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1.
J Infect Dis ; 230(1): e149-e158, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39052707

RESUMEN

BACKGROUND: Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. METHODS: In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd-I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd, bo', or aa3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. RESULTS: The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd-I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli "bd-I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus "bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. CONCLUSIONS: Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus.


Asunto(s)
Antibacterianos , Escherichia coli , Staphylococcus aureus Resistente a Meticilina , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/enzimología , Antibacterianos/farmacología , Simulación del Acoplamiento Molecular , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/metabolismo , Pruebas de Sensibilidad Microbiana , Esteroides/farmacología , Esteroides/química , Proteínas del Complejo de Cadena de Transporte de Electrón/antagonistas & inhibidores , Proteínas del Complejo de Cadena de Transporte de Electrón/metabolismo , Grupo Citocromo b , Citocromos/antagonistas & inhibidores , Citocromos/metabolismo
2.
Integr Zool ; 19(1): 127-142, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37884475

RESUMEN

Pest rodents pose a serious threat to island biodiversity. Fertility control could be an alternative approach to control the impact of rodents on these islands. In this study, we examined the antifertility effects of EP-1 baits containing quinestrol (E) and levonorgestrel (P) using a dose of 50 ppm E and P at three different ratios (E:P ratio = 1:2, 1:1, and 2:1) on Pacific rats (Rattus exulans) in the Xisha Islands, Hainan, China. Compared to the control group, all animals in EP-1 treatment groups showed significantly decreased food intake and body weight. In treated males, there were obvious abnormalities in testis structure and a significant decrease of relative seminal vesicle weight, but no significant effect on relative uterine and ovarian weights (g kg-1 body weight), or ovarian structure in females. Adding 8% sucrose to the original 50-ppm baits (E:P ratio = 1:1) significantly increased bait palatability for males and females. This dose induced uterine edema and abnormalities of ovarian structure in females but had no significant negative effect on the relative testis, epididymis, and seminal vesicle weights (g kg-1 body weight) or sperm density in males. In summary, 50-ppm EP-1 (1:1) baits have the potential to disrupt the fertility of females, and 8% sucrose addition to the EP-1 baits (E:P ratio = 1:1) could improve bait palatability. This dose disrupted the testis structure in males. Future studies are needed to improve bait acceptance and assess the antifertility effects of EP-1 (1:1) on Pacific rats in captive breeding trials and under field conditions.


Asunto(s)
Levonorgestrel , Quinestrol , Femenino , Ratas , Masculino , Animales , Levonorgestrel/farmacología , Quinestrol/farmacología , Semen , Peso Corporal , Sacarosa
3.
Integr Zool ; 19(1): 108-126, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37231968

RESUMEN

Integrating fertility control techniques using steroid hormones after lethal control can help reduce post control rebuildup of rodent populations. The current study is the first to assess the antifertility effects of quinestrol in male lesser bandicoot rat, Bandicota bengalensis which is the predominant rodent pest species in Southeast Asia. Rats in different groups were fed bait containing 0.00%, 0.01%, 0.02%, and 0.03% quinestrol for 10 days in laboratory and evaluated immediately, and 15, 30, and 60 days after treatment discontinuation for effect on reproduction and other antifertility parameters. Effect of 0.03% quinestrol treatment for 15 days was also observed in managing rodent populations in groundnut crop fields. Treatment resulted in average consumption of 19.53 ± 1.80, 67.63 ± 5.50, and 246.67 ± 1.78 mg/kg bwt active ingredient by three treated groups of rats, respectively. No reproduction was observed in female rats mated with male rats treated with 0.03% quinestrol, even 30 days after cessation of treatment. Post-mortem examination showed a significant (P < 0.0001) effect of treatment on organ weights (testis, cauda epididymis, seminal vesicles, and prostate gland) and different sperm parameters (sperm motility, sperm viability, sperm count, and sperm abnormality) in the cauda epididymal fluid with partial reversibility after 60 days. A significant (P < 0.0001) effect of quinestrol on the histomorphology of testis and cauda epididymis was observed, suggesting its effect on spermatogenesis. Affected cell association and cell count in seminiferous tubules did not fully recover within 60 days of stopping treatment. Evaluation of the effects of quinestrol treatment in groundnut fields showed greater reductions in rodent activity in fields treated with 2% zinc phosphide followed by 0.03% quinestrol treatment as compared to fields treated with 2% zinc phosphide alone. Research concludes that quinestrol has the potential to reduce fecundity and post control rebuildup of B. bengalensis populations, but long-term studies of the effectiveness of quinestrol under large-scale field conditions are needed to use it as part of an integrated pest control program for rodents.


