scholarly journals PSVII-41 Late-Breaking Abstract: Impact of enhanced early life nutrition on the testes transcriptional profile of the bull calf

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 341-342
Author(s):  
Stephen P Coen ◽  
David A Kenny ◽  
Sean Fair ◽  
Pat Lonergan ◽  
Kate Keogh
Keyword(s):  
Sexual Development ◽  
Molecular Mechanisms ◽  
System Development ◽  
Cholesterol Biosynthesis ◽  
Reproductive Function ◽  
Seminiferous Tubules ◽  
Bull Calf ◽  
Luteinizing Hormones ◽  
Bull Calves ◽  
Signaling Axis

Abstract Enhanced plane of nutrition and metabolic status are known to progress sexual development in the bull calf. This is facilitated through neuroendocrine signaling in the hypothalamic-pituitary-testicular signaling axis. Improved nutrition may lead to early release of hypothalamic gonadotropin releasing hormone (GnRH) and the subsequent production of follicle stimulating luteinizing hormones in the anterior pituitary and ultimately development of the testes and sexual development. Nonetheless the precise molecular mechanisms leading to this effect are yet to be expounded. The purpose of this study was to evaluate differentially expressed (DE) genes within the testes of bull calves differentially fed for the first 12 weeks of life. The main functions of the testes are the biosynthesis of androgens by the leydig cells and sperm production by the seminiferous tubules. Accelerating the development of this tissue may lead to enhanced reproductive development at an earlier stage. Holstein Friesian bull calves with a mean (SEM) age and bodyweight of 17.5 (2.8) days and 48.8 (5.3) kg, respectively, were assigned to either a high (H; n = 15) or moderate (M; n = 15) plane of nutrition, to achieve an average target growth rate of 1.0 and 0.5 kg/day, respectively. Calves on H and M received 1.5 and 0.5 kg of milk replacer (MR) per day, reconstituted at 15 and 12.5% (w/v), respectively. Calves on H were offered concentrate ad libitum, while those on M received, 500g day-1. Both groups were offered 500 g of hay daily. At 87 days (±2.141) of age, all calves were euthanized and the testes recovered from all calves. RNA was isolated from all testes samples and subsequently subjected to RNAseq analysis. Calves offered a higher plane of nutrition were heavier at slaughter (112 v 88 kg, P < 0.001), reflective of their higher ADG (0.88 v 0.58 kg, P < 0.001). Similarly, H also had heavier testes (29.2 v 20.1 g, P < 0.05) compared to M calves. Results from RNAseq analysis identified 27 DE genes (p.adj< 0.1; fold change >1.5). Cholesterol biosynthesis was an enriched pathway and reproductive system development was also affected. We also saw that Claudin11 was an up regulated DE gene which is involved in sertoli cell development. The results from this study would advocate that there is potential effects of improved nutrition on reproductive function within the testes of bull calves at 12 weeks of age.

scholarly journals Prebiotics mannan-oligosaccharides accelerate sexual maturity in rats: A randomized preclinical study

2021 ◽  
pp. 1210-1219
Author(s):  
Luiz Eduardo Rodrigues ◽  
Milena Miyoshi Kishibe ◽  
Rogeria Keller ◽  
Heliard Rodrigues dos Santos Caetano ◽  
Marcos Natal Rufino ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
System Development ◽  
Reproductive Function ◽  
Experimental Period ◽  
Preclinical Study ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Male Reproductive Function ◽  
Moment Interaction ◽  
Mannan Oligosaccharides

