Edouard Akono Nantia

Adverse Effects of Bisphenol A on Male Reproductive Function

BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the overall BPA effects on male reproduction appear to be more harmful if exposure occurs in utero. The regulation of BPA and BPA-related products should be reinforced, particularly where exposure during the fetal period can occur. The current TDI for BPA is proposed as 25 and 50 1-1g/kg bwt/day (European Food Safety Authority and Health Canada, respectively). Based on the evidence available, we believe that a TDI value of 5 1-1g/kg bwt/day is more appropriate (the endpoint is modulation of rat testicular function). Certain BPA derivatives are being considered as alternatives to BPA. However, certain of these related products display adverse effects that are similar to those of BPA. These effects should be carefully considered before using them as final alternatives to BPA in plastic production.

Effect of agropesticides use on male reproductive function: A study on farmers in Djutitsa (Cameroon)

This study aimed at investigating the effect of agropesticides on male reproductive function in farmers in Djutitsa (West Cameroon). To this end, 47 farmers in Djutitsa were asked questions on their health status and pesticide use in agriculture. Thereafter, their blood samples were collected for assessment of sex hormones including serum luteinizing hormone (LH), follicle‐stimulating hormone (FSH), androstenedione, testosterone, as well as sex hormone binding globulin (SHBG). Their serum triiodothyronine (T3) and thyroxine (T4) levels were also measured. Thirty seven men not exposed to agropesticides were recruited as control group. Fifty six pesticides containing 25 active substances were currently used by farmers enrolled in our study, and most of their symptoms were related to spread/use of these chemicals. Compared to the control group, there was no significant difference in FSH, LH, SHBG, estradiol, and thyroid hormones (T3 and T4) levels. Farmers had significantly lower serum testosterone (20.93 ± 1.03 nM vs. 24.32 ± 1.32 nM; P < 0.05) and higher androstenedione level (3.83 ± 0.20 nM vs. 2.80 ± 0.15 nM; P < 0.001). Their serum free testosterone as well as bioavailable testosterone were unchanged, while estradiol/testosterone and androstenedione/testosterone ratios were significantly increased (0.45 ± 0.03% vs. 0.33 ± 0.02%; P < 0.01 and 12.26 ± 3.64 vs 19.31 ± 6.82; P < 0.001, respectively). Our results suggest that male farmers of Djutitsa (West Cameroon) are exposed to agropesticides due to improper protective tool, and this exposure may impair their reproductive function through inhibition of testosterone synthesis; probably by inhibition of testicular 17β‐ hydroxysteroid dehydrogenase (17HSD3) and induction of aromatase (CYP19).

Effect of Environmental Contaminants on Mammalian Testis

Exposure of humans and wildlife to pollutants released in the environment is a centre of attention nowadays. Many of these chemicals (generally referred to as environmental pollutants) have been shown to interfere with normal hormonal signalling and biological functions, leading to reproductive disorders or infertility, which has been a matter of concern within the recent decades. The present paper reviews adverse effects of these toxicants on mammalian testes, with emphasis on alteration of steroidogenesis, spermatogenesis, and histopathological effects. From the publications reviewed, it appears that environmental toxicants, especially heavy metals and organic chemicals of synthetic and microbiological origins, disrupt hormone production and action in the mammalian testes. Endocrine disruption leads to disorders of testicular function and thereby compromises the normal phenotypic development of male sexual characteristics, initiation and maintenance of spermatogenesis. The toxicants also induce impairment of testicular cells function, testicular histology, and sperm cells function directly. The release of the toxicants in the environment is still ongoing, despite alarming quantities that already exist in the atmosphere. If appropriate measures are not taken, their impact on the male reproductive function and especially on testicular function will be more serious.

QuEChERS-based method for the determination of carbamate residues in aromatic herbs by UHPLC-MS/MS

A new reliable, fast and highly sensitive method based on ultra-high performance liquid chromatography tandem mass spectrometry has been developed and validated for the determination of 28 carbamates in aromatic herbs. A modified QuEChERS-based method was optimized for the extraction of carbamate residues from a wide variety of fresh herbal products. The proposed method allowed recoveries higher than 72%, achieving quantification limits of 2μgkg(-1), therefore below maximum residue limits established for this type of samples. The combination of QuEChERS with UHPLC-MS/MS introduces a high-throughput methodology for the monitoring of these residues in this type of matrices scarcely explored. The analysis of the real samples revealed that several samples sold in the European Union and in the North West region of Cameroon contain pesticides in concentrations below the maximum residue limits.

