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Background: Indoor residual spraying (IRS) is one of the key interventions recommended by World Health Organization in preventing malaria infection. We aimed to conduct a systematic review and meta-analysis of global studies about the impact of IRS on malaria control., Method: We searched PubMed, Web of Science, Embase, and Scopus for relevant studies published from database establishment to 31 December 2021. Random-effects models were used to perform meta-analysis and subgroup analysis to pool the odds ratio (OR) and 95% confidence interval (CI). Meta-regression was used to investigate potential factors of heterogeneity across studies., Results: Thirty-eight articles including 81 reports and 1,174,970 individuals were included in the meta-analysis. IRS was associated with lower rates of malaria infection (OR = 0.35, 95% CI: 0.27-0.44). The significantly higher effectiveness was observed in IRS coverage ≥ 80% than in IRS coverage < 80%. Pyrethroids was identified to show the greatest performance in malaria control. In addition, higher effectiveness was associated with a lower gross domestic product as well as a higher coverage of IRS and bed net utilization., Conclusions: IRS could induce a positive effect on malaria infection globally. The high IRS coverage and the use of pyrethroids are key measures to reduce malaria infection. More efforts should focus on increasing IRS coverage, developing more effective new insecticides against malaria, and using multiple interventions comprehensively to achieve malaria control goals., (© 2022. The Author(s).)

Exposure to fenvalerate has been shown to be associated with decreased steroid hormone production by mouse Leydig tumor cells (MLTC-1) in our previous study and the interference with cAMP-PKA pathway cannot explain this inhibitory effect completely. In this study, the same cell line was used to investigate the potential involvement of insulin-like growth factor I (IGF-I) signaling pathway in the downregulation of steroidogenesis by fenvalerate. Results showed that fenvalerate treatment decreased IGF-I secretion significantly which was consistent with the reduced expression of IGF-I mRNA. Then inhibitors of the two downstream pathways of IGF-I were added to the medium. The addition of LY294002 (inhibitor of phosphatidylinositol (PI)-3-kinase) did not alter the declining trend of progesterone production with increasing dosages of fenvalerate treatment while the addition of UO126 (inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2)) markedly attenuated this trend, which strongly indicated the possible involvement of pathway ERK1/2. In addition, phosphorylation of ERK1/2 was also suppressed by fenvalerate. The results suggest that the mechanism by which fenvalerate decreased steroid hormone production might involve the impairment of IGF-I signal pathway by attenuating the IGF-I production and ERK1/2 phosphorylation., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Fenvalerate is a widely used synthetic pyrethroid insecticide and is reported to disrupt reproductive function in humans and animals. However, little is known about its influence on follicular development. In this study, rat preantral follicles were primary cultured to investigate the effects of fenvalerate on follicular survival rate, morphological change, steroid hormone levels and steroidogenesis related gene mRNA expression. Follicles were cultured with 0, 1, 5 and 25 micromol/L fenvalerate for 72 h. And then the morphous was assessed by conventional light microscopy, steroid hormones were measured by RIA, and the expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage enzyme (P450scc) were monitored by real-time quantitative PCR analysis. Results showed that fenvalerate inhibited the augmentation of follicular diameters but did not have detectable effects on follicular survival rates. The level of steroid hormones, such as progesterone, testosterone and estradiol, was inhibited. The inhibition might be due to the decreased expression levels of StAR and P450scc. These results suggested that fenvalerate restrained the follicular growth, and inhibited steroidogenesis by reducing StAR and P450scc gene expression, which might further contribute to the fenvalerate-induced reproductive dysfunction., (2009 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the joint toxicity of phoxim (Pho) and fenvalerate (Fen) on the spermatogenesis of male rats and to clarify its mechanism., Methods: Based on the three administrative levels of factorial analysis (3 x 3) of Pho and Fen, i. e. their half lethal dose (LD50) 1/250 LD50 (5.9, 2.4 mg/kg) and 1/50 LD50 (29.4, 12.0 mg/kg) and the control, 135 adult male SD rats were randomly assigned to9 groups, the control (0.0 mg/kg), Pho (5.9, 29.4 mg/kg), Fen (2.4, 12.0 mg/kg), Pho + Fen (5.9 + 2.4, 5.9 + 12.0, 29.4 + 2.4, 29.4 + 12.0 mg/kg), and treated intragastrically with different doses of Pho, Fen and Pho + Fen for 15 and 30 days. The levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and testis homogenate T were determined by radioimmunoassay (RIA), the activity of testicular marker enzymes such as acid phosphatases (ACP) and gamma-glutamyl transpeptidase (gamma-GT) examined, and the sperm head count measured for the changes of daily sperm production (Spr)., Results: At 15 days, obvious interaction was observed between Pho and Fen in both serum LH and FSH (P < 0.05), as well as between their reproductive toxicities. With the increase in doses, the joint action was synergistic in LH (P < 0.05) and antagonistic in FSH (P < 0.01) at a high dose ( 29.4 + 12.0 mg/kg). At 30 days, marked interaction between Pho and Fen was noted in the content of homogenate T (P < 0.05) , with a joint synergistic effect. At 15 and 30 days, with the increase of doses, both Pho and Fen reduced Spr and the activity of ACP and gamma-GT, but Pho + Fen showed no obvious interaction in them (P > 0.05) , and their joint action was an additive effect., Conclusion: Pho and Fen jointly impaired spermatogenesis in a dose- and time-dependent manner. Their joint action exhibited mainly as a synergistic effect, an additive effect and increased toxicity.

