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2.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38282422

RESUMO

Cow temperament at parturition may be mostly a measure of aggressiveness. The heritability of cow temperament at parturition in Bos taurus cows has been reported to be low. The objectives of this study were to estimate the heritability of cow temperament at parturition, conduct a genome-wide association analysis of cow temperament at the time of parturition, and estimate the correspondence of cow temperament at the time of parturition with cow productive performance and early-life temperament traits in Bos indicus crossbreds. Cow temperament was assessed from 1 to 5 indicating increasing levels of aggressiveness of cows (937 cows and 4,337 parturitions) from 2005 to 2022. Estimates of heritability and repeatability were 0.12 ±â€…0.024 and 0.24 ±â€…0.018. The estimates of proportion of phenotypic variance were 0.13 ±â€…0.019 and 0.02 ±â€…0.011 for permanent and maternal permanent environmental components, respectively. Estimates of heritability for maximum lifetime temperament score and proportions of temperament scores >1 were 0.18 ±â€…0.07 and 0.13 ±â€…0.072. Within cycles (generations), 2-yr-old cows had lower temperament score means than cows in most other age categories. There were low to moderate positive estimates of unadjusted correlation coefficients (r = 0.22 to 0.29; P < 0.05) of unadjusted temperament score with temperament measured on the same females when they were 8 mo old. There were low to moderate positive estimates of correlation coefficients (r = 0.09 to 0.37; P < 0.05) of unadjusted temperament score with calving rate, weaning rate, weaning weight per cow exposed, and weaning weight per 454 kg cow weight at weaning. Cows with the lowest temperament score had lower (P < 0.05) calving and weaning rate than cows in other temperament categories. Within 3 of 5 cycles, cows with the lowest temperament score (totally docile) had lower (P < 0.05) weaning weight per cow exposed than cows in other temperament categories. There were 2 SNP on BTA 4 associated with maximum lifetime temperament score (FDR < 0.05). The non-genetic influence of a cow's mother was documented in her own temperament measured at the time of calving; this may be a consequence of learned behavior. Less aggressiveness displayed by cows at the time of calving may be accompanied by lower reproductive and maternal performance.


Cow temperament was evaluated in 1/2 Nellore 1/2 Angus cows from four distinct generations (five herds) from 2005 to 2022. Cows were scored when their calves were processed (1 d age) as 1 = totally docile, 2 = protective, but not aggressive, 3 = moderately aggressive when calf is disturbed, 4 = very aggressive when calf is disturbed, and 5 = very aggressive even when calf is not disturbed. Similar to results in Bos taurus cows, the heritability of this trait was low. The repeatability was more moderate, indicating that additional records from a cow would be beneficial for selection purposes. Young cows had lower scores, indicating more docile behavior. This may be because a strong maternal protective instinct develops and strengthens over time. Temperament measured when cows were 8 mo old was moderately associated with their temperament as mature cows at the time of parturition. Cows with low temperament scores (more docile) had, in several cases, lower reproductive performance and production. Experiential accumulation appears to be important for cow temperament near the time of calving, including the cow's experience as a calf from her dam.


Assuntos
Estudo de Associação Genômica Ampla , Temperamento , Gravidez , Feminino , Bovinos/genética , Animais , Estudo de Associação Genômica Ampla/veterinária , Parto/genética , Reprodução/genética , Desmame
3.
Int J Mol Sci ; 24(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38069145

RESUMO

Parturition is the final and essential step for mammalian reproduction. While the uterus is quiescent during pregnancy, fundamental changes arise in the myometrial contractility, inducing fetal expulsion. Extracellular matrix (ECM) remodeling is fundamental for these events. The gelatinases subgroup of matrix metalloproteinases (MMPs), MMP2 and MMP9, participate in uterine ECM remodeling throughout pregnancy and parturition. However, their loss-of-function effect is unknown. Here, we determined the result of eliminating Mmp2 and/or Mmp9 on parturition in vivo, using single- and double-knockout (dKO) mice. The dystocia rates were measured in each genotype, and uterine tissue was collected from nulliparous synchronized females at the ages of 2, 4, 9 and 12 months. Very high percentages of dystocia (40-55%) were found in the Mmp2-/- and dKO females, contrary to the Mmp9-/- and wild-type females. The histological analysis of the uterus and cervix revealed that Mmp2-/- tissues undergo marked structural alterations, including highly enlarged myometrial, endometrial and luminal cavity. Increased collagen deposition was also demonstrated, suggesting a mechanism of extensive fibrosis in the Mmp2-/- myometrium, which may result in dystocia. Overall, this study describes a new role for MMP2 in myometrium remodeling during mammalian parturition process, highlighting a novel cause for dystocia due to a loss in MMP2 activity in the uterine tissue.


