Department of Obstetrics, Gynecology & Reproductive Biology, Michigan State University, College of Human Medicine, Grand Rapids, MI, USA.
Cell and Molecular Biology Program, Michigan State University, College of Natural Science, East Lansing, MI, USA.
Reprod Sci. 2022 Oct;29(10):2947-2959. doi: 10.1007/s43032-022-00980-5. Epub 2022 May 31.
Endometriosis is a condition of the female reproductive tract characterized by endometrium-like tissue growing outside the uterus. Though it is a common cause of pelvic pain and infertility, there is currently no reliable noninvasive method to diagnose the presence of endometriosis without surgery, and the pathophysiological mechanisms that lead to the occurrence of symptoms require further inquiry. Due to patient heterogeneity and delayed diagnosis, animal models are commonly used to study the development of endometriosis, but these are costly due to the large number of animals needed to test various treatments and experimental conditions at multiple endpoints. Here, we describe a method for synthesis of multimodal imaging gold-fluorescein isothiocyanate (FITC) nanoparticles with preclinical application via induction of nanoparticle-labeled endometriosis-like lesions in mice. Labeling donor endometrial tissue fragments with gold-FITC nanoparticles prior to induction of endometriosis in recipients enables in vivo detection of the gold-labeled lesions with photoacoustic imaging. The same imaging method can be used to visualize embryos noninvasively in pregnant mice. Furthermore, the conjugated FITC dye on the gold nanoparticles allows easy isolation of labeled lesion tissue under a fluorescence dissection microscope. After dissection, the presence of gold-FITC nanoparticles and endometrium-like histology of lesions can be verified through fluorescence imaging, gold enhancement, and immunostaining. This method for in vivo imaging of endometriosis-like lesions and fluorescence-guided dissection will permit new experimental possibilities for the longitudinal study of endometriosis development and progression as well as endometriosis-related infertility.
子宫内膜异位症是一种女性生殖系统疾病,其特征是子宫内膜样组织在子宫外生长。尽管它是导致盆腔疼痛和不孕的常见原因,但目前尚无可靠的非侵入性方法在不进行手术的情况下诊断子宫内膜异位症的存在,并且导致症状发生的病理生理机制需要进一步研究。由于患者的异质性和诊断延迟,通常使用动物模型来研究子宫内膜异位症的发展,但由于需要大量动物来测试各种治疗方法和实验条件的多个终点,因此这些模型成本高昂。在这里,我们描述了一种通过诱导小鼠体内纳米粒子标记的子宫内膜异位样病变来合成多模态成像金-荧光素异硫氰酸酯(FITC)纳米粒子的方法,该方法具有临床前应用价值。在接受者中诱导子宫内膜异位症之前,用金-FITC 纳米粒子标记供体子宫内膜组织片段,可使金标记的病变在体内通过光声成像进行检测。相同的成像方法可用于在怀孕的小鼠中无创地可视化胚胎。此外,金纳米粒子上的共轭 FITC 染料可允许在荧光解剖显微镜下轻松分离标记的病变组织。解剖后,通过荧光成像、金增强和免疫染色可验证金-FITC 纳米粒子的存在以及病变的子宫内膜样组织学。这种用于子宫内膜异位样病变的体内成像和荧光引导解剖的方法将为子宫内膜异位症发展和进展以及与子宫内膜异位症相关的不孕的纵向研究提供新的实验可能性。