Fenvalerate is a widely used synthetic pyrethroid insecticide and is known to impede the male reproductive function. However, the mechanisms remain to be elucidated. In this study, mouse Leydig tumor cells (MLTC-1) were used to investigate the effects of fenvalerate on progesterone production. Fenvalerate treatment inhibited progesterone secretion induced by human chorionic gonadotropin (hCG), cholera toxin (CT) or forskolin and decreased cAMP levels induced by hCG, but not by CT or forskolin, which suggested a repaired site on the upstream components of G protein or G protein per se by fenvalerate in the cAMP-mediated signal pathway. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse fenvalerate-suppressed progesterone synthesis, indicating that fenvalerate interfered with the downstream molecules of cAMP. In addition, fenvalerate decreased steroidogenic acute regulatory protein (StAR) mRNA and protein levels, and also profoundly inhibited the activity of P450 side chain cleavage enzyme (P450scc) which was consistent with the decreased expression of P450scc mRNA and protein in MLTC-1 cells. These results suggested that fenvalerate might inhibit progesterone production by attenuating cAMP generation and inhibiting StAR expression and P450scc activity.

Fenvalerate and cypermethrin were reported to impair male reproductive function, inducing significant reductions in epididymal sperm count. Further, fenvalerate was shown to reduce sperm motility. However, it is not clear whether fenvalerate and cypermethrin might impact sperm motility directly or indirectly by affecting spermatogenesis via interaction with androgens or their receptors. In this study, sperm suspensions were treated with fenvalerate and cypermethrin, respectively, at various concentrations (0, 1, 4, 16, or 64 micromol/L) for various times (1, 2, or 4 h). The motility parameters of sperm treated with these two insecticides were analyzed with a computer-assisted sperm analysis (CASA) system. The differential effects of fenvalerate and cypermethrin on rat sperm motility patterns in vitro were also compared. Our study revealed that fenvalerate and cypermethrin reduced sperm motility in vitro in a concentration- and time-dependent manner. Cypermethrin exerted a greater effect on sperm motility in comparison to fenvalerate. These results provided evidence that fenvalerate and cypermethrin directly influence mature rat sperm motility.

Objective: To observe the direct effects of fenvalerate (Fen) on sperm motility in SD rats., Methods: Sperm were isolated from caudal epididymides of healthy adult male rats with the diffusion method. The motility parameters of the isolated sperm, such as VCL, VSL, VAP, BCF, STR and LIN, were monitored by computer-assisted sperm analysis (CASA) system after 1, 2 and 4 h Fen-exposure in vitro at concentrations of 0, 1, 4, 16 and 64 micromol/L respectively., Results: After 1 and 2 h Fen-exposure, VSL, BCF, STR and LIN decreased significantly at 64 micromol/L compared with the control group. After 4 h Fen-exposure, the motility parameters VCL, VSL, BCF, STR and LIN dropped progressively at 64 micromol/L, and VCL declined markedly at 16 micromol/L. However, only VCL and STR showed alterations in a time-response manner., Conclusion: Fen may affect the caudal epididymal sperm and produce a direct toxic effect on sperm motility in SD rats.