Assuntos
Distocia , Metaloproteinase 9 da Matriz , Animais , Feminino , Camundongos , Gravidez , Distocia/genética , Distocia/patologia , Mamíferos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Miométrio/patologia , Parto/genética
4.
Nat Genet ; 55(4): 559-567, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37012456

RESUMO

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.


Assuntos
Parto , Nascimento Prematuro , Gravidez , Recém-Nascido , Feminino , Humanos , Peso ao Nascer/genética , Parto/genética , Nascimento Prematuro/genética , Idade Gestacional
5.
Inflamm Res ; 72(4): 797-812, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36879064

RESUMO

OBJECTIVES: Sterile inflammation of fetal membranes is an indispensable event of normal parturition. However, triggers of sterile inflammation are not fully resolved. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver. Fetal membranes can also synthesize SAA1 but its functions are not well defined. Given the role of SAA1 in the acute phase response to inflammation, we postulated that SAA1 synthesized in the fetal membranes may be a trigger of local inflammation at parturition. METHODS: The changes of SAA1 abundance in parturition were studied in the amnion of human fetal membranes. The role of SAA1 in chemokine expression and leukocyte chemotaxis was examined in cultured human amnion tissue explants as well as primary human amnion fibroblasts. The effects of SAA1 on monocytes, macrophages and dendritic cells were investigated in cells derived from a human leukemia monocytic cell line (THP-1). RESULTS: SAA1 synthesis increased significantly in human amnion at parturition. SAA1 evoked multiple chemotaxis pathways in human amnion fibroblasts along with upregulation of a series of chemokines via both toll-like receptor 4 (TLR4) and formyl peptide receptor 2 (FPR2). Moreover, SAA1-conditioned medium of cultured amnion fibroblasts was capable of chemoattracting virtually all types of mononuclear leukocytes, particularly monocytes and dendritic cells, which reconciled with the chemotactic activity of conditioned medium of cultured amnion tissue explants collected from spontaneous labor. Furthermore, SAA1 could induce the expression of genes associated with inflammation and extracellular matrix remodeling in monocytes, macrophages and dendritic cells derived from THP-1. CONCLUSIONS: SAA1 is a trigger of sterile inflammation of the fetal membranes at parturition.


Assuntos
Âmnio , Parto , Gravidez , Feminino , Humanos , Âmnio/metabolismo , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Parto/genética , Parto/metabolismo , Membranas Extraembrionárias/metabolismo , Quimiocinas/metabolismo , Inflamação/metabolismo , Proteína Amiloide A Sérica
6.
J Psychosom Res ; 168: 111210, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36898314