Background and Aim: The prebiotics, mannan-oligosaccharides (MOS), demonstrate the ability to increase probiotic microorganisms and fixation and removal of pathogens associated with chronic systemic inflammation in the digestive system. Inflammatory processes play an important role in modulating the brain-intestinal axis, including maintaining male reproductive function and spermatogenesis and regulating stress. The aim of the present study was to evaluate the action of MOS on testosterone and corticosterone concentrations and the reproductive system development of rats in the growth phase as an animal model. Materials and Methods: In total, 128 male rats were used, randomly divided into four experimental groups (n=32): Control; MOS 1; MOS 2; and MOS 3. From each group, eight animals were sacrificed in four experimental moments (14, 28, 42, and 56 days, respectively, moments 1, 2, 3, and 4) and hormonal measurements and histological evaluations were performed. Results: The results revealed the effect of diet, MOS, and timing on testicle weight (p<0.05). At moments 3 and 4, the groups supplemented with MOS showed higher concentrations of testosterone and decreased corticosterone levels throughout the experimental period. Groups supplemented with MOS showed an increase in the frequency of relative sperm and sperm scores. The radii of the seminiferous tubules presented a significant statistical effect of the diet, moments, and diet + moment interaction. Conclusion: It was concluded that the three different MOS prebiotics brought forward sexual maturity.

scholarly journals PSIX-26 Effect of enhanced nutrition during early life on the transcriptional profile of the arcuate nucleus region of the hypothalamus in Holstein Friesian bull calves

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 332-333
Author(s):  
Kate Keogh ◽  
Stephen P Coen ◽  
Pat Lonergan ◽  
Sean Fair ◽  
David A Kenny
Keyword(s):  
Early Life ◽  
Molecular Mechanisms ◽  
Arcuate Nucleus ◽  
High Energy ◽  
Testicular Development ◽  
Bull Calf ◽  
Bull Calves ◽  
Holstein Friesian ◽  
Hypothalamic Function ◽  
Hpt Axis

Abstract Improved nutrition and metabolic status during early life are known to advance sexual development in the bull calf. This is mediated through complex neuroendocrine signaling at the level of the hypothalamic-pituitary-testicular (HPT) axis resulting in precocious testicular development and spermatogenesis. The arcuate nucleus region (ARC) of the hypothalamus is centrally involved in the integration of peripheral metabolic cues with GnRH neuronal function and gonadotropin pulsatility which in turn stimulate testicular development. However, the precise molecular mechanisms regulating the influence of prevailing nutritional status on hypothalamic function are yet to be fully elucidated. The objective of this study was to evaluate differentially expressed genes (DEG) within the ARC of bull calves offered contrasting planes of nutrition during the first 12 weeks of life, to coincide with the characteristic transient gonadotropin rise. Holstein-Friesian bull calves with a mean (+SD) bodyweight and age of 48.8(5.3) kg and 17.5(2.8) days, respectively, were assigned to either a high energy (H; n = 15) or moderate energy (M; n = 15) plane of nutrition designed for growth rates of 1.0 and 0.5 kg/day, respectively. At 12 weeks of age all calves were euthanized and the ARC harvested. RNA was isolated from all ARC samples and RNAseq analysis conducted. As expected, H calves were heavier at euthanasia (H=112 kg; M=88 kg, P &lt; 0.001). RNAseq analysis resulted in the identification of 83 DEG (P.adj&lt; 0.1; fold change &gt;1.5), all of which were down-regulated in H compared to M calves. DEG were enriched for biological pathways associated with immune function including complement system and acute phase response signaling (P.adj&lt; 0.01). However, no DEG identified were directly involved in reproductive developmental processes. Results from this study suggest that the typically positive effect of enhanced nutrition on reproductive development may not be apparent within the ARC at 12 weeks of age.

scholarly journals Zebrafish Models of Autosomal Recessive Ataxias

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 836
Author(s):  
Ana Quelle-Regaldie ◽  
Daniel Sobrido-Cameán ◽  
Antón Barreiro-Iglesias ◽  
María Jesús Sobrido ◽  
Laura Sánchez
Keyword(s):  
Animal Models ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
System Development ◽  
Rapid Development ◽  
Nervous System Development ◽  
Central Nervous System Development ◽  
Cellular Processes ◽  
Recessive Disorders