Many pesticides possess hormonal activity and have thus been classified as endocrine disruptors. Pyrethroids are commonly used pesticides worldwide, but little has been done to characterize their antiandrogenic activity potential. We tested three frequently encountered pyrethroids (fenvalerate, cypermethrin, permethrin) and their metabolite 3-phenoxybenzoic acid (3-PBA) for antiandrogenic and androgenic activity using a human androgen receptor (AR) mediated luciferase reporter gene assay in CV-1 African green monkey kidney cell. The assay displayed appropriate response to the known AR agonist 5alpha-dihydrotestosterone and AR antagonist nilutamide and flutamide. At 0.1mM, all the three tested pyrethroids significantly suppressed the luciferase expression. Further, their metabolite 3-PBA also showed antagonist activity. None of the test chemicals showed androgenic activity. Through the antiandrogenic pathways, exposure to certain pyrethroids may contribute to the damage of reproductive system. In conclusion, pyrethroid pesticides can act as antiandrogen in vitro, and metabolizing to 3-PBA cannot eliminate the antagonist activity. This result provides useful information for risk assessment of pyrethroid pesticides.

Objective: To observe the effects of fenvalerate on calcium homeostasis in rat ovary., Methods: Female Sprague-Dawley rats were orally given fenvalerate at daily doses of 0.00, 1.91, 9.55, and 31.80 mg/kg for four weeks. The ovary ultrastucture was observed by electron microscopy. Serum free calcium concentration was measured by atomic absorption spectrophotometry. The activities of phosphorylase a in rat ovary were evaluated by the chromatometry. The total content of calmodulin in ovary was estimated by ELISA at each stage of estrous cycle. Radioimmunoassay (RIA) was used to evaluate the level of serum progesterone., Results: Histopathologically, damages of ovarian corpus luteum cells were observed. An increase in serum free calcium concentration was observed in rats treated with 31.80 mg/kg fenvalerate. The activities of phosphorylase a enhanced in all treated groups, and fenvalerate increased the total content of calmodulin significantly in estrus period. Serum progesterone levels declined in fenvalerate exposed rats in diestrus., Conclusion: Fenvalerate interferes with calcium homeostasis in rat ovary. Also, the inhibitory effects of fenvalerate on serum progesterone levels may be mediated partly through calcium signals.

In this study, we have developed a transient human androgen receptor (hAR) reporter gene assay using African monkey kidney cell line CV-1. The assay displayed appropriate response to the known androgen receptor (AR) agonist 5alpha-dihydrotestosterone (DHT) and AR antagonist nilutamide. DHT induced AR-mediated transcriptional activity in a concentration-dependent manner with median effective concentration (EC(50)) value of 3.90 x 10(-10) M. Nilutamide exhibited potent antiandrogenic activity with median inhibitory concentration (IC(50)) value of 8.90 x 10(-7) M. The transcription could not be activated by glucocorticoid receptor (GR) agonist dexamethasone, which suggested that the assay system be highly specific to androgenic compounds without cross-talk to GR agonist. The assay shows acceptable repeatability to DHT with intra coefficient of variability (CV) of 9.3% and inter CV of 10.9%. We applied this assay to evaluate the androgenic and antiandrogenic activities of some pesticides including organochlorine p,p'-dichlorodiphenyldichloroethylene (DDE), pyrethroid fenvalerate and organophosphorus phoxim. The results showed that p,p'-DDE exhibited potent antiandrogenic activity. Fenvalerate acted as weak AR antagonist and phoxim did not show AR antagonistic activity. We failed to find AR agonistic effects of the three pesticides. The present study provided a promising tool to screen for AR agonists and antagonists.

Objective: This study was designed to examine the in vitro effects of fenvalerate on steroid production and steroidogenic enzymes mRNA expression level in rat granulosa cells., Methods: Using primary cultured rat granulosa cells (rGCs) as model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 micromol/L) was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)-hydroxycholesterol (25 micromol/L), Follicle stimulating hormone (FSH, 2 mg/L), or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17 beta-estradiol(E2) and progesterone (P4) in the medium from the same culture wells were measured by RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative RT-PCR., Results: Fenvalerate decreased both P4 and E2 production in a dose-dependent manner while it could significantly stimulate rGCs proliferation. This inhibition was stronger in the presence of FSH. Furthermore, it could not be reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that fenvalerate had no significant effect on 3 beta-HSD, but could increase the P450scc mRNA level. In addition, 17 beta-HSD mRNA level was dramatically reduced with the increase of fenvalerate dose after 24 h treatment., Conclusion: Fenvalerate inhibits both P4 and E2 production in rGCs. These results support the view that fenvalerate is considered as a kind of endocrine-disrupting chemicals. The mechanism of its disruption may involve the effects on steroidogenesis signaling cascades and/or steroidogenic enzyme's activity.