Asunto(s)
Murinae , Quinestrol , Masculino , Ratas , Femenino , Animales , Quinestrol/farmacología , Motilidad Espermática , Semen , Testículo/anatomía & histología , Epidídimo/anatomía & histología , Espermatozoides , Tamaño de los Órganos
4.
Integr Zool ; 17(6): 1002-1016, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35271766

RESUMEN

The plateau zokor (Eospalax baileyi) is a key species in the Qinghai-Tibetan Plateau ecosystem, and fertility control could be an ideal approach to manage populations of this subterranean species. In this laboratory study, we explored the effects of the mixture of levonorgestrel and quinestrol (EP-1, 1:2), quinestrol (E), and levonorgestrel (P) on the reproductive status of plateau zokors. Groups of 5 animals of each sex were treated with different concentrations of EP-1 (1, 5, and 10 mg/kg), E (0.33, 3.3, and 6.6 mg/kg), and P (0.67, 3.35, and 6.7 mg/kg) by oral gavage over 7 successive days and killed on day 15. Body mass reduction was observed in the EP-1 and E groups. EP-1 and E significantly reduced the weight of testis and epididymis at 10 and 3.3 mg/kg, respectively. Sperm count and motility were significantly reduced by 5 mg/kg EP-1 and 0.33 mg/kg E. The levels of serum testosterone, estradiol, luteinizing hormone, and follicle stimulating hormone were significantly reduced by 5 mg/kg EP-1 and 3.3 mg/kg E. EP-1 and E significantly increased the uterine and ovarian weights at 10 and 3.3 mg/kg, respectively. In the plateau zokors, treatment with P had no influence on the reproductive status. These data demonstrate that EP-1 and E have an inhibitory effect on a range of reproductive parameters in the plateau zokors. Further assessment is required to determine the effects on breeding and recruitment in enclosure or field experiments.


Asunto(s)
Levonorgestrel , Quinestrol , Masculino , Animales , Quinestrol/farmacología , Levonorgestrel/farmacología , Ecosistema , Tibet , Semen , Muridae
5.
Integr Zool ; 17(6): 964-980, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34549512

RESUMEN

Management of overabundant rodents at a landscape scale is complex but often required to sustainably reduce rodent abundance below damage thresholds. Current conventional techniques such as poisoning are not species specific, with some approaches becoming increasingly unacceptable to the general public. Fertility control, first proposed for vertebrate pest management over 5 decades ago, has gained public acceptance because it is perceived as a potentially more species-specific and humane approach compared with many lethal methods. An ideal fertility control agent needs to induce infertility across one or more breeding seasons, be easily delivered to an appropriate proportion of the population, be species specific with minimal side-effects (behavioral or social structure changes), and be environmentally benign and cost effective. To date, effective fertility control of rodents has not been demonstrated at landscape scales and very few products have achieved registration. Reproductive targets for fertility control include disrupting the hormonal feedback associated with the hypothalamic-pituitary-gonadal axis, gonad function, fertilization, and/or early implantation. We review progress on the oral delivery of various agents for which laboratory studies have demonstrated efficacy in females and/or males and synthesize progress with the development and/or use of synthetic steroids, plant extracts, ovarian specific peptides, and immunocontraceptive vaccines. There are promising results for field application of synthetic steroids (levonorgestrel, quinestrol), chemosterilants (4-vinylcyclohexene diepoxide), and some plant extracts (triptolide). For most fertility control agents, more research is essential to enable their efficient and cost-effective delivery such that rodent impacts at a population level are mitigated and food security is improved.


