**5.3 Red palm oil in male infertility prevention**

As shown in the previous section in this chapter, RPO is rich in antioxidants such as carotenoids, vitamin E derivatives, and ubiquinone and should thus be a good candidate to prevent male infertility. Though, scientific literature on the effect of RPO on male reproduction is scarce.

Overall, a direct effect of RPO on spermatogenesis is inconclusive. Some in vivo studies reported poor sperm functions and morphology after exposure to RPO, whereas other noticed no significant effects. However, many studies demonstrated that RPO can protect against or ameliorate toxin- or medical condition-induced male infertility. Aboua et al. [59] showed that long-term RPO supplementation to rats had no effect on enzymes activities or substrates involved in the antioxidant defense system (GSH, CAT, SOD), lipid peroxidation or intracellular ROS levels in spermatozoa. Similarly, RPO exposure did not significantly change concentration or motility of spermatozoa. RPO did, however, significantly lower or even prevent ROS-induced changes to peroxide-injected animals. Peroxide alone led to lipid membrane peroxidation and higher intracellular ROS levels and consequently significantly lowered sperm concentration and motility and reduced enzyme activities. But peroxide exposure in combination with RPO prevented these changes and thus protected the sperm from ROS-induced damage [59]. In a similar approach Jegede et al. [60] demonstrated that RPO can attenuate heavy metal induced testicular damage in rats. Here, the administration of lead acetate led to a significant rise in reactive oxygen species that in turn decreased GSH concentrations and led to reduced spermatozoa numbers and motility and an increase in abnormal sperm morphology. Coadministration of RPO was able to partially protect against these changes as shown by significantly increased GSH levels and improved spermatozoa parameters. Peroxide in higher concentration induces DNA breaks and programmed cell death (apoptosis) in spermatozoa which consequently leads to lower sperm counts and reduces male fertility [61]. Aboua et al. [15] demonstrated that a 60-day oral supplementation of RPO can prevent peroxide-induced apoptosis in rat spermatozoa. Here, RPO supplementation prevented the activation of caspases 3 and 7 and, therefore, apoptosis. In addition, RPO seems to reduce the activation of p53 which will also lessen apoptosis.

As stated before, obesity can lead to diabetes type 2 which is known to impair male fertility by inter alia reducing sperm quality [53]. In diabetic rats RPO supplementation was shown to elevate the percentage of progressive motile spermatozoa [9]. The authors further demonstrated that RPO in combination with an aqueous extract from fermented rooibos exerted no negative effect on sperm motility parameters as measured by Computer Assisted Sperm Analysis but improved these parameters in diabetic rats. There is a significant linear relationship between abdominal obesity and prostate cancer [62]. Treatment of prostate cancer often involves radiation therapy or surgery that will remove the prostate and the seminal vesicles. Both options greatly impair the production of semen and thus often led to male infertility. RPO can lower the unpleasant effects of chemotherapy and is thus used in cancer management [63]. However, RPO or more precisely, a tocotrienol-rich fraction (TRF) from RPO may have potential as a remedy for prostate cancer. Using three different prostate cancer cell lines [64] noticed that TRF selectively inhibited cell proliferation and induced apoptosis in these cells.

As shown above, the antioxidative capacity of RPO can help to reduce or even prevent ROS-induced damage to the male germ cell. On the other hand, a certain physiological amount of ROS activity is essential for spermatogenesis and normal sperm functions. Thus, excessive use of antioxidants can have a negative effect on spermatogenesis and male fertility [65, 66]. This might be the reason as to why Aboua et al. [67] noted a significant decline in the motility of spermatozoa in vitro after exposure to RPO. A more recent in vivo study investigated the effects of a specific high-fat diet on the male rat reproductive performances. Male Wistar rats were fed either with a 15% palm oil diet or a standard diet for 16 weeks. The authors concluded that the palm oil significantly impaired sexual behavior, ejaculatory activities and sperm motility, viability, and morphology of male rats [68]. Overall, a precisely tuned balance between ROS level needed for physiological sperm function and sufficient antioxidants to combat oxidative cellular damage is vital for male fertility.