Aim: To evaluate the joint action of phoxim and fenvalerate on the reproductive function in male Sprague-Dawley rats., Methods: The 2 x 2 factorial analysis experiment was used in the study. The pesticides were orally given at daily doses of phoxim (Pho) 8.2 mg/kg, fenvalerate (Fen) 3.3 mg/kg and Pho 8.2+Fen 3.3 mg/kg (Pho:Fen = 5:2), 5 days a week for 60 days. Sperm motility was measured with computer-assisted sperm motility analysis (CASA) and daily sperm production estimated. Immunoenzymatic method and electron microscopy were used to evaluate the serum testosterone and the testicular morphology, respectively., Results: There were significant decreases in sperm motility parameters in the treated animals, including straight line velocity (VSL), beat cross frequency (BCF), linearity (LIN) and straightness (STR). After treated with Fen, significant decreases in VSL, LIN and STR were demonstrated. Significant decreases of daily sperm production were seen in animals treated with Pho and Pho+Fen in comparison with the controls. Serum testosterone levels were not significantly changed in the treated groups. Factorial ANOVA showed that no significant interactions were noted between Pho and Fen in sperm motility, sperm production and serum testosterone. Both the single and mixed pesticides caused various degrees of testicular lesions, involving vacuolation of endoplasmic reticulum and necrosis of Sertoli cells., Conclusion: The pesticides may cause sperm motility changes and testicular lesions in male rats. The action of Pho and Fen may be additive.

Aims: To determine sperm nuclear DNA integrity and to investigate the relation between fenvalerate (FE) exposure and spermatozoa DNA damage., Methods: Sperm DNA fragmentation was detected by a modified alkaline single cell gel electrophoresis (Comet) assay and a terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) assay. The olive tail moment (OTM) and percentage tail DNA were measured by the Comet assay, and cell positive percentage was measured by the TUNEL assay for DNA damage evaluation., Results: The DNA integrity of spermatozoa of external and internal control groups were both significantly greater than that of the FE exposed group. The median value of tail DNA percentage in the exposure group was 11.30, which was significantly higher than 5.60 in the internal control group and 5.10 in the external control group. The median value of OTM was 3.80 in the exposure group, significantly higher than 1.50 in the internal control group and 2.00 in the external control group. Mean cell positive was 31.2% in the exposure group, significantly higher than 17.4% in the internal control and 19.6% in the external control groups. Cell positive (%) was significantly correlated with tail DNA percentage and with OTM of whole subjects (n = 63)., Conclusions: Results showed that occupational FE exposure is associated with an increase in sperm DNA damage. A combination of the Comet and TUNEL assays would offer more comprehensive information for a better understanding of sperm DNA damage, and the biological significance of sperm DNA damage in sperm function and male infertility.

Objective: To observe the effects of fenvalerate (Fen) on ovarian calcium homeostasis., Methods: hGLCs were obtained from pre-ovulatory follicles in an in vitro fertilization program, and were cultured for 72 hours. Changes in cellular [Ca(2+)]i induced by Fen in hGLCs were detected with laser scanning confocal microscopy (LSCM) by using the fluorescent Ca(2+) indicator fluo-3/AM. SD female rats were divided into four groups (control, 1/15LD(50), 1/50 LD(50) and 1/250 LD(50)) in experiment. The activity of ovarian Ca(2+)-ATPase and phosphorylase A (P-a) and the contents of calmodulin (CaM) were assessed after a 30-day Fen exposure. In addition, serum estradiol-17 beta (E(2)) and progesterone (P(0)) concentration were measured by radioimmunoassay, which the sampling rats were ensured at diestrus stage before killed according to vaginal smear., Results: 20.0 and 2.0 micromol/L Fen induced the increased of [Ca(2+)]i in hGLC. This [Ca(2+)]i increase mostly resulted from Ca(2+) influx in the studied concentration. Fen had shown the inhibition effects on activity of Ca(2+)-ATPase in 1/250 LD(50) group (P < 0.001) while the activity of phosphorylase A (P-a) in treated groups had significantly enhanced than those of in control. The contents of CaM in ovaries were found to be increased in treated groups. E(2) in 1/250 LD(50) group were higher while P(0) in 1/15 LD(50) group were significantly lower (P < 0.05)., Conclusion: Exposure to Fen interferes the serum steroid hormone concentrations partly through calcium signal pathway.