Autosomal recessive ataxias are much less well studied than autosomal dominant ataxias and there are no clearly defined systems to classify them. Autosomal recessive ataxias, which are characterized by neuronal and multisystemic features, have significant overlapping symptoms with other complex multisystemic recessive disorders. The generation of animal models of neurodegenerative disorders increases our knowledge of their cellular and molecular mechanisms and helps in the search for new therapies. Among animal models, the zebrafish, which shares 70% of its genome with humans, offer the advantages of being small in size and demonstrating rapid development, making them optimal for high throughput drug and genetic screening. Furthermore, embryo and larval transparency allows to visualize cellular processes and central nervous system development in vivo. In this review, we discuss the contributions of zebrafish models to the study of autosomal recessive ataxias characteristic phenotypes, behavior, and gene function, in addition to commenting on possible treatments found in these models. Most of the zebrafish models generated to date recapitulate the main features of recessive ataxias.

scholarly journals Comparative Transcriptome Analysis Reveals Sex-Based Differences during the Development of the Adult Parasitic Wasp Cotesia vestalis (Hymenoptera: Braconidae)

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 896
Author(s):  
Yuenan Zhou ◽  
Pei Yang ◽  
Shuang Xie ◽  
Min Shi ◽  
Jianhua Huang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Adult Development ◽  
Sexual Development ◽  
Molecular Mechanisms ◽  
Parasitic Wasp ◽  
Differentially Expressed Gene ◽  
Regulation Mechanism ◽  
Rna Seq ◽  
Male And Female ◽  
Cotesia Vestalis

The endoparasitic wasp Cotesia vestalis is an important biological agent for controlling the population of Plutella xylostella, a major pest of cruciferous crops worldwide. Though the genome of C. vestalis has recently been reported, molecular mechanisms associated with sexual development have not been comprehensively studied. Here, we combined PacBio Iso-Seq and Illumina RNA-Seq to perform genome-wide profiling of pharate adult and adult development of male and female C. vestalis. Taking advantage of Iso-Seq full-length reads, we identified 14,466 novel transcripts as well as 8770 lncRNAs, with many lncRNAs showing a sex- and stage-specific expression pattern. The differentially expressed gene (DEG) analyses showed 2125 stage-specific and 326 sex-specific expressed genes. We also found that 4819 genes showed 11,856 alternative splicing events through combining the Iso-Seq and RNA-Seq data. The results of comparative analyses showed that most genes were alternatively spliced across developmental stages, and alternative splicing (AS) events were more prevalent in females than in males. Furthermore, we identified six sex-determining genes in this parasitic wasp and verified their sex-specific alternative splicing profiles. Specifically, the characterization of feminizer and doublesex splicing between male and female implies a conserved regulation mechanism of sexual development in parasitic wasps.

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

scholarly journals erbB-1 and erbB-4 Receptors Act in Concert to Facilitate Female Sexual Development and Mature Reproductive Function

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1465-1472 ◽  
Author(s):  
Vincent Prevot ◽  
Alejandro Lomniczi ◽  
Gabriel Corfas ◽  
Sergio R. Ojeda
Keyword(s):  
Glial Cells ◽  
Sexual Development ◽  
Double Mutant ◽  
Reproductive Function ◽  
Receptor Activation ◽  
Dominant Negative ◽  
Reproductive Capacity ◽  
Erbb Receptor ◽  
Signaling Systems ◽  
Lhrh Release

