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[CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity and regulates StAR expression in a transgenic mouse
Zhen-Hua Liu1, Jing Xie, Yun-Bei Xiao
1Department of Urology, Peking University People's Hospital, Beijing 100044, China. liuzhenh@126.com
Objective:
To observe the effects of CMTM2 on cyclophosphamide (CP)-induced reproductive toxicity and the expression of steroidogenic acute regulatory (StAR) protein in the transgenic mouse model.
Methods:
Twenty CMTM2 transgenic mice were equally divided into a CMTM2 + CP and a CMTM2 + NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT + CP and a WT + NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and motility by light microscopy and detection of the expression of StAR by Western blot.
Results:
The levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 + CP group as compared with the CMTM2 + NS group ([42.98 +/- 3.25] nmol/L vs [46.74 +/- 3.38] nmol/L, [16.89 +/- 1.17 ] x 10(6)/ml vs [24.68 +/- 0.95 ] x 10(6)/ml, [72.75 +/- 1.25]% vs [85.14 +/- 1.12]%, P < 0.05), but remarkably less than in the WT + CP group ([37.97 +/- 4.17] nmol/L, [12.75 +/- 1.02] x 10(6)/ml, [50.52 +/- 1.37] %) (P < 0.05). However, the expression of StAR was significantly higher in the CMTM2 + CP than in the WT + CP group (1.16 +/- 0.07 vs 0.69 +/- 0.08, P < 0.05).
Conclusion:
CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of StAR, and hence plays a protective role in the reproductive system.
Insights
CMTM2 transgenic mice showed reduced reproductive toxicity from cyclophosphamide (CP) exposure. CMTM2 expression protected against CP-induced damage by regulating steroidogenic acute regulatory (StAR) protein.
Area of Science:
- Reproductive toxicology
- Endocrinology
- Molecular biology
Context:
- Cyclophosphamide (CP) is a known inducer of reproductive toxicity.
- The role of CMTM2 in mitigating CP-induced reproductive damage is not well understood.
- Steroidogenic acute regulatory (StAR) protein is crucial for steroidogenesis.
Purpose:
- To investigate the protective effects of CMTM2 against CP-induced reproductive toxicity.
- To examine the influence of CMTM2 on StAR protein expression in the context of CP exposure.
- To evaluate CMTM2's role in a transgenic mouse model of reproductive toxicity.
Summary:
- CMTM2 transgenic mice and wild-type mice were exposed to CP or saline.
- Reproductive parameters (testosterone, sperm count, motility) and StAR expression were measured.
- CMTM2 transgenic mice exhibited less severe reproductive toxicity and altered StAR expression compared to wild-type mice after CP exposure.
Impact:
- CMTM2 demonstrates a protective role against cyclophosphamide-induced reproductive toxicity.
- The findings suggest CMTM2 antagonizes CP toxicity by modulating StAR protein expression.
- This research provides insights into potential therapeutic targets for reproductive protection.
