Sex determination and differentiation are complex and delicate processes. In female chickens, the process of sex differentiation is sensitive and prone to be affected by the administration of aromatase inhibitors, which result in chicken sex reversal and infertility. However, the molecular mechanisms underlying sex differentiation and infertility in chicken sex reversal remain unclear. Therefore, we established a sex-reversed chicken flock by injecting an aromatase inhibitor, fadrozole, and constructed relatively high-resolution profiles of the gene expression and chromatin accessibility of embryonic gonads. We revealed that fadrozole affected the transcriptional activities of several genes, such as DMRT1, SOX9, FOXL2, and CYP19A1, related to sex determination and differentiation, and the expression of a set of gonadal development-related genes, such as FGFR3 and TOX3, by regulating nearby open chromatin regions in sex-reversed chicken embryos. After sexual maturity, the sex-reversed chickens were confirmed to be infertile, and the possible causes of this infertility were further investigated. We found that the structure of the gonads and sperm were greatly deformed, and we identified several promising genes related to spermatogenesis and infertility, such as SPEF2, DNAI1, and TACR3, through RNA-seq. This study provides clear insights into the exploration of potential molecular basis underlying sex differentiation and infertility in sex-reversed chickens and lays a foundation for further research into the sex development of birds.

中文翻译：

---

ATAC-seq 和 RNA-seq 分析揭示了性反转鸡性别分化和不育的机制

性别决定和分化是复杂而微妙的过程。雌性鸡的性别分化过程敏感，易受芳香化酶抑制剂的影响，导致鸡性逆转和不育。然而，鸡性逆转导致性别分化和不育的分子机制仍不清楚。因此，我们通过注射芳香化酶抑制剂法卓唑建立了性反转鸡群，并构建了相对高分辨率的胚胎性​​腺基因表达和染色质可及性图谱。我们发现法卓唑影响了与性别决定和分化相关的几个基因的转录活性，例如 DMRT1、SOX9、FOXL2 和 CYP19A1，以及一组性腺发育相关基因的表达，例如 FGFR3 和 TOX3，通过调节性反转鸡胚胎中附近的开放染色质区域。性成熟后，确认性反转鸡不育，进一步调查不育的可能原因。我们发现性腺和精子的结构发生了很大的变形，我们通过 RNA-seq 鉴定了几个与精子发生和不育相关的有前途的基因，如 SPEF2、DNAI1 和 TACR3。该研究为探索性反转鸡性别分化和不育的潜在分子基础提供了清晰的见解，为进一步研究鸟类的性别发育奠定了基础。性反转鸡被证实不育，进一步调查不育的可能原因。我们发现性腺和精子的结构发生了很大的变形，我们通过 RNA-seq 鉴定了几个与精子发生和不育相关的有前途的基因，如 SPEF2、DNAI1 和 TACR3。该研究为探索性反转鸡性别分化和不育的潜在分子基础提供了清晰的见解，为进一步研究鸟类的性别发育奠定了基础。性反转鸡被证实不育，进一步调查不育的可能原因。我们发现性腺和精子的结构发生了很大的变形，我们通过 RNA-seq 鉴定了几个与精子发生和不育相关的有前途的基因，如 SPEF2、DNAI1 和 TACR3。该研究为探索性反转鸡性别分化和不育的潜在分子基础提供了清晰的见解，为进一步研究鸟类的性别发育奠定了基础。通过 RNA-seq。该研究为探索性反转鸡性别分化和不育的潜在分子基础提供了清晰的见解，为进一步研究鸟类的性别发育奠定了基础。通过 RNA-seq。该研究为探索性反转鸡性别分化和不育的潜在分子基础提供了清晰的见解，为进一步研究鸟类的性别发育奠定了基础。