Heavy Metal Toxicosis and Male Fertility: The Role of Pentahydroxyflavone Quercetin: a Review

The effect of heavy metals (HMs) has been extensively studied. They cause diverse clinical manifestation through various mechanisms. Male fertility is among the most disturbing effect of HMs affecting family life in human and reproduction in animals. Notably among these effects is interference with the reproductive hormones, morphology and function of reproductive organs, sexual behaviors, and the spermiogram. Quercetin is a dietary flavanoid from edible plants and, has proven pharmacological properties in the treatment and management of many disease conditions. Quercetin ameliorates the adverse effects of HMs on male reproductive hormones by increasing the activity of 3β-hydroxysteroid dehydrogenase (3β- HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) in the synthesis of testosterone. Quercetin chelates HMs, scavenge free radicals, and other cytotoxicant capable of disrupting the morphology and function of the male reproductive system. Apart from it neuroprotective activity on the pituitary gland and increased steroidogenesis, quercetin mitigate neurotransmitter that aid in copulation and improve histopathological changes in the brain due to HMs toxicity to improve sexual behavior. Quercetin was also found to be effective in increasing sperm count, daily sperm production, mortility, viability, and also decreased in the percentage of abnormal sperm morphology due to HMs toxicity. In conclusion quercetin was found to be effective in mitigating HMs toxicity that affects male fertility, and so, it is recommended to be incorporated into the treatment and management of HMs toxicity. Individuals who are at risk of HMs toxicity should take dietary plants that contain quercetin to minimize the effects of these metals.

Circadian effects of ionizing radiation on reproductive function and clock genes expression in male mouse

Background Exposure to the ionizing radiation (IR) encountered outside the magnetic field of the Earth poses a persistent threat to the reproductive functions of astronauts. The potential effects of space IR on the circadian rhythms of male reproductive functions have not been well characterized so far. Methods Here, we investigated the circadian effects of IR exposure (3 Gy X-rays) on reproductive functional markers in mouse testicular tissue and epididymis at regular intervals over a 24-h day. For each animal, epididymis was tested for sperm motility, and the testis tissue was used for daily sperm production (DSP), testosterone levels, and activities of testicular enzymes (glucose-6-phosphate dehydrogenase (G6PDH), sorbitol dehydrogenase (SDH), lactic dehydrogenase (LDH), and acid phosphatase (ACP)), and the clock genes mRNA expression such as Clock, Bmal1, Ror-α, Ror-β, or Ror-γ. Results Mice exposed to IR exhibited a disruption in circadian rhythms of reproductive markers, as indicated by decreased sperm motility, increased daily sperm production (DSP), and reduced activities of testis enzymes such as G6PDH, SDH, LDH, and ACP. Moreover, IR exposure also decreased mRNA expression of five clock genes (Clock, Bmal1, Ror-α, Ror-β, or Ror-γ) in testis, with alteration in the rhythm parameters. Conclusion These findings suggested potential health effects of IR exposure on reproductive functions of male astronauts, in terms of both the daily overall level as well as the circadian rhythmicity.

Interleukin-6 deficiency modulates testicular function by increasing the expression of suppressor of cytokine signaling 3 (SOCS3) in mice

Several cytokines have been reported to participate in spermatogenesis, including interleukin-6 (IL6). However, not many studies have been conducted on the loss of Il6 on the male reproductive tract. Nonetheless, there is considerable knowledge regarding the pathological and physiological role of IL6 on spermatogenesis. In this way, this study evaluated the impact of Il6 deficiency on mice testicles in the absence of infection or inflammation. We showed that Il6 deficiency increases daily sperm production, the number of spermatids, and the testicular testosterone and dihydrotestosterone levels. Besides that, mice with a deleted Il6 (IL6KO) showed increased testicular SOCS3 levels, with no changes in pJAK/JAK and pSTAT3/STAT3 ratios. It is worth noting that the aforementioned pathway is not the only pathway to up-regulate SOCS3, nor is it the only SOCS3 target, thus proposing that the increase of SOCS3 in the testis occurs independently of the JAK-STAT signaling in IL6KO mice. Therefore, we suggest that the lack of Il6 drives androgenic production by increasing SOCS3 in the testis, thus leading to an increase in spermatogenesis.

Testis structure, duration of spermatogenesis and daily sperm production in four wild cricetid rodent species (A. cursor, A. montensis, N. lasiurus, and O. nigripes)

Although rodents represent approximately 40% of all living mammalian species, our knowledge regarding their reproductive biology is still scarce. Due to their high vulnerability to environmental changes, wild rodents have become beneficial models for ecological studies. Thus, we aimed to comparatively investigate key functional testis parameters in four sexually mature wild rodent species (A. cursor, A. montensis, N. lasiurus, and O. nigripes). These species belong to the Cricetidae family, which is the most diverse family of rodents in South America, with a total of ~120 species in Brazil. The results found for the gonadosomatic index and the sickled sperm head shape observed strongly suggest that the species here evaluated are promiscuous, prolific, and short-lived. The duration of spermatogenesis was relatively short and varied from ~35–40 days. Both the percentage of seminiferous tubules (ST) in the testis parenchyma (~95–97%) and the number of Sertoli cells (SC) (~48–70 million) per testis gram were very high, whereas a fairly good SC efficiency (~8–13 round spermatids per SC) was observed. In comparison to other mammalian species studied, particularly the rodents of the suborder Myomorpha (i.e. hamsters, rats and mice), the rodents herein investigated exhibited very high (~62–80 million) daily sperm production per testis gram. This impressive spermatogenic efficiency resulted mainly from the short duration of spermatogenesis and quite high values found for the ST percentage in the testis and the SC number per testis gram. We expect that the knowledge here obtained will help conservation programs and the proper management of wildlife.