RESUMO

OBJECTIVE: To investigate the association of postpartum depressive symptoms (PDS) and self-harm ideation with n-methyl-d-aspartate (NMDA) receptor GRIN2B and GRIN3A gene polymorphisms and other risk factors in women undergoing cesarean section. METHODS: A total of 362 parturients undergoing cesarean section under lumbar anesthesia were selected and their postpartum depression level was assessed by the Edinburgh Postpartum Depression Scale (EPDS) at 42 days postpartum, with an EPDS score of 9/10 as the cut-off value. Three GRIN2B SNP loci (rs1805476, rs3026174, rs4522263) and five GRIN3A SNP loci (rs1983812, rs2050639, rs2050641, rs3739722, rs10989563) were selected for genotype detection. The role of each SNP, linkage disequilibrium and haplotypes in the development of postpartum depression was analyzed. Logistic regression analysis was performed for related risk factors. RESULTS: PDS incidence was 16.85%, and self-harm ideation incidence was 13.54%. Univariate analysis showed that GRIN2B rs1805476, rs3026174 and rs4522263 gene polymorphisms were associated with PDS (p < 0.05), with GRIN2B rs4522263 gene also associated with maternal self-harm ideation. GRIN3A rs1983812, rs2050639, rest rs2050641, rs3739722 and rs10989563 alleles were not associated with PDS. Logistic regression analysis indicated that high pregnancy stress, as well as rs1805476 and rs4522263 alleles were PDS risk factors following cesarean delivery. GRIN2B (TTG p = 0.002) and GRIN3A (TGTTC p = 0.002) haplotypes were associated with the lower PDS incidence and higher PDS incidence respectively. CONCLUSION: GRIN2B rs1805476 GG genotype, rs4522263 CC genotype and high stress during pregnancy were risk factors for PDS, whilst a significantly higher incidence of self-harm ideation was evident in parturients carrying GRIN2B rs4522263 CC genotype.


Assuntos
Cesárea , Depressão Pós-Parto , Receptores de N-Metil-D-Aspartato , Comportamento Autodestrutivo , Feminino , Humanos , Gravidez , Cesárea/efeitos adversos , Cesárea/psicologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/genética , Depressão/psicologia , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Depressão Pós-Parto/genética , Depressão Pós-Parto/psicologia , População do Leste Asiático/genética , População do Leste Asiático/psicologia , Genótipo , Haplótipos , Parto/genética , Parto/psicologia , Polimorfismo Genético , Período Pós-Parto , Estudos Prospectivos , Receptores de N-Metil-D-Aspartato/genética , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/etiologia , Comportamento Autodestrutivo/genética , Comportamento Autodestrutivo/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/genética
7.
Anim Sci J ; 94(1): e13807, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36690423

RESUMO

The economic efficiency of fur animal farms is considerably influenced by reproductive performance. The objectives of this study are to determine the effects of individual and maternal inbreeding, birth year, and dam and sire age on litter size at birth (LSB) and at weaning (LSW) and on preweaning mortality (PWM) in a red fox herd under long-term selection, and to determine the heritability of these traits. In total, 37,973 pedigreed individuals were used to calculate the inbreeding coefficients, based on records of 14,527 litters of 3856 dams born from the year 1958 to 2015. Two data sets (all data and data for the Polish variety) were analyzed. The highest heritability was estimated for PWM (0.292, 0.306) and the lowest for LSW (0.114, 0.115). In contrast to paternal and maternal inbreeding, litter inbreeding was found to exert a significant influence. The absence of significant effects of most varieties may suggest relatively large genetic similarity in the world red fox population. This corresponds with the similarity of the results obtained for the total herd and for the Polish variety. Favorable genetic trends were observed for the studied traits, indicating that the selection applied had been a relatively effective approach to improving these traits.


Assuntos
Raposas , Parto , Gravidez , Feminino , Animais , Peso Corporal/genética , Teorema de Bayes , Parto/genética , Reprodução/genética , Tamanho da Ninhada de Vivíparos/genética , Desmame , Seleção Genética
8.
J Steroid Biochem Mol Biol ; 224: 106160, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35931328

RESUMO

Myometrial contraction is stringently controlled throughout pregnancy and parturition. Progesterone signaling, effecting through the progesterone receptor (PR), is pivotal in modulating uterine activity. Evidence has shown that two major PR isoforms, PR-A and PR-B, have distinct activities on gene regulation, and the ratio between these isoforms determines the contractility of the myometrium at different gestational stages. Herein, we focus on the regulation of PR activity in the myometrium, especially the differential actions of the two PR isoforms, which maintain uterine quiescence during pregnancy and regulate the switch to a contractile state at the onset of labor. To demonstrate the PR regulatory network and its mechanisms of actions on myometrial activity, we summarized the findings into three parts: Regulation of PR Expression and Isoform Levels, Progesterone Receptor Interacting Factors, and Biological Processes Regulated by Myometrial Progesterone Receptor Isoforms. Recent genomic and epigenomic data, from human specimens and mouse models, are recruited to support the existing knowledge and offer new insights and future directions in myometrial biology.