Effects of the Methanol Extract of Basella alba L (Basellaceae) on Steroid Production in Leydig Cells

In this study, Leydig cells were purified from 70 day-old Sprague Dawley male rats and incubated with 10 and 100 μg/mL of methanol extract of Basella alba (MEBa) for 4 hours followed by the evaluation of cell viability, steroid (testosterone and estradiol) production, and the level of aromatase mRNA. Results showed that MEBa did not affect Leydig cell viability. At the concentration of 10 μg/mL, MEBa significantly stimulated testosterone and estradiol production (p < 0.01 and p < 0.03, respectively), and enhanced aromatase mRNA level (p < 0.04). These observations suggest that MEBa directly stimulated testosterone, estradiol and aromatase mRNA levels in isolated Leydig cells.

Etude de l’effet androgénique de l’extrait au méthanol deBasella alba L. (Basellaceae) sur la fonction de reproduction du rat mâle

ResumeBasellaalba est une plante utilisée par les tradipraticiens de la province de l’Ouest Cameroun pour lutter contre l’asthénie sexuelle et l’infertilité chez l’homme. Les travaux antérieursin vitro ont prouvé l’activité androgénique de son extrait au méthanol. Le présent travail porte sur la confirmationin vivo de son effet androgénique chez le rat mâle adulte. Cet extrait est quotidiennement administré (par gavage) pendant 30 jours aux doses de 0, 0,1, 1, 10 et 100 mg/kg respectivement à 5 groupes de 6 rats mâles.Les animaux sont pesés tous les deux jours et au terme de 30 jours de traitement sont sacrifiés. Le sang est recueilli; le foie et les organes de reproduction (testicules, épididymes, vésicules séminales, prostate) prélevés et pesés. Le sang est utilisé pour le dosage de la testostérone du sérum par125I-RIA et de quelques marqueurs de toxicité du foie et des reins. D’autres indicateurs de l’intégrité cellulaire sont également estimés dans le foie.Les résultats montrent que l’extrait au méthanol deB. alba n’a pas d’effet sur le poids corporel des animaux ainsi que sur celui des organes de reproduction. Après 30 jours de traitement, l’effet de l’extrait au méthanol deB. alba sur la production de testostérone est significativement élevé (p<0,0005) à la dose 1 mg/kg, alors qu’à partir de 10 mg/kg d’extrait, ce niveau de testostérone baisse, mais reste élevé par rapport au témoin. Toujours au niveau du sérum, le taux de créatinine et l’activité de l’alanine aminotransférase ne montrent pas de variation significative entre les animaux témoins et ceux traités aux différentes doses d’extrait.Cette observation est identique quant aux paramètres mésurés dans le foie: aniline hydroxylase, taux de protéines, de glutathion, d’aldéhyde malonique.Ces résultats suggèrent que l’extrait au méthanol deB. alba a une activité androgéniquein vivo qui est maximale à la dose 1 mg/kg de poids corporel.AbstractBasella alba is a plant used by some herbalists of the West province of Cameroon to enhance male virility and fertility. Previousin vitro studies have shown the androgenic activity of its methanol extract. This study therefore focused on confirmation of the androgenic activity of the methanol extract ofB. alba in vivo in male rats. A suspension of this extract in corn starch was administered daily to 5 groups of rats at doses of 0,0.1, 1, 10 and 100 mg/kg respectively for 30 days. The animals were weighed every second day during this period.On the 31st day of the experiment, the animals were sacrificed and blood was collected for serum assays. The liver and reproductive organs (testes, epididymides, seminal vesicles and prostates) were also collected and weighed. Serum testosterone level was determined by radio-immunoassay (125I-RIA) techniques, and various markers of liver and kidney toxicity (alanine aminotransferase and creatinine) were also assayed. Liver post-mitochondrial supernatant was used to estimate other markers of cell integrity, such as malondialdehyde, glutathione, and aniline hydroxylase activity.The results showed that the methanol extract ofB. alba has no effect on the weight of the animal and reproductive organs compared to the control. After 30 days of treatment, serum testosterone levels were significantly increased (p<0.0005) up to the dose of 1 mg/kg, but decreased at higher dosages of the extract, although remained higher than that of controls. Aniline hydroxylase and aminotransferase activities, malondialdehyde, protein, glutathione and creatinine levels were not significantly altered by administration of the methanol extract ofB. alba.These results suggest that the methanol extract ofB. alba has anin vivo androgenic activity with a maximum effect at the dose of 1 mg/kg body weight.

Protective effect of Basella alba and Carpolobia alba extracts against maneb-induced male infertility.

