB3 is an important maternal factor that regulates the stability and translation of a subclass of mRNAs that are essential for the initiation of embryonic transcription and thus for embryonic development.

• Keywords
• embryo, mRNA, oocyte, translation,
• MeSH
• 3' Untranslated Regions genetics   MeSH
• Embryonic Development genetics   MeSH
• Meiosis genetics   MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Mice MeSH
• Oocytes * metabolism   MeSH
• Polyadenylation MeSH
• RNA-Binding Proteins * metabolism   genetics   MeSH
• RNA Stability genetics   MeSH
• Gene Expression Regulation, Developmental MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3' Untranslated Regions MeSH
• Cpeb3 protein, mouse MeSH Browser
• RNA, Messenger MeSH
• RNA-Binding Proteins * MeSH

Pre-implantation embryos derived by in vitro fertilization differ in their developmental potential from embryos obtained in vivo. In order to characterize changes in gene expression profiles caused by in vitro culture environment, we employed microarray constructed from bovine oocyte and preimplantation embryo-specific cDNAs (BlueChip, Université Laval, Québec). The analysis revealed changes in the level of 134 transcripts between in vitro derived (cultured in COOK BVC/BVB media) and in vivo derived 4-cell stage embryos and 97 transcripts were differentially expressed between 8-cell stage in vitro and in vivo embryos. The expression profiles of 7 selected transcripts (BUB3, CUL1, FBL, NOLC1, PCAF, GABPA and CNOT4) were studied in detail. We have identified a switch from Cullin 1-like transcript variant 1 to Cullin 1 transcript variant 3 (UniGene IDs BT.36789 and BT.6490, respectively) expressions around the time of bovine major gene activation (8-cell stage). New fibrillarin protein was detected by immunofluorescence already in early 8-cell stage and this detection correlated with increased level of fibrillarin mRNA. The qRT-PCR analysis revealed significant differences in the level of BUB3, NOLC1, PCAF, GABPA and CNOT4 gene transcripts between in vivo derived (IVD) and in vitro produced (IVP) embryos in late 8-cell stage. The combination of these genes represents a suitable tool for addressing questions concerning normal IVD embryo development and can be potentially useful as a marker of embryo quality in future attempts to optimize in vitro culture conditions.

• MeSH
• Blastocyst metabolism   MeSH
• Embryonic Development genetics   MeSH
• Cullin Proteins genetics   metabolism   MeSH
• Embryo Culture Techniques veterinary   MeSH
• Culture Media MeSH
• Molecular Sequence Data MeSH
• Base Sequence MeSH
• Sequence Alignment MeSH
• Cattle MeSH
• Gene Expression Profiling * MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cullin 1 MeSH Browser
• Cullin Proteins MeSH
• Culture Media MeSH

Reintroduction of captive-bred individuals into the wild is an important conservation activity. However, environmental conditions can influence developmental programming, potentially causing metabolic disorders in adults. These effects are investigated here for the first time in an endangered species. Using body weight and feed intake data for Iberian lynx (Lynx pardinus) (n = 22), we compared the growth of captive versus wild born and/or reared individuals. Captive-born individuals gained weight as a function of calorie intake, unlike wild-born individuals. When compared with females reared in the wild, captive-reared females achieved a larger body size, without evidence of obesity. Captivity-associated changes to metabolic programming may compromise survival in the wild if an increased body size incurs a greater energy requirement. Large body size may also confer a competitive advantage over smaller, wild-born individuals, disrupting the social organisation of existing wild populations, and inferring long-term implications for the phenotypic composition of wild populations.

• MeSH
• Behavior, Animal MeSH
• Energy Intake MeSH
• Lynx growth & development   metabolism   psychology   MeSH
• Endangered Species MeSH
• Social Behavior MeSH
• Social Isolation MeSH
• Body Weight MeSH
• Conservation of Natural Resources MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The aim of this study was to compare the expression of selected genes in bovine embryos developed from oocytes with different developmental competence. Four oocyte populations were collected, separately either from small (2-5 mm) or medium (6-10 mm) follicles, in the growth/stagnation (G/S) or dominance/regression (D/R) stage of the first follicular wave. They were matured, fertilized and cultured to D7 or D8 blastocysts by a standard protocol. Poly (A)+ mRNA was extracted from pooled blastocysts and the expression of bax-alpha (Bax), connexin 43 (Cx 43) and connexin 31 (Cx 31) was estimated using real-time RT-PCR. The cleavage rates were significantly higher in oocytes collected from both medium and small follicles, (p < or = 0.05 and p < or = 0.01, respectively) in the G/S than in the D/R stage. There were no significant differences in the D7 blastocyst rates between oocytes from both medium and small follicles in the G/S or D/R stage. But the D8 blastocyst rate was significantly higher in oocytes from small follicles in the G/S stage compared with those in the D/R stage. The relative abundance of Bax and Cx 31 made no significant difference in both D7 and D8 blastocysts developed from oocytes collected from medium or small follicles in the G/S or D/R stages. But the relative abundance of the Cx 43 transcript was significantly higher in D8 blastocysts developed from oocytes collected from both medium and small follicles in the G/S stage compared with those in the D/R stage. We conclude that the relative abundance of Cx 43 can be used as a marker of developmental potential for embryos derived from oocytes with different developmental competence because the level of Cx 43 transcript was greater in embryos derived from oocytes with greater developmental competence compared with those derived from oocytes with lesser developmental competence.

• MeSH
• Blastocyst physiology   MeSH
• Embryo, Mammalian metabolism   MeSH
• Embryonic Development MeSH
• Gene Expression * MeSH
• Connexin 43 genetics   MeSH
• Connexins genetics   MeSH
• RNA, Messenger analysis   isolation & purification   MeSH
• Oocytes physiology   MeSH
• Ovarian Follicle cytology   growth & development   MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• bcl-2-Associated X Protein genetics   MeSH
• Cattle embryology   MeSH
• Animals MeSH
• Check Tag
• Cattle embryology   MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• GJB3 protein, human MeSH Browser
• Connexin 43 MeSH
• Connexins MeSH
• RNA, Messenger MeSH
• bcl-2-Associated X Protein MeSH

Embryotoxic effects of CdCl2 administered in a single dose of 2.0, 4.0 or 6.0 mg/kg body weight to randombred ICR mice (Velaz) on the 8th, 9th, 10th, 11th, 12th, 13th or 14th day of pregnancy were studied. The embryolethal effect, being highest after treatment with 6.0 mg/kg CdCl2 on the 12th and 13th day of pregnancy (50.0 and 61.3%) was not significantly correlated to the day of treatment. Among survivors, foetuses with haemorrhagic bullae, limb malformations, exencephaly, cleft palate, open eyelids and tail deformities occurred. Mainly the right-sided limbs were malformed. The administration of 2.0 and 4.0 mg/kg CdCl2 on the 10th day of pregnancy induced fore limb polydactylies, whereas with the dose of 6.0 mg also oligodactylies were induced. The foetal body weight was reduced only by a dose of 6.0 mg CdCl2 administered on the 12th day of pregnancy. Reduction of the thymus weight was a constant effect of treatment with the higher doses of cadmium from the 9th to the 14th day of pregnancy.

• MeSH
• Abnormalities, Drug-Induced MeSH
• Embryonic and Fetal Development drug effects   MeSH
• Cadmium toxicity   MeSH
• Mice, Inbred ICR MeSH
• Mice MeSH
• Pregnancy MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cadmium MeSH