Assuntos
Contração Muscular , Miométrio , Parto , Gravidez , Receptores de Progesterona , Animais , Feminino , Humanos , Camundongos , Gravidez/genética , Gravidez/metabolismo , Miométrio/metabolismo , Parto/genética , Parto/metabolismo , Progesterona/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Contração Muscular/genética
9.
JCI Insight ; 7(5)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260533

RESUMO

Parturition is a well-orchestrated process characterized by increased uterine contractility, cervical ripening, and activation of the chorioamniotic membranes; yet, the transition from a quiescent to a contractile myometrium heralds the onset of labor. However, the cellular underpinnings of human parturition in the uterine tissues are still poorly understood. Herein, we performed a comprehensive study of the human myometrium during spontaneous term labor using single-cell RNA sequencing (scRNA-Seq). First, we established a single-cell atlas of the human myometrium and unraveled the cell type-specific transcriptomic activity modulated during labor. Major cell types included distinct subsets of smooth muscle cells, monocytes/macrophages, stromal cells, and endothelial cells, all of which communicated and participated in immune (e.g., inflammation) and nonimmune (e.g., contraction) processes associated with labor. Furthermore, integrating scRNA-Seq and microarray data with deconvolution of bulk gene expression highlighted the contribution of smooth muscle cells to labor-associated contractility and inflammatory processes. Last, myometrium-derived single-cell signatures can be quantified in the maternal whole-blood transcriptome throughout pregnancy and are enriched in women in labor, providing a potential means of noninvasively monitoring pregnancy and its complications. Together, our findings provide insights into the contributions of specific myometrial cell types to the biological processes that take place during term parturition.


Assuntos
Trabalho de Parto , Miométrio , Células Endoteliais , Feminino , Humanos , Trabalho de Parto/genética , Trabalho de Parto/metabolismo , Miométrio/metabolismo , Parto/genética , Parto/metabolismo , Gravidez , Transcriptoma
10.
Biol Rev Camb Philos Soc ; 97(3): 851-873, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34939297

RESUMO

Preterm birth occurs worldwide and is associated with high morbidity, mortality, and economic cost. Although several risk factors associated with parturition and preterm birth have been identified, mechanisms underlying this syndrome remain unclear, thereby limiting the implementation of interventions for prevention and management. Known triggers of preterm birth include conditions related to inflammatory and immunological pathways, as well as genetics and maternal history. Importantly, epigenetics, which is the study of heritable phenotypic changes that occur without alterations in the DNA sequence, may play a role in linking social and environmental risk factors for preterm birth. Epigenetic approaches to the study of preterm birth, including analyses of the effects of microRNAs, long non-coding RNAs, DNA methylation, and histone modification, have contributed to an improved understanding of the molecular bases of both term and preterm birth. Additionally, epigenetic modifications have been linked to factors already associated with preterm birth, including obesity and smoking. The prevention and management of preterm birth remains a challenge worldwide. Although epigenetic analysis provides valuable insights into the causes and risk factors associated with this syndrome, further studies are necessary to determine whether epigenetic approaches can be used routinely for the diagnosis, prevention, and management of preterm birth.


Assuntos
MicroRNAs , Nascimento Prematuro , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Recém-Nascido , MicroRNAs/genética , Parto/genética , Gravidez , Nascimento Prematuro/genética
11.
Genes (Basel) ; 12(12)2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34946830

