威康桑格研究所Roser Vento-Tormo团队取得一项新突破。他们的最新研究提出了发育中的人类生殖道的时空细胞图。相关论文发表在2025年12月17日出版的《自然》杂志上。

在这里，研究团队提出了一个广泛的单细胞和空间多基因组的人类生殖道在产前发育的图谱，以提供超越那些可能的小尺度，器官为主题的研究。通过将组织学特征与基因表达和染色质可及性数据相结合，该研究组定义了可能参与勒氏管和沃尔夫管区域化的转录因子和信号事件。研究团队还细化了HOX编码是如何在不同的生殖器官中建立的，并揭示了胸腔HOX基因的表达在输卵管和附睾的吻侧间质中增加。

他们的研究结果进一步表明，输卵管和附睾的上皮区域化可能在发育过程中建立，这可能有助于精子的成熟和获能。相反，后来的事件是必要的子宫宫颈管上皮区域化。最后，基于单细胞数据和胎儿来源的类器官，该课题组研究人员表明胎儿子宫上皮容易受到雌激素模拟内分泌干扰物的影响。通过在细胞水平上绘制性别特异性生殖道区域化和分化图谱，他们的研究为发育性生殖障碍的主题和潜在治疗提供了有价值的见解。

研究人员表示，人类生殖道对物种延续和整体健康至关重要。它的发育涉及性别规范、组织模式和形态发生的复杂过程，这些过程的破坏可能导致终身问题，包括不孕症。

附：英文原文

Title: Spatiotemporal cellular map of the developing human reproductive tract

Author: Lorenzi, Valentina, Icoresi-Mazzeo, Cecilia, Cassie, Charlotte, Yayon, Nadav, Ruiz-Morales, Elias R., Sancho-Serra, Carmen, Colligan, Ryan, Wong, Frederick C. K., Marekov, Magda, Tuck, Elizabeth, Roberts, Kenny, Li, Tong, Jacques, Marc-Antoine, Ashcroft, James, He, Xiaoling, Crespo, Berta, Cakir, Batuhan, Murray, Simon, Gu, Yong, Predeus, Alexander V., Prete, Martin, Kelava, Iva, Barker, Roger, Garcia-Alonso, Luz, Marioni, John C., Vento-Tormo, Roser

Issue&Volume: 2025-12-17

Abstract: The human reproductive tract is essential for species perpetuation and overall health. Its development involves complex processes of sex specification, tissue patterning and morphogenesis, the disruption of which can cause lifelong issues, including infertility1,2,3,4,5. Here we present an extensive single-cell and spatial multi-omic atlas of the human reproductive tract during prenatal development to provide insights beyond those that are possible with smaller-scale, organ-focused studies. We describe potential regulators of sexual dimorphism in reproductive organs and pinpoint previously unknown genes involved in Müllerian duct emergence and regression and urethral canalization of the penis. By combining histological features with gene expression and chromatin accessibility data, we define transcription factors and signalling events potentially involved in the regionalization of the Müllerian and Wolffian ducts. We also refine how the HOX code is established in distinct reproductive organs and reveal that the expression of thoracic HOX genes is increased in the rostral mesenchyme of the fallopian tube and epididymis. Our findings further indicate that epithelial regionalization of the fallopian tube and epididymis, which probably contribute to sperm maturation and capacitation, is established during development. By contrast, later events are necessary for regionalization of the uterocervical canal epithelium. Finally, on the basis of single-cell data and fetal-derived organoids, we show that the fetal uterine epithelium is vulnerable to oestrogen-mimicking endocrine disruptors. By mapping sex-specific reproductive tract regionalization and differentiation at the cellular level, our study provides valuable insights into causes and potential treatments of developmental reproductive disorders.

DOI: 10.1038/s41586-025-09875-2

Source: https://www.nature.com/articles/s41586-025-09875-2