Asunto(s)
Quinestrol , Roedores , Masculino , Femenino , Animales , Quinestrol/farmacología , Fertilidad , Reproducción , Anticoncepción
6.
Integr Zool ; 17(6): 1028-1040, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34496452

RESUMEN

The multimammate mouse, Mastomys natalensis, is the most common rodent pest species in sub-Saharan Africa. Currently, rodenticides are the preferred method used to reduce the population of rodent pests, but this method poses direct and indirect risks to humans and other non-target species. Fertility control is a promising alternative that has been argued to be a more sustainable and humane method for controlling rodent pests. In this study, we compared the effectiveness of fertility control bait EP-1 (quinestrol (E) and levonorgestrel (P), 10 ppm) and an anticoagulant rodenticide bait (bromadiolone, 50 ppm) on the population dynamics of M. natalensis in maize fields in Zambia during 2 cropping seasons. M. natalensis was the most abundant species in maize fields (77% of total captures). Fertility control reduced the number of juveniles and suppressed population growth of M. natalensis at the end of the 2019-2020 cropping season. The population density initially decreased after rodenticide treatment, but the population rapidly recovered through immigration. None of the treatments influenced maize damage by rodents at germination (F2,67 = 1.626, P = 0.204). Applying the treatments during the maize seeding time was effective at suppressing population growth at the end of the cropping season than application the month before maize seeding. This research indicates that a single-dose delivery of EP-1 and rodenticide have comparable effects on the population dynamics of M. natalensis. These findings are important in developing fertility control protocols for rodent pest populations to reduce maize crop damage and improve yields.


Asunto(s)
Rodenticidas , Zea mays , Humanos , Ratones , Animales , Rodenticidas/farmacología , Murinae , Fertilidad , Dinámica Poblacional
7.
Integr Zool ; 17(6): 1053-1062, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34605180

RESUMEN

Fertility control agents for the management of rodent populations are developing and maturing. Investigating the impacts on non-target species of consumption of these agents is essential. The present study assessed the non-target toxicity effects of quinestrol, a synthetic estrogen-based antifertility agent for managing rodent populations. Various quinestrol doses administered to male and female (n = 60 each) chickens through single oral gavage were 0 (A), 10 (B), 50 (C), and 150 (D) mg/kg body weight. Chickens were assessed for effect on body weight, weight of vital and reproductive organs, reproductive hormones, histology of reproductive organs and egg laying rates after 15, 30, and 135 days of treatment. Quinestrol did not induce mortality in chickens and its effects were time and dose dependent. The 90% egg-laying rates were delayed by 30, 60 for groups B and C compared with the control group, and group D did not reach the 90% egg-laying rate by 135 days. Reproductive organs in males and females returned to normal levels within 30 and 135 days, respectively. With the exception of the FSH concentration in group D, reproductive hormones of both sexes were similar to controls by 30 days. No other significant effects were found. The present research demonstrated the safety of quinestrol on non-target species and facilitates recommendations for the general administration of quinestrol for rodent pest management.


Asunto(s)
Estradiol , Quinestrol , Femenino , Animales , Masculino , Quinestrol/farmacología , Pollos , Peso Corporal
8.
Integr Zool ; 17(6): 991-1001, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34047451

RESUMEN

The black rat is considered one of the world's top pests. With increased restrictions on rodenticides, new alternatives to manage rats are urgently needed. Research on the use of contraceptive hormones, levonorgestrel (LE), and quinestrol (QU), have been evaluated against some rodent species, and this research is the first study to assess these on black rats. Hormones were incorporated into rodent bait at 10 and 50 ppm concentrations singly and in combination (EP-1). Groups of 10 animals of each sex were fed the baits over 7 days. Lower bait consumption was observed with slight body mass reductions. On dissection, it was observed that the uterus was in a state of edema and male reproductive organs weighed less with reduced sperm counts/motility. The 2 most promising baits, 50 ppm QU and EP-1, were used to assess impact on pregnancy and litter size. Pregnancy was reduced from 70% success when both males and females consumed untreated bait, down to 30% when males had consumed contraceptive bait but females had not, and down to 0% when females had consumed contraceptive bait, regardless of whether they had paired with a treated or untreated male. Litter size in the untreated pairs was 8 pups, but only 4 pups in those cases where the male only had consumed the contraceptive. Further studies should investigate how long the effect lasts and its reversibility. Field studies at the population level may also shed light on the practicality of using contraceptive baits for black rats in different habitats.


