Advances in Anatomy Embryology and Cell Biology最新文献

This chapter provides a cytological and compositional evaluation of the various compartments and sub-compartments making up the bull spermatozoon. The intention is to define the sperm head and tail compartments from an ultrastructural perspective and attribute to them their protein constituents gathered from both traditional and modern proteomic approaches. Common to both approaches, the compositional analysis is dependent on the fractionation and isolation of the sperm compartments combined with polyacrylamide gel electrophoresis (PAGE) and Western blotting to detect the identities of the proteins, and immunocytochemistry to confirm their residency. As will be appreciated, the identity of a particular sperm protein together with its residency provide valuable insights not only into its role, but also to the role of the specific sperm compartment it occupies, in development and/or fertilization. Attention is also given in this chapter to the consequences (on sperm structure and fertility) of inactivating genes that play key roles in sperm formation, especially if their phenotypes appear to match common bull sperm abnormalities. The keywords below cover the sperm head and tail compartments addressed in this chapter.

New and emerging technologies allow for a deeper and more comprehensive understanding of sperm physiology that can be harnessed to improve bull fertility selection. This chapter focuses on (1) the use of conventional and emerging flow cytometry techniques to further enhance functional sperm assessments; (2) new developments in proteomic and metabolomic biomarkers of bull fertility and how they can better inform fertility evaluations; and (3) the use of sperm selection technologies to optimize the fertility outcomes of bulls in artificial insemination service. As our knowledge of sperm physiology continues to expand, technology will allow for a faster translational capacity and continuous development of techniques. The technologies and techniques presented are current tools that can be used to enhance the efficiency, precision and accuracy of bull fertility assessments and better inform herd management.

On completion of spermatogenesis, testicular spermatozoa appear structurally mature but are infertile and must undergo a sequential maturational process in the epididymis to become motile and acquire fertilizing potential. This chapter provides a cell biological overview of the endocytic and secretory activities, along the extratesticular duct system, that provide appropriate conditions for epididymal maturation of bull spermatozoa. The compartmentalization of the bovine epididymis is illustrated and discussed in terms of epithelial cell types and merocrine and apocrine protein secretions by principal cells that influence maturation. Sequential maturational events are followed with examples, first, of testicular proteins associated with spermatozoa that are endocytosed to form a 'clean slate' and then, of epididymal secretory proteins that recondition the sperm milieu and bind to spermatozoa in order to attain its full fertilization potential. Finally, an assessment is made of the potential contributions to epididymal maturation of some well-characterized and identified secretory proteins that interact with the cytoplasmic membrane of spermatozoa.

This chapter examines the role of early life perturbations upon the developing bull calf. Surprisingly, we observe effects upon sexual development and sperm quality, including sperm morphology, as early as the periconception period (-60 to 23 days post conception). Similarly, during postnatal life (prior to 6mths of age) dietary perturbations retard sexual development and sperm quality. Herein we discuss the ontology of development and examine why these periods of development are fundamental to fertility in the bull. Ultimately, this leads to recommendations for changes to current husbandry protocols.

The primary mechanism of telomere elongation in mammals is reverse transcription by telomerase. An alternative (ALT) pathway elongates telomeres by homologous recombination in some cancer cells and during pre-implantation embryo development, when telomere length increases rapidly within a few cell cycles. The maternal and paternal telomeres in the zygote are genetically and epigenetically distinct, with differences in telomere length and in chromatin packaging. We discuss models for how these asymmetries may contribute to telomere regulation during the earliest embryonic cell cycles and suggest directions for future research.

The pancreas has been considered a non-regenerative organ. β cells lost in diabetes are not replaced due to the inability of the pancreas to regenerate. However, ample evidence generated in the last few decades using murine models has demonstrated that the pancreas has a remarkable plasticity wherein differentiated cells can change cell fate toward a β-like cell phenotype. Although this process is observed after using rather artificial stimuli and the conversion efficiency is very limited, these findings have shed some light on novel pathways for β-cell regeneration. In this chapter, we will summarize the different cellular interconversion processes described to date, the experimental details and molecular regulation of such interconversions, and the genomic technologies that have allowed the identification of potential new ways to generate β cells.

The field of epigenetics broadly seeks to define heritable phenotypic modifications that occur within cells without changes to the underlying DNA sequence. These modifications allow for precise control and specificity of function between cell types-ultimately creating complex organ systems that all contain the same DNA but only have access to the genes and sequences necessary for their cell-type-specific functions. The pancreas is an organ that contains varied cellular compartments with functions ranging from highly regulated glucose-stimulated insulin secretion in the β-cell to the pancreatic ductal cells that form a tight epithelial lining for the delivery of digestive enzymes. With diabetes cases on the rise worldwide, understanding the epigenetic mechanisms driving β-cell identity, function, and even disease is particularly valuable. In this chapter, we will discuss the known epigenetic modifications in pancreatic islet cells, how they are deposited, and the environmental and metabolic contributions to epigenetic mechanisms. We will also explore how a deeper understanding of epigenetic effectors can be used as a tool for diabetes therapeutic strategies.

The pancreatic β cells are at the hub of myriad signals to regulate the secretion of an adequate amount of insulin needed to re-establish postprandial euglycemia. The β cell possesses sophisticated metabolic enzymes and a variety of extracellular receptors and channels that amplify insulin secretion in response to autocrine, paracrine, and neurohormonal signals. Considerable research has been undertaken to decipher the mechanisms regulating insulin secretion. While the triggering pathway induced by glucose is needed to initiate the exocytosis process, multiple other stimuli modulate the insulin secretion response. This chapter will discuss the recent advances in understanding the role of the diverse glucose- and fatty acid-metabolic coupling factors in amplifying insulin secretion. It will also highlight the intracellular events linking the extracellular receptors and channels to insulin secretion amplification. Understanding these mechanisms provides new insights into learning more about the etiology of β-cell failure and paves the way for developing new therapeutic strategies for type 2 diabetes.

Successful reproduction relies on the union of a single chromosomally normal egg and sperm. Chromosomally normal eggs develop from precursor cells, called oocytes, that have undergone accurate chromosome segregation. The process of chromosome segregation is governed by the oocyte spindle, a unique cytoskeletal machine that splits chromatin content of the meiotically dividing oocyte. The oocyte spindle develops and functions in an idiosyncratic process, which is vulnerable to genetic variation in spindle-associated proteins. Human genetic variants in several spindle-associated proteins are associated with poor clinical fertility outcomes, suggesting that heritable etiologies for oocyte dysfunction leading to infertility exist and that the spindle is a crux for female fertility. This chapter examines the mammalian oocyte spindle through the lens of human genetic variation, covering the genes TUBB8, TACC3, CEP120, AURKA, AURKC, AURKB, BUB1B, and CDC20. Specifically, it explores how patient-identified variants perturb spindle development and function, and it links these molecular changes in the oocyte to their cognate clinical consequences, such as oocyte maturation arrest, elevated egg aneuploidy, primary ovarian insufficiency, and recurrent pregnancy loss. This discussion demonstrates that small genetic errors in oocyte meiosis can result in remarkably far-ranging embryonic consequences, and thus reveals the importance of the oocyte's fine machinery in sustaining life.