Leptin, an adipocyte-derived hormone, serves numerous physiological functions in the body, particularly during puberty and reproduction. The exact mechanism by which leptin activates the gonadotropin-releasing hormone (GnRH) neurons to trigger puberty and reproduction remains unclear. Given the widespread distribution of leptin receptors in the body, both central and peripheral mechanisms involving the hypothalamic-pituitary-gonadal axis have been hypothesized. Leptin is necessary for normal reproductive function, but when present in excess, it can have detrimental effects on the male reproductive system. Human and animal studies point to leptin as a link between infertility and obesity, a suggestion that is corroborated by findings of low sperm count, increased sperm abnormalities, oxidative stress, and increased leptin levels in obese men. In addition, daily leptin administration to normal-weight rats has been shown to result in similar abnormalities in sperm parameters. The major pathways causing these abnormalities remain unidentified; however, these adverse effects have been attributed to leptin-induced increased oxidative stress because they are prevented by concurrently administering melatonin. Studies on leptin and its impact on sperm function are highly relevant in understanding and managing male infertility, particularly in overweight and obese men.
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.
Infertility is somewhat more prevalent in men who are obese. They are also reported to have low sperm concentration, higher fraction of spermatozoa that look morphologically abnormal, higher DNA fragmentation index and evidence of oxidative stress. The precise cause for this remains uncertain. Leptin levels in serum and percentage body fat correlate positively, and obese men therefore usually have elevated serum leptin levels. Although leptin is important for normal reproductive function, but when present in excess, leptin could seriously affect reproductive function in men. Reports on the findings of sperm parameters in obese men, particularly those who are subfertile or infertile, seem to be similar to those reported from studies on normal-weight rats treated with leptin. Collectively, the observations reported in human and experimental animal studies point to leptin as a possible link between infertility and obesity. Herein, we review some findings on sperm function in obese subfertile or infertile men and those from animal studies following leptin treatment, and discuss the possible link between leptin and reproductive dysfunction in obese men. The large amounts of leptin secreted by the adipose tissue and its higher circulating levels could indeed be responsible for the higher prevalence of infertility in obese men.
Environmental quality indicators are crucial for responsive and cost-effective policies. The objective of the study is to examine the relationship between environmental quality indicators and financial development in Malaysia. For this purpose, the number of environmental quality indicators has been used, i.e., air pollution measured by carbon dioxide emissions, population density per square kilometer of land area, agricultural production measured by cereal production and livestock production, and energy resources considered by energy use and fossil fuel energy consumption, which placed an impact on the financial development of the country. The study used four main financial indicators, i.e., broad money supply (M2), domestic credit provided by the financial sector (DCFS), domestic credit to the private sector (DCPC), and inflation (CPI), which each financial indicator separately estimated with the environmental quality indicators, over a period of 1975-2013. The study used the generalized method of moments (GMM) technique to minimize the simultaneity from the model. The results show that carbon dioxide emissions exert the positive correlation with the M2, DCFC, and DCPC, while there is a negative correlation with the CPI. However, these results have been evaporated from the GMM estimates, where carbon emissions have no significant relationship with any of the four financial indicators in Malaysia. The GMM results show that population density has a negative relationship with the all four financial indicators; however, in case of M2, this relationship is insignificant to explain their result. Cereal production has a positive relationship with the DCPC, while there is a negative relationship with the CPI. Livestock production exerts the positive relationship with the all four financial indicators; however, this relationship with the CPI has a more elastic relationship, while the remaining relationship is less elastic with the three financial indicators in a country. Energy resources comprise energy use and fossil fuel energy consumption, both have distinct results with the financial indicators, as energy demand have a positive and significant relationship with the DCFC, DCPC, and CPI, while fossil fuel energy consumption have a negative relationship with these three financial indicators. The results of the study are of value to both environmentalists and policy makers.