Reproductive toxicological effects of gossypol on male rabbits: semen characteristics and hormonal levels

Abstract

The objective of this study was to evaluate the effects of two sublethal doses (4 and 20 mg/kg live weight (LW); every other day) of gossypol on semen and hormonal characteristics of male rabbits. The experiment lasted 16 weeks and included two periods: a treatment period (first 8 weeks) where the animals were given the test materials, and a recovery period (second 8 weeks) where drugs were withdrawn. Results showed that LW and respiration rate (RR) decreased ( P , 0·05) among animals that received gossypol, while rectal temperature increased ( P , 0·05). Animals in gossypol treatment groups had decreased ( P , 0·05) blood plasma levels of tri-iodothyronine (T 3 ) and testosterone. This was accompanied by reductions ( P , 0·05) in sperm concentration, total sperm output, percentage incidence of forward motility, total functional sperm fraction and semen initial fructose concentration. Gossypol however increased ( P , 0·05) reaction time (i.e. decreased libido), percentages of dead sperm and abnormal sperm (AbSp) and altered acrosomes. Estimated weights of testes and semen ejaculate volume increased ( P , 0·05) possibly due to increased water retention. Values of LW, RR, AbSp, and blood plasma T 3 and testosterone returned to control levels after withdrawal of gossypol, while the effect of this drug on other parameters continued during the recovery period.

Molecular approach of gossypol-induced reproductive toxicity in male rabbits. Changes in seminal plasma amino acids and fatty acids

“…This agrees with the present results in which the concentrations of these amino acids were reduced by treatment with gossypol in a dose-dependent manner (Table 1), which was accompanied by severe reduction in sperm concentration (Taha et al, 2006).…”

“…Our studies on the same rabbits showed that this gossypol-induced reduction of seminal amino acids was associated with poor-quality semen, i.e. low concentration, low motility, and increase in dead and abnormal sperm (Taha et al, 2006). This finding coincided with those of Hopwood and Gassner (1962) who reported that increased concentration of seminal total free amino acids was related to the increased quality and fertility of semen, and that poor semen quality was related to amino acids imbalance.…”

“…In addition, bovine spermatozoa were found to have functional mechanism for the active transport of glycine, which is enhanced at low hexose concentration (Dietz and Flipse, 1966). Thus, a gossypol-induced reduction in fructose concentration, which we observed previously (Taha et al, 2006), may indirectly enhance glycine uptake by spermatozoa. Furthermore, using the male contraceptive RISUG TM was noted to induce sperm membrane rupture, which was associated with significant decreases in seminal plasma concentrations of isoleucine, leucine and alanine (Chaudhury et al, 2002).…”

“…Gossypol was extracted from cottonseeds and purified according to Boatner (1948) as described by Taha et al (2006). Gossypol was firstly dissolved in acetone then in corn oil to give a concentration of 20 mg/ml; this mixture was freshly prepared on the day of dosing.…”

“…On the other hand, oleic and linoleic acids were reported to be vulnerable to free radicals and reactive oxygen species and are easily peroxidized (Ouchi et al, 2002). Additionally, gossypol-induced hypothyroidism (Taha et al, 2006) acts synergistically to enhance cell apoptosis, where hypothyroidism leads to a decrease in oleic acid (Saha et al, 1998). Collectively, these findings could support and explain our previous observations, showing that gossypol administration was followed by a reduction in sperm quality and quantity (Taha et al, 2006), which could be considered as a sign of cell apoptosis.…”