RESUMO

Selenium (Se) is an essential micronutrient for growth and immune function in beef cattle. We previously showed that supranutritional maternal organic Se supplementation during late pregnancy improves immune function in their newborn calves; however, the effects of maternal organic Se-supplementation on fetal programming during different pregnancy stages have yet to be elucidated. Herein, we investigated the effects of supranutritional maternal organic Se-supplementation in different pregnancy trimesters on their beef calf's genome-wide transcriptome profiles. Within 12 to 48 h of birth, whole blood and Longissimus dorsi (LD) muscle biopsies were collected from calves born to 40 crossbred Angus cows that received, except for the control group (CTR), Se-yeast boluses (105 mg of Se/wk) during the first (TR1), second (TR2), or third (TR3) trimester of gestation. Whole-blood Se concentrations of newborn calves increased from CTR, TR1, TR2 to TR3, whereas muscle Se concentrations of newborn calves were only increased in TR3 group. We identified 3048 unique differentially expressed genes (DEGs) across all group comparisons (FDR ≤ 0.05 and |log2FC| ≥ 1.5). Furthermore, we predicted 237 unique transcription factors that putatively regulate the DEGs. Independent of supplementation trimester, supranutritional maternal organic Se supplementation downregulated genes involved in adaptive immunity in all trimesters. Dependent on supplementation trimester, genes involved in muscle development were upregulated by TR3 Se supplementation and downregulated by TR1 Se-supplementation, and genes involved in collagen formation were downregulated by TR2 Se-supplementation. Supranutritional maternal organic Se supplementation in the last trimester of pregnancy resulted in upregulation of myosin and actin filament associated genes, potentially allowing for optimal muscle function and contraction. Our findings suggest a beneficial effect of supranutritional maternal organic Se supplementation during late gestation on Se-status and muscle development and function of newborn calves.


Assuntos
Músculos/metabolismo , Trimestres da Gravidez/efeitos dos fármacos , Selênio/administração & dosagem , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Ração Animal , Animais , Animais Recém-Nascidos/genética , Bovinos , Suplementos Nutricionais , Feminino , Parto/genética , Gravidez , Trimestres da Gravidez/genética
12.
Front Immunol ; 12: 722816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671346

RESUMO

During labor, a variety of coordinated physiological and biochemical events cause the myometrium to transition from a quiescent to contractile state; the molecular mechanisms responsible for this transition, however, remain unclear. To better understand this transition at a molecular level, the global transcriptome and proteome of human myometrial samples in labor and those not in labor were investigated through RNA sequencing (RNA-seq) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) via data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methods. Furthermore, an integrated proteotranscriptomic analysis was performed to explore biological processes and pathway alterations during labor; this analysis identified 1,626 differentially expressed mRNAs (1,101 upregulated, 525 downregulated) and 135 differentially expressed proteins (97 upregulated, 38 downregulated) in myometrium between nonlabor and in labor groups. The comprehensive results of these analyses showed that the upregulated mRNAs and proteins increased inflammation under hypoxia stress in the myometrium under labor, and related proteins and cytokines were validated by PRM and Luminex assays. Our study confirmed the biological process of inflammation and hypoxia in laboring myometrium at the transcriptome and proteome levels and provided recourse to discover new molecular and biological changes during labor.


Assuntos
Hipóxia/metabolismo , Trabalho de Parto/metabolismo , Miométrio/metabolismo , Parto/metabolismo , RNA Mensageiro/metabolismo , Transcriptoma , Adulto , Cromatografia Líquida , Citocinas/metabolismo , Feminino , Redes Reguladoras de Genes , Humanos , Inflamação/metabolismo , Trabalho de Parto/genética , Parto/genética , Gravidez , RNA Mensageiro/genética , Espectrometria de Massas em Tandem
13.
Nat Hum Behav ; 5(12): 1717-1730, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34211149

RESUMO

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.


Assuntos
Coito/fisiologia , Parto/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Fatores Etários , Feminino , Estudos de Associação Genética , Humanos , Masculino , Reprodução/genética
14.
Anim Reprod Sci ; 231: 106800, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34246040

RESUMO

Reproductive traits are important for farm profitability because failure to reproduce is the primary reason for culling animals. Study objectives were to estimate genetic parameters and evaluate the trends for reproductive traits. Age at first calving (AFC), gestation length (GL), postpartum interval to pregnancy (PPIP), calving interval (CI) and calving ease score (CE) were recorded. A total of 38,906 records were available from 2426 buffalo cows. There was evaluation of genetic parameters using three models. The first model was applied to the first three parities fitting animal as a random effect. There was also a repeatability model utilized where data from all parities were evaluated to estimate heritability and repeatability. There was also a bivariate model to estimate genetic correlations between reproductive traits. Heritability estimates ranged from 0.0001 to 0.12 for PPIP and CE, respectively. Repeatability estimates were low to moderate ranging from 0.13 to 0.38 for PPIP and GL, respectively. There were close genetic correlations of 0.99 and - 0.93 between PPIP-CI and GL-CE, respectively. Genetic correlations between the other reproductive traits were low to moderate. Genetic trends for all reproductive traits were negative with and of a small magnitude, and regression coefficients were significant only for AFC and PPIP. The results from the current study supported the urgent need, not only for genetic or genomic selection improvement programs, but also for improving the farm management practices for reproductive traits in Egyptian buffalo.