Low Doses of Glyphosate/Roundup Alter Blood–Testis Barrier Integrity in Juvenile Rats

It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.

Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

Background The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. Methods Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. Results Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. Conclusion These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

GONADAL AND EXTRAGONADAL SPERM RESERVES AND TESTICULAR HISTOMETRY OF POST PUBERTAL MUTURU BULLS.

Testes and epididymides were obtained from three pubertial Muturu bulls aged 11 months and 12 post pubertal bulls aged between 13 and 17 months and weighed between 91 and 148kg. Samples of each testis and epididymal segments namely, caput, corpus and cauda, were processed for histology while samples for gonadal and extragonadal sperm reserves were processed using the homogenisation technique. Paired testes weight increased from 78.99+8.74g at 11months of age to 90.10+10.86g. 110.30+5.67g and 106.34-6.52g at 13, 15 and 17 months of age, respectively. Paired testes sperm numbers were 3.00+1.50 X 10', 5.25 0.51 x 10', 10.44+2.55 x 10° and 9.14+3.08 x 10°, during the corresponding periods. Similarly, daily sperm production (DSP) increased by 77%, 250% and 207% at 13, 15 and 17 months of age, respectively. There was a 22% increase in the seminiferous tubule diameter from the time of puberty at 11 months to the time bulls were 15 months old, but the histological characteristics of the different epididymal segments did not follow any definite trend during these periods. Correlations between paired testes weight and other testicular and epididymal parameters were positive and significant (P<0.01). These results suggest that Muturu bulls may be used for breeding from the age of 15 months.

SPERM PRODUCTION RATES OF EUROPEAN BOARS RAISED AND MAINTAINED IN THE HUMID TROPICS WITH A NOTE ON SORBITOL DEHYDROGENASE ACTIVITY AS AN INDEX OF SPERMATOGENESIS

Paired tests weight of twelve adult Large White boars (x = 18.5months)ranged from 424.90g to 705.90g while volumen percent of round spermatid nuclei in the testes was 3.63 ± 0.16. Mean daily sperm production and daily sperm production per gram testicular parenchyma were respectively 19.47 ± 0.78 x 109 and 33.47 ± 1.29 x 106 . In the second study the sorbitol dehydrogenase activity per gram deproteinised testicular parenchyma was negatively and not significantly correlated (r = 0.2)with the daily sperm produced per gram testis parenchyma

The effect of Kapok (Ceiba pentandra) (Linn] [Gaertn] meal on sperm production rate, gonadal and extragonadal sperm reserves in male rabbits

Twenty grower male rabbits of mixed breeds were used to evaluate the effect of Kapok seed meal on sperm production and sperm storage capacity: Five bucks each were randomly assigned to each of four isocaloric and isonitrogenous diets containing decorticated Kapok seed meal at 0), 10, 15 und 20% levels. After 8 weeks of ad libitum feeding, four bucks per treatment were randomly selected from each treatment group, sacrificed and their testes evaluated for sperm production, the efficiency of spermatogenesis and sperm storage capacity. The results did not show any significant differences (P>0.05) between the treatments in Daily sperm production (DSP), Daily sperm production/ gram testis (DSP/g) as well as in gonadal and extragonadal sperm reserves. These results suggest that decorticated Kapok seed meal had no significant effect on sperm production in breeding bucks at an inclusion level of up to 20%. KSM may thus be a useful source of protein for rabbit bucks.

Sperm production rate, gonadal and extragonadal sperm reserves in slaughtered White Fulani (Bunaji) bulls in a lowland tropical environment

Reproductive tract morphometry, sperm production rates, gonadal and extragonadal sperm reserves in Bunaji bulls were evaluated using samples from a total of 13 mature animals. The morphometric characteristics of the reproductive organs had generally low values but showed normal development. The daily sperm production (DSP) averaged 1.23 ± 0.16 x 109, while the daily sperm production (DSG/g) was 0.62 ± 0.11 x 107. Gonadal sperm reserve was 2.17 ± 0.73 x 109 while extragonadal sperm reserve was 3.82 x 109 for caput, 2.68 x 109 for corpus, 4.36 x 10 (for cauda epididymis and 0.62 x 109 for the ductus deferens. The relative contributions of the epididymal segments and the ductus deferns to the total extragonadal sperm reserves were 33.28%, 23.34%, 37.98% and 5.40% respectively. Testicular morphomeric characteristics correlated highly with themselves and with sperm production parameters as well as extragonadal sperm reserve. While these results provided information that would be useful in the determination if male/female ratio during mating and artificial insemination programmmes, the study also shows that good sires could be obtained from these animals for breeding and improvement programmes in this breed.