Evaluation of the efficacy of creatine chemical exchange saturation transfer imaging in assessing testicular maturity

Author:

Kuribayashi Sohei1ORCID,Fukuhara Shinichiro1,Tsujimura Go1,Imanaka Takahiro1,Okada Koichi1,Ueda Norichika1,Takezawa Kentaro1,Kiuchi Hiroshi1,Saito Shigeyoshi23,Takahashi Yusuke45,Kioka Hidetaka4,Oura Seiya6,Shimada Keisuke6ORCID,Ikawa Masahito67ORCID,Nonomura Norio1

Affiliation:

1. Department of Urology Osaka University Graduate School of Medicine Suita Japan

2. Department of Medical Physics and Engineering, Division of Health Sciences Osaka University Graduate School of Medicine Suita Japan

3. Department of Advanced Medical Technologies National Cerebral and Cardiovascular Research Center Suita Japan

4. Department of Cardiovascular Medicine Osaka University Graduate School of Medicine Suita Japan

5. Department of Molecular Pharmacology National Cerebral and Cardiovascular Center Research Institute Suita Japan

6. Research Institute for Microbial Diseases Osaka University Suita Japan

7. Graduate School of Pharmaceutical Sciences Osaka University Suita Japan

Abstract

AbstractPurposeMicroscopic testicular sperm extraction is the most effective treatment for NOA, but the sperm retrieval rate is low and depends on testicular maturity. However, there are limited useful tests to assess testicular maturity. Chemical exchange saturation transfer (CEST) imaging is a new magnetic resonance imaging (MRI) technique that can image the distribution of trace substances in vivo. We focused on the potential role of creatine (Cr) in testes and hypothesized that Cr‐CEST could indicate intratesticular spermatogenesis.MethodsWe performed Cr‐CEST by using 7T MRI on wild‐type C57B6/J mice and several types of male infertility models such as Sertoli‐cell only (SCO) (Kitw/Kitwv), maturation arrest (MA) (Zfp541 knockout mouse and Kctd19 knockout mouse), and teratozoospermia (Tbc1d21 knockout mouse). After performing Cr‐CEST, histological analysis was performed.ResultsThe SCO and MA models showed decreased CEST signal intensity (p < 0.05), while no reduction was observed in the teratozoospermia model (p = 1.0). CEST signal intensity increased as the spermatogenesis stage progressed from the SCO model to the MA and teratozoospermia models. Furthermore, CEST signal intensity was reduced in 4‐week‐old wild‐type mice with immature testes (p < 0.05).ConclusionsThis study suggests that Cr‐CEST evaluates intratesticular spermatogenesis noninvasively and provides a new therapeutic strategy for treating male infertility.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Cell Biology,Reproductive Medicine

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