Assuntos
Búfalos/genética , Búfalos/fisiologia , Modelos Genéticos , Parto/fisiologia , Maturidade Sexual/genética , Animais , Cruzamento , Feminino , Lactação/genética , Lactação/fisiologia , Masculino , Parto/genética , Gravidez , Maturidade Sexual/fisiologia
15.
Biochem Soc Trans ; 49(2): 997-1011, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33860781

RESUMO

Cyclic adenosine monophosphate (cAMP) contributes to maintenance of a quiescent (relaxed) state in the myometrium (i.e. uterine smooth muscle) during pregnancy, which most commonly has been attributed to activation of protein kinase A (PKA). PKA-mediated phosphorylation of cytosolic contractile apparatus components in myometrial smooth muscle cells (mSMCs) are known to promote relaxation. Additionally, PKA also regulates nuclear transcription factor (TF) activity to control expression of genes important to the labour process; these are mostly involved in actin-myosin interactions, cell-to-cell connectivity and inflammation, all of which influence mSMC transition from a quiescent to a contractile (pro-labour) phenotype. This review focuses on the evidence that cAMP modulates the activity of TFs linked to pro-labour gene expression, predominantly cAMP response element (CRE) binding TFs, nuclear factor κB (NF-κB), activator protein 1 (AP-1) family and progesterone receptors (PRs). This review also considers the more recently described exchange protein directly activated by cAMP (EPAC) that may oppose the pro-quiescent effects of PKA, as well as explores findings from other cell types that have the potential to be of novel relevance to cAMP action on TF function in the myometrium.


Assuntos
AMP Cíclico/metabolismo , Regulação da Expressão Gênica , Músculo Liso/metabolismo , Miométrio/metabolismo , Parto/genética , Fatores de Transcrição/genética , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Humanos , Trabalho de Parto/genética , Trabalho de Parto/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Parto/metabolismo , Gravidez , Fatores de Transcrição/metabolismo
16.
Mol Hum Reprod ; 27(5)2021 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-33823545

RESUMO

The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for foetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1, progesterone receptors, oestrogen receptors, and nuclear factor kappa B, as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour-associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.


Assuntos
Miométrio/fisiologia , Parto/genética , Fatores de Transcrição/fisiologia , Animais , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Trabalho de Parto/genética , Gravidez , Transcrição Gênica
17.
Reprod Sci ; 28(3): 659-664, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33469878

RESUMO

Labor and vaginal delivery cause acute ischemic/hypoxic insult to the placenta. Previous studies demonstrate that placentas from high altitude non-natives showed blunted responses to ischemic/hypoxic insult caused by labor and vaginal birth, and there were some differences in the ATP/ADP production ratio. We hypothesized that adapted highlanders would not have a stress response to the acute hypoxia/ischemia of labor. Tibetan laboring (n = 10) and non-laboring (n = 5) and European descendants laboring (n = 10) and non-laboring (n = 5) high-altitude placentas were analyzed using genome-wide expression array analysis. There was no evidence for ischemic/hypoxic stress in high-altitude Tibetan laboring as compared with non-laboring placentas, while there were differences in gene expression between laboring and non-laboring placentas from high-altitude European descendants. Our results provide evidence for adaptation to acute hypoxic ischemic insult caused by labor and vaginal birth in placentas in a high-altitude native Tibetan population.


