Toxicology of the male reproductive system has received increased interest in recent years partly fueled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Testicular toxicity (TT) in pharmaceutical development is a challenging issue due to the lack of simple and robust screening methods. Currently, histopathologic examination and hormonal evaluation are the commonly used methods to assess TT. Improved biomarker or screening platforms that would allow identification of TT at an earlier stage can have a significant impact on the safety evaluation of pharmaceutical candidates. We investigated the potential of label-free optical nonlinear imaging technologies such as fluorescence lifetime imaging microscopy (FLIM), multi-photon microscopy (MPM) and coherent anti-Stokes Raman scattering (CARS) microscopy to identify novel biomarkers for effective detection of TT. In this study, testicular damage was induced in rats by intraperitoneal injection with 3 mg/kg cisplatin, a chemotherapy drug. Multimodal optical images were obtained from the fixed, unstained testicular tissue sections of untreated and treated rats using a custom-built near-infrared multiphoton imaging system. Structural and biochemical parameters extracted from these images were compared between both groups to identify abnormal features associated with TT in the treated group. By analyzing the complimentary information obtained using these label-free optical imaging technologies, it may be possible to develop a novel platform for evaluation of TT in safety assessment of pharmaceuticals on reproduction and fertility, which reveal these changes at the molecular level and allow observation of these changes at an earlier time point than available today.
Aneesh Alex, Jang Hyuk Lee, Jose J. Rico-Jimenez, Sunish Mohanan, Stephen A. Boppart, and Zane A. Arp, "Detecting testicular toxicity using label-free multimodal nonlinear optical imaging (Conference Presentation)," Proc. SPIE 10486, Design and Quality for Biomedical Technologies XI, 104860B (Presented at SPIE BiOS: January 27, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2290646.5751448304001.
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