Abstract Context: Male infertility is one of the leading causes of social frustration and marginalization, mainly in the developing world. It is attributed to many factors including exposure to agropesticides such as manganese ethylenebis (dithiocarbamate) (maneb), which is one of the most frequently used fungicides in Cameroon. Previous reports support efficiency of some medicinal plants commonly used in Cameroonian folk medicine for the treatment of this disorder. Objective: The present study was aimed at assessing the protective effect of extracts from selected plant species, namely Basella alba L. (Basellaceae) (MEBa) and Carpolobia alba G. Don (Polygalaceae) (AECa), in alleviating the maneb-induced impairment of male reproductive function in Wistar albino rats. Materials and methods: The rats were treated with vehicle, plant extract (MEBa or AECa), maneb and maneb plus plant extract, respectively, and their fertility was assessed. Animals were thereafter sacrificed and organs (liver, kidneys and reproductive organs) were dissected out and weighed. Serum androgens together with alanine aminotransferase, liver glutathione and thiobarbituric acid reactive species (TBARS) were also measured. Results and discussion: From this study, both plant extracts stimulated testosterone and improved fertility. Administration of MEBa plus maneb prevented fertility reduction by maneb and minimized the inhibitory effect of maneb on testosterone levels. AECa also improved fertility of the maneb-exposed rats, though without restoring testosterone levels, and other investigated parameters remained unaffected by different treatments. Conclusion: These findings emphasized the beneficial effects of B. alba and C. alba extracts on male fertility, and suggest their protective effect against maneb-induced toxicity in male reproductive function.

Effect of methanol extract of Basella alba L. (Basellaceae) on the fecundity and testosterone level in male rats exposed to flutamide in utero

We evaluated the effect of the methanol extract of Basella alba (MEBa) on testosterone level and fecundity/fertility in male rats exposed in utero to flutamide – an androgen receptor antagonist. For this purpose, 1.5‐ and 2.5 ‐month‐old male rats exposed in utero to flutamide were treated with the MEBa (1 mg kg−1) for 2 and 1 month respectively. Five days before the end of treatment, rats were housed with females to assess their fecundity/fertility. Thereafter, rats were sacrificed and blood collected for the quantification of testosterone. Flutamide‐exposed male rats showed a decrease in their ano‐genital distance (AGD, P < 0.05) and were infertile. In normal (methylcellulose‐exposed) animals, MEBa provoked an increase in testosterone level in 1.5‐ (P < 0.008) and 2.5 ‐month‐old rats (P < 0.01) concomitantly with the improvement in their fecundity by 25%. In flutamide‐exposed male rats, MEBa increased testosterone level in 1.5 ‐month‐old rats (P < 0.001) without any effect on their fecundity; while in 2.5‐ month‐old rats, MEBa did not affect the testosterone level but improved fecundity (by 25%) and fertility (P < 0.001). This study demonstrated the positive effect of MEBa to enhance fecundity/fertility in normal male rats and in rats exposed to the antiandrogen flutamide during their foetal life.

Hepatotoxicity and Hepatoprotective Effects of African Medicinal Plants

Liver diseases constitute a global concern, and available medical treatments have limited efficacy. Herbal medicines have been used for treatment of aliments since ancient times, and some plant extracts and natural compounds find applications as hepatoprotective active principles, while others adversely induced liver toxicity used for treatment of diseases unrelated to liver. Indeed, the liver represents the key “metabolic factory” in the organism and, therefore the most exposed organ to xenobiotics, and may be modulated by any compound irrespective to the purpose of use. This chapter reviews the modulatory effect of African medicinal plants on liver. We identified 47 medicinal plants, with 36 and 11 plants exhibiting hepatoprotective and hepatotoxic effect, respectively. The action mechanisms involved in the hepatotoxicity/hepoprotection by the identified plants are not well elucidated, though modulation of antioxidant system is emphasized. More in-depth research studies are needed to clarify the pathways and molecules involved in their action, and to investigate other unstudied medicinal plants, in order to guarantee their safe use.

Evaluation of the effect of Carpolobia alba (Polygalaceae) aqueous extract on male reproductive function in rats

In order to assess the effect of Carpolobia alba on male reproductive function, its aqueous extract was tested on lactate release by rat Sertoli cell cultures. The extract was administered daily to adult male rats. After 60 days of treatment, the animals were sacrificed and weight of organs (liver, kidneys, testes, epididymides, seminal vesicles and prostate) recorded. Liver glutathione levels and aniline hydroxylase activity, epididymal α-glycosidase activity, as well as serum testosterone level and aminotransferase activities were also assessed. Carpolobia alba extract at the doses 0.01 and 0.1 mg/kg significantly increased serum testosterone levels (P<0.01) in male rats, while other investigated parameters on serum and Sertoli cells remained unchanged. These results proved the androgenic effect of C. alba and thereby, sustain its use in the management of male infertility.