Assuntos
Aclimatação , Doença da Altitude/prevenção & controle , Altitude , Isquemia/prevenção & controle , Trabalho de Parto , Parto , Placenta/irrigação sanguínea , Circulação Placentária , Doença da Altitude/etiologia , Doença da Altitude/genética , Doença da Altitude/fisiopatologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Isquemia/etiologia , Isquemia/genética , Isquemia/fisiopatologia , Trabalho de Parto/genética , Análise de Sequência com Séries de Oligonucleotídeos , Parto/genética , Gravidez , Tibet , Transcriptoma
18.
Reprod Domest Anim ; 56(2): 370-373, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32996263

RESUMO

Calving ease (CE) is a trait of economic importance that affects animal welfare and farm profitability. The objective of present study was to investigate genetic and environmental factors affecting CE among Primiparous (PP) and multiparous (MP) buffaloes. A total of 9,627 records from 1999 MP and 2,110 PP recorded during the period from 1988 to 2018 were considered. Herd, season of calving, year of calving, birth weight, parity order and gestation length significantly affected CE rate, while age at first calving and sex of calf had no significant effects. Direct and maternal heritabilities of CE in PP and MP were 0.06 and 0.01, respectively. The low heritability of CE indicated that direct selection may not be an effective method to improve CE trait in Egyptian buffalo.


Assuntos
Búfalos/fisiologia , Paridade/fisiologia , Parto/fisiologia , Fatores Etários , Animais , Peso ao Nascer/fisiologia , Cruzamento , Búfalos/genética , Feminino , Masculino , Parto/genética , Gravidez/genética , Gravidez/fisiologia , Estações do Ano
19.
Int J Mol Sci ; 21(21)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158036

RESUMO

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats. We also analyze the modification of these changes by exposure to environmental xenobiotic 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). sncRNA libraries prepared from epididymal spermatozoa were sequenced and analyzed using DESeq 2. The distribution of small RNA fractions changed with age, with fractions mapping to rRNA and lncRNA decreasing and fractions mapping to tRNA and miRNA increasing. In total, 249 miRNA, 908 piRNA and 227 tRNA-derived RNA were differentially expressed (twofold change, false discovery rate (FDR) p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism, while piRNA were enriched for long terminal repeat (LTR) targets. BDE-47 accelerated age-dependent changes in sncRNA in younger animals, decelerated these changes in older animals and increased the variance in expression of all sncRNA. Our results indicate that the natural aging process has profound effects on sperm sncRNA profiles and this effect may be modified by environmental exposure.


Assuntos
Envelhecimento/fisiologia , Exposição Ambiental , Retardadores de Chama/toxicidade , Pequeno RNA não Traduzido/genética , Espermatozoides/metabolismo , Animais , Animais Recém-Nascidos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino , Parto/efeitos dos fármacos , Parto/genética , Parto/metabolismo , Idade Paterna , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Pequeno RNA não Traduzido/metabolismo , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos , Fatores de Tempo
20.
Anim Sci J ; 91(1): e13417, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32662131

RESUMO

The performance of the two-trait animal model that regards the first parity and later parities as two different traits in estimating genetic parameters for number of born alive (NBA) was examined using real and simulated data. Genetic parameters for NBA were estimated in purebred Landrace and Large White pigs using a single-trait repeatability model (Model 1) that regards all parities as the same trait and a two-trait animal model (Model 2) that regards the first and the later parities as different traits. For Model 2, the permanent environmental effect was fitted to only the records of the later parities. Heritability for NBA estimated using Model 1 was 0.12 for Landrace and 0.11 for Large White. Estimated heritability for NBA of the first parity and the later parities was 0.21 and 0.16, respectively, for Landrace; 0.18 and 0.16, respectively, for Large White obtained using Model 2, and higher than those in both breeds obtained using Model 1. Further results based on data simulated using the Monte Carlo method suggest that estimated additive genetic variance could be more biased using Model 2 than Model 1.


Assuntos
Cruzamento/estatística & dados numéricos , Simulação por Computador , Tamanho da Ninhada de Vivíparos/genética , Modelos Animais , Modelos Genéticos , Paridade/genética , Parto/genética , Animais , Feminino , Método de Monte Carlo , Gravidez , Característica Quantitativa Herdável , Suínos
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