Glial erbB-1 and erbB-4 receptors are key components of the process by which neuroendocrine glial cells control LHRH secretion and the onset of female puberty. We now provide evidence that these two signaling systems work in a coordinated fashion to control reproductive function. To generate animals carrying functionally impaired erbB-1 and erbB-4 receptors, we crossed Waved 2 (Wa-2+/+) mice harboring a point mutation of the erbB-1 receptor with mice expressing a dominant-negative erbB-4 receptor in astrocytes. In comparison to single-deficient mice, double-mutant animals exhibited a further delay in the onset of puberty and a strikingly diminished adult reproductive capacity. Ligand-dependent erbB receptor phosphorylation and erbB-mediated MAPK (ERK 1/2) phosphorylation were impaired in mutant astrocytes. Wa-2+/+ or double-mutant astrocytes failed to respond to TGFα with production of prostaglandin E2, one of the factors mediating the stimulatory effect of astroglial erbB receptor activation on LHRH release. Medium conditioned by Wa-2+/+ or double-mutant astrocytes treated with TGFα failed to stimulate LHRH release from GT1–7 cells. The LH response to ovariectomy was significantly attenuated in mutant mice in comparison with wild-type controls. Although the Wa-2 mutation affects all cells bearing erbB-1 receptors, these results suggest that a major defect underlying the reproductive defects of animals with impaired erbB signaling is a decreased ability of glial cells to stimulate LHRH release. Thus, a coordinated involvement of erbB-1 and erbB-4 signaling systems is required for the normalcy of sexual development and the maintenance of mature female reproductive function.

Molecules from the Microbiome

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Emilee E. Shine ◽  
Jason M. Crawford
Keyword(s):  
Small Molecules ◽  
Molecular Mechanisms ◽  
System Development ◽  
Human Microbiome ◽  
Host Responses ◽  
Annual Review ◽  
Publication Date ◽  
Mechanistic Studies ◽  
Immune System Development ◽  
Interdisciplinary Approaches

The human microbiome encodes a second genome that dwarfs the genetic capacity of the host. Microbiota-derived small molecules can directly target human cells and their receptors or indirectly modulate host responses through functional interactions with other microbes in their ecological niche. Their biochemical complexity has profound implications for nutrition, immune system development, disease progression, and drug metabolism, as well as the variation in these processes that exists between individuals. While the species composition of the human microbiome has been deeply explored, detailed mechanistic studies linking specific microbial molecules to host phenotypes are still nascent. In this review, we discuss challenges in decoding these interaction networks, which require interdisciplinary approaches that combine chemical biology, microbiology, immunology, genetics, analytical chemistry, bioinformatics, and synthetic biology. We highlight important classes of microbiota-derived small molecules and notable examples. An understanding of these molecular mechanisms is central to realizing the potential of precision microbiome editing in health, disease, and therapeutic responses. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1703-1709 ◽  
Author(s):  
T. Furuchi ◽  
K. Masuko ◽  
Y. Nishimune ◽  
M. Obinata ◽  
Y. Matsui
Keyword(s):  
Transgenic Mice ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Elongation Factor ◽  
Chain Elongation ◽  
Seminiferous Tubules ◽  
Testicular Germ Cell ◽  
Abnormal Accumulation ◽  
Normal Spermatogenesis ◽  
Massive Accumulation

During normal spermatogenesis, more than half of the germ cells undergo apoptosis, but the physiological significance and molecular mechanisms of this programmed cell death are largely unknown. Because Bcl-2 functions as a death repressor, we have investigated the effect of misexpressing Bcl-2 in spermatogonia in transgenic mice using the human bcl-2 cDNA under the control of the human polypeptide chain elongation factor 1alpha (EF-1alpha) promoter. In the 2-week-old transgenic testes, exogenous Bcl-2 was expressed in spermatogonia and massive accumulation of spermatogonia was observed in seminiferous tubules by 4 weeks. At this time, only a few spermatocytes were apparent, and the accumulated cells degenerated, leading to vacuolization in some seminiferous tubules by 7 weeks. In older transgenic mice, abnormal accumulation of spermatogonia and degeneration of these germ cells was still observed, but some seminiferous tubules in which the level of Bcl-2 expression was reduced recovered normal spermatogenesis. These observations indicate that spermatogonial apoptosis is part of the normal program of mammalian spermatogenesis and is regulated by a pathway affected by Bcl-2.

