| Obsjective:Evidences have shown a causality link between male obesity and subfertility or infertility. The underlying mechanism, however, is incompletely understood. Here we report for the first time that sustained high protein-tyrosine phosphatase1B (PTP1B) activity plays an essential role in coupling male obesity and subfertility or infertility.Method:Obesity and healthy mice and human sperm samples by progesterone-induced acrosome reaction,Western blot analysis detected expression levels of PTP1B, Co-immunoprecipitation assay PTP1B activity, discuss impact of obesity on the expression levels of PTP1B; Chlortetracycline fluorescence (CTC) assay and in vitro fertilization (IVF) detect acrosome reaction rate, discuss obesity on acrosome function; Western blot analysis detected the expression P-NSF, VAMP2expression level, Indirect immunofluorescence and double labeling fluorescent assay VAMP2expression levels of PTP1B expression level discussion on the sperm acrosome function.Result:First, PTP1B level and activity was significantly higher in sperms from ob/ob mice than that from wild-type littermates. High PTPIB level and activity in sperms was also observed in obese patient compared to non-obese donors. The enhanced sperm PTPIB level and activity in ob/ob mice and obese patients correlated with the defect of sperm acrosome reaction (AR). Second, treating sperms from male ob/ob mice or obese men with specific PTP1B inhibitor largely restored the sperm AR. Finally, blockade of sperm AR by enhanced PTPIB activity in male ob/ob mice and obese men was due to prolonged dephosphorylation of N-ethylmaleimide-sensitive factor by PTPIB, leading to failure to reassembly the trans-SNARE complexes, a critical step of sperm acrosomal exocytosis.Conclusion:In summary, our study demonstrates that sustained high PTPIB level or activity in sperms of obese donors can cause defect of sperm AR and that PTP1B may be a novel therapeutic target of male infertility treatment. |
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