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LY294002, a PI3K pathway inhibitor, prevents leptin‐induced adverse effects on spermatozoa in Sprague‐Dawley rats
Author(s) -
Md Mokhtar Amir Hafidz,
Malik Ifrah Alam,
Abd Aziz Noor Azean Anis,
Almabhouh Fayez A.,
Durairajanayagam Damayanthi,
Singh Harbindar Jeet
Publication year - 2019
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.13196
Subject(s) - ly294002 , leptin , adverse effect , endocrinology , medicine , pi3k/akt/mtor pathway , andrology , chemistry , pharmacology , biology , microbiology and biotechnology , signal transduction , obesity
This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin‐induced adverse effects on rat spermatozoa. Sprague‐Dawley rats, aged 14–16 weeks, were randomised into control, leptin‐, leptin + dorsomorphin (AMPK inhibitor)‐, and leptin+LY294002 (PI3K inhibitor)‐treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg −1 body weight. Rats in the leptin and inhibitor‐treated groups received concurrently either dorsomorphin (5 mg kg −1 day −1 ) or LY294002 (1.2 mg kg −1 day −1 ) i.p. for 14 days. Controls received 0.1 ml of normal saline. Upon completion, sperm count, sperm morphology, seminiferous tubular epithelial height (STEH), seminiferous tubular diameter (STD), 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) and phospho‐Akt/total Akt ratio were estimated. Data were analysed using ANOVA. Sperm count, STEH and STD were significantly lower, while the percentage of spermatozoa with abnormal morphology and the level of 8‐OHdG were significantly higher in rats treated with leptin and leptin + dorsomorphin when compared to those in controls and LY294002‐treated rats. Testicular phospho‐Akt/total Akt ratio was significantly higher in leptin and leptin + LY294002‐treated rats. In conclusion, LY294002 prevents leptin‐induced changes in rat sperm parameters, suggesting the potential role of the PI3K signalling pathway in the adverse effects of leptin on sperm parameters.