scholarly journals Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications

Medicines ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 82 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Intraepithelial Neoplasia ◽  
Cancer Development ◽  
Initial Development ◽  
Therapeutic Implications ◽  
Cancer Pathways ◽  
Signaling Axis ◽  
Prostate Cancer Development ◽  
Prostate Cancers

Prostate cancer is the most frequent nonskin cancer and second most common cause of cancer-related deaths in man. Prostate cancer is a clinically heterogeneous disease with many patients exhibiting an aggressive disease with progression, metastasis, and other patients showing an indolent disease with low tendency to progression. Three stages of development of human prostate tumors have been identified: intraepithelial neoplasia, adenocarcinoma androgen-dependent, and adenocarcinoma androgen-independent or castration-resistant. Advances in molecular technologies have provided a very rapid progress in our understanding of the genomic events responsible for the initial development and progression of prostate cancer. These studies have shown that prostate cancer genome displays a relatively low mutation rate compared with other cancers and few chromosomal loss or gains. The ensemble of these molecular studies has led to suggest the existence of two main molecular groups of prostate cancers: one characterized by the presence of ERG rearrangements (~50% of prostate cancers harbor recurrent gene fusions involving ETS transcription factors, fusing the 5′ untranslated region of the androgen-regulated gene TMPRSS2 to nearly the coding sequence of the ETS family transcription factor ERG) and features of chemoplexy (complex gene rearrangements developing from a coordinated and simultaneous molecular event), and a second one characterized by the absence of ERG rearrangements and by the frequent mutations in the E3 ubiquitin ligase adapter SPOP and/or deletion of CDH1, a chromatin remodeling factor, and interchromosomal rearrangements and SPOP mutations are early events during prostate cancer development. During disease progression, genomic and epigenomic abnormalities accrued and converged on prostate cancer pathways, leading to a highly heterogeneous transcriptomic landscape, characterized by a hyperactive androgen receptor signaling axis.

Gene Trap, Gene Knockout, Gene Knock-In, and Transgenics in Vascular Development

1999 ◽  
Vol 82 (08) ◽  
pp. 865-869 ◽  
Author(s):  
Thomas Sato
Keyword(s):  
Animal Models ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
System Development ◽  
Gene Knockout ◽  
Vascular Development ◽  
Branching Morphogenesis ◽  
Abnormal Development ◽  
Organ Systems ◽  
Almost All

IntroductionThe vascular system is one of the first organ systems to develop in our bodies. Normal development and maturation of the physiological functions of almost all of the other organs are critically dependent on the accurate and tightly controlled establishment of the vascular system. Our understanding of the mechanisms underlying the formation of the vascular system during development is still in its infancy. With further understanding of these mechanisms, we may eventually be able to correct the abnormal development and the malfunctioning of many organs by therapeutically modulating the morphology and/or physiological function of the vascular system.Our further understanding of the vascular development can, in part, be achieved by discovering the molecules that play critical roles in this process. We could also achieve this goal by learning more about the functions of previously identified molecules in the vascular system. Discovery of new processes underlying the development of the vascular system will also contribute to further understanding of these molecular mechanisms.Recent advances, using the whole genome approach, have resulted in a flood of new information. This trend will continue, and fortunately, a number of molecular reagents will become available. Therefore, the field will likely experience an exponential growth in terms of novel biological insights and discovering the mechanisms of vascular system development.Occasionally, reductionistic approaches help to systematically address a number of biological problems, including the problems associated with vascular system development. One such approach is to choose an organism that allows us to systematically address these biological questions. The choice of animal models that are well-suited for the study of a particular question has led to a large number of discoveries. To address questions in vascular system development, current research has focused on animal models, including fish, frog, bird, and mouse, and also studies involving humans. It is also worthwhile to note that the branching morphogenesis of the fly trachea system has been utilized to address fundamental questions of vascular morphogenesis.This chapter will summarize the genomic manipulation of the murine vascular system to address questions regarding vascular development. In addition, the advances that have been made in this field using such methods will be summarized.

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