Using Sex-reversed Chickens To Identify Core Spermatogenic Regulatory Genes

使用性别逆转鸡来鉴定核心生精调节基因

• 批准号: BB/Y005465/1
• 负责人: Peter Ellis
• 金额: $ 59.07万
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY005465%2F1
• 关键词: Using; Sex; reversed; Chickens; Identify

Over the past decades, due to the protein rich contents of poultry products such as meat and eggs, there has been an exponential increase in commercial chicken production, and it is projected to remain one of the most popular livestock products by volume over the next 10 years. To meet the increasing global demand for poultry products, the production of chickens needs to be constantly expanded, which is dependent on the fertility and reproductive capacity of the male and female (parental) flocks. Commercial poultry management depends on optimal sperm production of relatively few breeding males, and maintaining and enhancing male fertility is a critical factor for large scale production. Selective breeding and restrictive feeding programmes are needed to maintain the fertility and breeding performance of the breeding males. The characteristics that influence the quality of sperm are sperm count, mobility, morphology, and viability, and intact acrosomes. In this research, we aim to understand the molecular network associated with the production of viable gametes by studying spermatogenesis in chickens. In particular, we will make use of a unique model system we have developed to study sperm production in birds with non-typical sex chromosomes. The sex chromosomes are well known to contain master regulators of fertility in many species, and this novel approach will allow us to rapidly identify sex-linked regulators of spermatogenesis.In birds, males have two copies of the Z chromosome and females have one copy each of the Z and W chromosomes. Primordial germ cells (PGCs) are germline-competent cells that give rise to the functional gametes of an animal. It was previously thought that PGCs could only develop into either sperm (if ZZ) or oocytes (if ZW). However, we have recently shown that avian PGCs are bipotent, and can become either sperm or oocyte based on cellular signalling by the surrounding cells within the gonad. When male PGCs (carrying ZZ) are transplanted into a sterile female host (ZW), the ZZ cells form oocytes. Similarly, when female PGCs (ZW) are transplanted into a sterile male host (ZZ), the ZW cells can form functional sperm. Surprisingly, however, after the Z and W chromosomes separate during sperm production only Z-bearing cells survive to contribute to the next generation. We will study these sex-reversed cells in comparison to normal ZZ spermatogenesis, to understand whether the loss of W-bearing sperm in this model system is due to the presence of the W chromosome or the absence of a second Z chromosome. In either case, the findings will highlight key genes that are crucial for regulating cell survival, cell death and fertilizing ability of developing sperm cells. These genes can then be used as targets for selection to improve fertility in roosters.Additionally, we will gather data on the basic biology of spermatogenesis in birds, focusing on two areas that are poorly understood. Firstly, in mammals, the sex chromosomes become inactive (a process known as MSCI, meiotic sex chromosome inactivation) during the meiotic cell stage of spermatogenesis. In chickens, evidence for MSCI is equivocal due to the difficulty accessing oocytes at this stage of development. Our new model is unique in that it allows us to study MSCI during spermatogenesis, where germ cells are much more accessible. Our research will resolve this controversy and offer conclusive evidence for the presence or absence of a sex chromosome transcription silencing mechanism in birds. Secondly, evidence from mammals shows that after the X and Y have been partitioned into separate cells during sperm production, they continue to share gene products (mRNA and protein) across "bridges" between developing cells. This process has however never been studied outside a mammalian context. ZW spermatogenesis offers a unique comparative system to understand the mechanisms and principles underpinning transcript sharing between developing sperm cells.

在过去的几十年里，由于肉和蛋等家禽产品的蛋白质含量丰富，商业鸡肉产量呈指数级增长，预计在未来 10 年仍将是最受欢迎的畜产品之一年。为了满足全球对家禽产品日益增长的需求，需要不断扩大鸡的生产，这取决于雄性和雌性（父母）鸡群的生育力和繁殖能力。商业家禽管理取决于相对较少的繁殖雄性的最佳精子产生，维持和提高雄性生育力是大规模生产的关键因素。需要选择性育种和限制性饲养计划来维持繁殖雄性的生育力和繁殖性能。影响精子质量的特征包括精子数量、活动性、形态和活力以及完整的顶体。在这项研究中，我们的目标是通过研究鸡的精子发生来了解与活配子产生相关的分子网络。特别是，我们将利用我们开发的独特模型系统来研究具有非典型性染色体的鸟类的精子产生。众所周知，许多物种的性染色体含有生育力的主要调节因子，这种新方法将使我们能够快速识别精子发生的性别相关调节因子。在鸟类中，雄性有两份 Z 染色体，雌性各有一份Z 和 W 染色体。原始生殖细胞（PGC）是具有生殖能力的细胞，可产生动物的功能性配子。此前人们认为 PGC 只能发育成精子（如果是 ZZ）或卵母细胞（如果是 ZW）。然而，我们最近发现禽类 PGC 具有双能性，并且可以根据性腺内周围细胞的细胞信号转变成精子或卵母细胞。当雄性 PGC（携带 ZZ）被移植到不育雌性宿主（ZW）中时，ZZ 细胞形成卵母细胞。同样，当雌性 PGC（ZW）被移植到不育的雄性宿主（ZZ）中时，ZW 细胞可以形成有功能的精子。然而，令人惊讶的是，在精子生成过程中 Z 染色体和 W 染色体分离后，只有 Z 染色体细胞能够存活下来，为下一代做出贡献。我们将研究这些性别逆转的细胞，与正常的 ZZ 精子发生进行比较，以了解该模型系统中携带 W 的精子的损失是否是由于 W 染色体的存在或第二条 Z 染色体的缺失。无论哪种情况，研究结果都将突出对调节细胞存活、细胞死亡和发育中精子细胞的受精能力至关重要的关键基因。然后，这些基因可以用作选择的目标，以提高公鸡的生育能力。此外，我们将收集鸟类精子发生的基本生物学数据，重点关注两个知之甚少的领域。首先，在哺乳动物中，性染色体在精子发生的减数分裂细胞阶段变得不活跃（这一过程称为 MSCI，减数分裂性染色体失活）。在鸡中，MSCI 的证据是模棱两可的，因为在这个发育阶段很难获得卵母细胞。我们的新模型的独特之处在于，它使我们能够在精子发生过程中研究 MSCI，此时生殖细胞更容易获得。我们的研究将解决这一争议，并为鸟类中是否存在性染色体转录沉默机制提供确凿的证据。其次，来自哺乳动物的证据表明，在精子产生过程中，X 和 Y 被分成单独的细胞后，它们继续在发育细胞之间的“桥梁”上共享基因产物（mRNA 和蛋白质）。然而，这一过程从未在哺乳动物之外进行过研究。 ZW 精子发生提供了一个独特的比较系统，以了解支持发育中的精子细胞之间转录本共享的机制和原理。