Liu Hui, Gong Yuneng, Qu Xiaoyan, Cui Sheng, Zhang Di
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.
Institute of Reproduction and Metabolism, Yangzhou University, Jiangsu, People's Republic of China.
PLoS One. 2025 Aug 18;20(8):e0329503. doi: 10.1371/journal.pone.0329503. eCollection 2025.
Uterine glands and their secretions are essential for conceptus survival and development, with abnormalities in uterine gland morphogenesis (adenogenesis) are closely related to high rates of peri-implantation embryonic loss in humans and livestock. While uterine adenogenesis occurs postnatally in most mammals, the key regulatory factors and mechanisms governing this developmental event remains largely unexplored. Our recent study reveals that cysteine dioxygenase (CDO) is highly expressed in the uterus of adult mice, which is also rich in taurine. Notably, Cdo knockout (KO) and the resulting taurine deficiency lead to the defects in embryo implantation and subfertility. However, the regulatory roles of CDO and taurine in uterine development and adenogenesis remain unclear. In the current study, we assayed CDO expression and taurine content in the developmental uteri of mice from postnatal day (PND) 3 to PND 28, and investigated the regulatory roles of CDO and taurine in uterine adenogenesis using Cdo KO mice. Our results showed that uterine CDO protein expression gradually increased from PND 3 to prepuberty, closely correlating with uterine taurine levels. Cdo KO and taurine deficiency impaired the formation and development of uterine gland by inhibiting uterine epithelial cell proliferation and enhancing cell apoptosis. Remarkably, taurine supplementation partially rescued these defects in uterine adenogenesis. These findings, for the first time, demonstrate that uterine tissue acquires the ability to synthesis taurine postnatally, CDO and taurine act as novel factors regulating uterine gland development. Uncovering the mechanisms of uterine adenogenesis could significantly improve pregnancy outcomes in humans and other mammals.
子宫腺体及其分泌物对胚胎的存活和发育至关重要，子宫腺体形态发生（腺发生）异常与人类和家畜着床前后胚胎高丢失率密切相关。虽然大多数哺乳动物的子宫腺发生在出生后发生，但控制这一发育事件的关键调节因子和机制在很大程度上仍未被探索。我们最近的研究表明，半胱氨酸双加氧酶（CDO）在成年小鼠子宫中高度表达，子宫中也富含牛磺酸。值得注意的是，Cdo基因敲除（KO）以及由此导致的牛磺酸缺乏会导致胚胎着床缺陷和生育力低下。然而，CDO和牛磺酸在子宫发育和腺发生中的调节作用仍不清楚。在本研究中，我们检测了出生后第3天（PND）至PND 28天小鼠发育子宫中CDO的表达和牛磺酸含量，并使用Cdo基因敲除小鼠研究了CDO和牛磺酸在子宫腺发生中的调节作用。我们的结果表明，子宫CDO蛋白表达从PND 3到青春期前逐渐增加，与子宫牛磺酸水平密切相关。Cdo基因敲除和牛磺酸缺乏通过抑制子宫上皮细胞增殖和增强细胞凋亡，损害了子宫腺体的形成和发育。值得注意的是，补充牛磺酸部分挽救了这些子宫腺发生缺陷。这些发现首次证明子宫组织在出生后获得了合成牛磺酸的能力，CDO和牛磺酸作为调节子宫腺体发育的新因子。揭示子宫腺发生的机制可以显著改善人类和其他哺乳动物的妊娠结局。
