Using sex-reversed chickens to identify core spermatogenic regulatory genes

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Chickens are the most abundant livestock animal because of their efficient growth and food conversion, cultural acceptability as a food source, and nutritional products, which are a vital source of protein for humans. Every year, on average, 73 billion chickens are slaughtered for their meat. Researchers are implementing innovative technology to enhance production of poultry products in response to this increasing demand. This project will study a unique sex-reversed model of spermatogenesis in order to identify sex-linked regulators of avian fertility. Primordial germ cells (PGCs) are germline stem cells that are widely used for biobanking chicken breeds and to produce genetically modified birds. In birds, males are homogametic (ZZ sex chromosomes) while females are heterogametic (ZW). Early stage PGCs have a sex specific transcriptome and proteome i.e. ZZ and ZW cells are intrinsically different. Despite this, however, we have shown that avian PGCs are bipotent, and in transplant experiments can be induced to form either sperm or oocytes dependent on the sex of the host embryo. In particular, female PGCs (ZW) survive through meiosis and divide to form sperm when transplanted into a sterile male host, but only the Z-bearing sperm survive. This offers a unique opportunity to use sex-reversed ZW spermatogenesis as a model system to identify master Z-borne regulators of fertility, while also addressing fundamental biological questions. In birds, meiotic sex chromosome silencing (MSCI) is a debatable topic where evidence is equivocal due to the difficulty in accessing chicken oocytes. ZW spermatogenesis provides a unique platform to investigate MSCI in a more accessible system. We hypothesize that MSCI is either incomplete or absent in birds; otherwise silencing of the Z would lead to spermatocyte death during or prior to meiosis. Instead, we believe W-bearing sperm die due to incomplete sharing of Z- and W-borne transcripts between sister spermatids following meiosis.