L’impact de l’utilisation des agropesticides sur la fonction de reproduction mâle est évalué chez des agriculteurs de Djutitsa (Ouest Cameroun). Le pesticide le plus utilisé par ces agriculteurs est testé in vivo sur la fonction de reproduction du rat mâle, ex vivo et/ou in vitro sur la stéroïdogenèse Leydigienne afin d’évaluer son implication dans les déséquilibres observés chez les agriculteurs. Ensuite, l’effet protecteur des extraits de Carpolobia alba et Basella alba contre les effets délétères dudit pesticide est évalué in vivo chez des rats mâles, ainsi que leur influence sur la production de la protéine de transport des stéroïdes (SHBG) par les cellules HepG2. Les résultats montrent que les agriculteurs utilisent 25 agropesticides et présentent des symptômes liés à une protection inadéquate. De plus, ils présentent une diminution de la testostérone avec une élévation de l’androstènedione sériques comparé au groupe témoin non exposé (P < 0,05) et ces déséquilibres androgéniques sont accompagnés de difficultés de reproduction. Le manèbe est l’agropesticide le plus utilisé et perturbe chez le rat mâle la stéroïdogenèse Leydigienne (à travers l’inhibition de la CYP11A1) et la fertilité. Cette fertilité est améliorée/rétablie lorsque le pesticide est concomitamment administré avec l’un des extraits, suggérant ainsi l’effet protecteur desdits extraits qui est imputable à leur activité androgénique également démontré chez les rats. Toutefois, ces extraits et le manèbe n’affectent pas la production de la SHBG in vitro. Ces résultats soulignent l’altération de la fonction de reproduction mâle par les agropesticides et l’effet bénéfique des plantes médicinales / The effect of agropesticides use on male reproductive function was evaluated in male farmers in Djutitsa (West Cameroon). The most frequently used agropesticide by farmers was selected and tested in vivo on the reproductive function of male rats, ex vivo and/or in vitro on Leydig cells steroidogenesis, in order to evaluate its implication in disorders observed in farmers. The ability of 2 Cameroonian medicinal plants (Carpolobia alba and Basella alba) to prevent pesticide-induced toxicity was also investigated in vivo in male rats. Furthermore, both extracts and selected pesticide were tested on the release of a steroid transporter protein (SHBG) by HepG2 cells. The results showed that farmers used 25 agropesticides and presented symptoms related to inadequate protection. Moreover, they had lower serum testosterone and higher androstenedione levels compared to a control group with no history of agropesticide exposure (P < 0.05), and these androgenic imbalances were accompanied by difficulties of reproduction. Maneb was the most common ingredient, and its administration to male rats resulted in decrease/alteration of Leydig cells steroidogenesis (through inhibition of CYP11A1) as well as fertility. The latter fertility was improved/restored when maneb was coadministrated to rats with any of the plant extracts, suggesting their protective effect that may be attributed to their proven androgenic activity. However maneb and the plant extracts did not affect SHBG release by HepG2 cells. These results highlight agropesticides deleterious effect on male reproductive function, which may be prevented by the investigated plant extracts

Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and their presence in water bodies is documented. They discharge into surface water (SW) unmonitored, posing a threat to both aquatic and terrestrial lives. This is a challenge as not all populations have access to treated drinking water (TDW). The EDC contaminated serves as a route of exposure, together with ineffective treatment plants. Given the complexity of the endocrine system, EDCs may mimic or antagonise natural hormones or disrupt their synthesis, metabolism and excretion. The associated health effects include testicular dysgenesis syndrome, metabolic disorders and cancers. Policy and internationally standardised test methods are however sti ll limited. This study therefore aimed to assess the suitability of two assays used for screening estrogenic activity and one for androgenic activity in different water sources. The study consisted of two phases. In phase 1, water sample (tap, surface and treated wastewater) were collected from a catchment area in Pretoria. The samples and a spiked MilliQ laboratory water sample were extracted with solid phase extraction (SPE) and sent to Germany for distribution to participating laboratories. Samples (n=24) from six different countries were received to test for androgenic activity in the MDA-kb2 reporter gene assay. In phase 2, SW and TDW samples were collected from April 2015 until March 2016. The samples were filtered, extracted using SPE and assayed with the YES assay, T47D-KBluc reporter gene assay for estrogenic activity and MDA-kb2 reporter gene assay for androgenic activity. In phase 1, androgenic activity was detected in 4 out of 24 (21%) samples and ranged from 0.23 ± 0.040 ng/L to 0.008 ± 0.001 ng/L DHTEqs. In phase 2, estrogenic activity was detected in 16 out of 24 (67%) SW samples in the T47DKBluc reporter gene assay and ranged from 0.31 ± 0.05 pg/L to 10.51 ± 5.74 pg/L EEqs. It was below the detection limit (dl) in the YES assay. Androgenic activity was detected in 4 out of 24 (17%) SW samples, ranging from 0.0033 ± 0.0050 ng/L to 0.090 ± 0.040 ng/L DHTEqs. Androgenic and estrogenic activity was higher i n pretreatment samples compared to post-treatment in both treatment plants. In phase 1, the MDA-kb2 reporter gene assay was successfully applied to water samples from different sources. Androgenic activity was highest in treated wastewater. In phase 2, treatment plants proved to be effective in removing estrogens detected in the SW samples, as the TDW samples were below the dl. Estrogenic activity is within the ranges reported in other studies. Positive samples were below the 0.7 ng/L proposed trigger value for health risk assessments. Detected androgenic activity was lower in TDW samples compared to the SW samples supplying the two treatment plants indicating that they were both effective in removing the androgenic activity detected. Few studies have reported androgenic activity in tap water. This study strengthens the argument for using a battery of assays when monitoring endocrine activity as EDCs occur at low concentrations in mixtures. / Dissertation (MSc)--University of Pretoria, 2017. / School of Health Systems and Public Health (SHSPH) / MSc / Unrestricted