Objectives: To evaluate the impairment of fenvalerate on reproductive and endocrine systems and clarify the mechanism of action., Methods: Different doses of fenvalerate (0, 2, 4, 12, 60 mg/kg) were orally treated to the adult male SD rats for 15 days and 30 days, respectively. The levels of serum follicle stimulating hormone(FSH), luteinizing hormone (LH), testosterone(T) and testis homogenate T were determined by radioimmunoassay(RIA). Besides, the activity of testicular marked enzymes such as acid phosphatases(ACP) and gamma-glutamyl transpeptidase(gamma-GT) were examined, and sperm head counts were measured to explain the changes of daily sperm production(Spr)., Results: In fifteen days, serum FSH levels markedly increased in rats exposed to fenvalerate of < or = 12 mg/kg groups(P < 0.01) and serum levels of LH increased in 12 mg/kg group(P < 0.01). In addition, T levels in testis homogenates decreased after treated with the doses of > or = 12 mg/kg groups compared with the control group(P < 0.01). In thirty days, serum contents of FSH were significantly elevated in the doses of > or = 12 mg/kg groups(P < 0.01) and homogenate levels of T were diminished in the low dose group(2.4 mg/kg) (P < 0.05). Activity of ACP increased in 12 mg/kg group after fifteen days(P < 0.05) and was restrained in the high dose group(60 mg/kg) in thirty days(P < 0.05), but the contents of gamma-GT were arrested with different doses dependently in the testis(P < 0.05). Fenvalerate caused dose-dependent reduction in sperm head counts and daily sperm production, which markedly reduced at the doses of > or = 12 mg/kg groups(P < 0.01)., Conclusions: Fenvalerate has obvious reproductive toxicity on male rats and can change their serum and testis homogenate levels of sex hormone or activity of testicular marked enzymes, which may be correlated with the impairment of Sertoli cell and spermatogenic epithelium.

Objectives: To study the effects of fenvalerate exposure on the semen quality of occupational workers in order to find out the early effective biomarkers., Methods: Thirty-two male workers who exposed to fenvalerate and 46 male administrators in the office in a pesticide factory were selected as the exposure group and internal control group, respectively, and 22 male administrators in a center for disease control were served as the external control group. In order to evaluate the exposed levels, the concentration of fenvalerate, toluene and xylene in the ambient air of working place in these three groups were monitored simultaneously for three consecutive days. After the semen were collected according to the standard method, the workers' semen qualities were analysed with University of California at Davis (UCDavis) method and the sperm motility were evaluated using computer assisted sperm analysis(CASA)., Results: In the exposure group, the concentrations of fenvalerate were significantly higher than those in the internal and external control group (P < 0.01), while no significant difference of the concentration on toluene or xylene was found (P > 0.05). Sperm motion parameters in the exposure group such as linearity(LIN), straightness(STR), and the sperm count were decreased significantly, and the abnormality rate of viscidity, coagulation and sperm count were increased significantly as compared with the internal and the external control groups(P < 0.05). Furthermore, the sperm progression and beat cross frequency (BCF) in the exposure group were also lower significantly than those in the external control group(P < 0.05), while the abnormality rate of sperm progression was increased significantly., Conclusions: In such a low concentration, occupational exposure to fenvalerate can affect workers' semen quality, especially the sperm count and sperm movement ability.

On 1 d after instillation of fenvalerate (Fen) 0.19, 0.93, 4.66, and 23.3 mg.kg-1, and on 30 min, 4 h, 1 d, 4 d, and 7 d after instillation of Fen 4.66 mg.kg-1 by a single intratracheal instillation, respectively, the ultrastructural changes in rat pulmonary alveolar macrophages (PAM) were observed, and the toxicity indices (TI) were calculated. It was found that the ineffective dose of Fen was 0.19 mg.kg-1, and the threshold dose was less than or equal to 0.93 mg.kg-1 as well as the serious intoxication dose greater than or equal to 4.66 mg.kg-1. The results suggest that Fen is quickly toxic to rat lungs and quickly biodegraded in the lungs.