Asunto(s)
Anticonceptivos , Semen , Embarazo , Masculino , Ratas , Femenino , Animales , Anticonceptivos/farmacología , Reproducción , Quinestrol/farmacología
9.
Integr Zool ; 17(6): 1041-1052, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34216194

RESUMEN

The effect of combined levonorgestrel (P) and quinestrol (E) on the fertility of striped field mouse (Apodemus agrarius) has not been evaluated. We performed a series of experiments in both the laboratory and field to assess the effect of P and/or E on the fertility of A. agrarius. In the laboratory, to test the time-dependent anti-fertility effects of P and E, as well as their mixtures, 90 male striped field mice were randomly assigned to 6 treatment groups (n = 60), and a control group (n = 30). Mice in 3 treatment groups were administered 1 of the 3 compounds (1 mg⋅kg- 1 [body weight] EP-1, 0.34 mg⋅kg-1 E, 0.66 mg⋅kg-1 P) for 3 successive days (another half for 7 successive days) via oral gavage; mice were then sacrificed 15 and 45 days after initiating the gavage treatment. Our findings indicated that E and EP-1 treatment, but not P or control treatment, significantly decreased the sperm count in the caudal epididymis, as well as the weight of the testes, epididymides, and seminal vesicles. Additionally, fertile female mice mated with E- and EP-1-treated males produced smaller pups. These data indicate that E and EP-1 can induce infertility in male A. agrarius. In the field, the population density of A. agrarius was significantly influenced by EP-1, and the rodent density in the treatment group was lower than that in the control group. Overall, our results indicate that EP-1 is an effective contraceptive in A. agrarius, a dominant rodent species in the farmland.


Asunto(s)
Fármacos para la Fertilidad , Quinestrol , Masculino , Femenino , Ratones , Animales , Quinestrol/farmacología , Levonorgestrel/farmacología , Semen , Murinae
10.
PeerJ ; 8: e9140, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32566388

RESUMEN

BACKGROUND: Rodent pests can inflict devastating impacts on agriculture and the environment, leading to significant economic damage associated with their high species diversity, reproductive rates and adaptability. Fertility control methods could indirectly control rodent pest populations as well as limit ecological consequences and environmental concerns caused by lethal chemical poisons. Brandt's voles, which are common rodent pests found in the grasslands of middle-eastern Inner Mongolia, eastern regions of Mongolia, and some regions of southern Russia, were assessed in the present study. METHODS: We evaluated the effects of a 2-mg/kg dose of levonorgestrel and quinestrol and a 1:1 mixture of the two (EP-1) on reproductive behavior as well as changes in the reproductive system, reproductive hormone levels, and toxicity in Brandt's voles. RESULTS: Our results revealed that all three fertility control agents can cause reproductive inhibition at a dosage of 2 mg/kg. However, quinestrol caused a greater degree of toxicity, as determined by visible liver damage and reduced expression of the detoxifying molecule CYP1A2. Of the remaining two fertility control agents, EP-1 was superior to levonorgestrel in inhibiting the secretion of follicle-stimulating hormone and causing reproductive inhibition. We believe that these findings could help promote the use of these fertility control agents and, in turn, reduce the use of chemical poisons and limit their detrimental ecological and environmental impacts.

11.
Pestic Biochem Physiol ; 165: 104544, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32359538

RESUMEN

The present study was aimed to evaluate the toxic effects of quinestrol (a synthetic estradiol) in male lesser bandicoot rat, Bandicota bengalensis. Effect was studied on body weight, weight of vital organs, changes in level of biochemical parameters and genotoxicity. Feeding of bait containing 0.01% quinestrol in bi-choice and 0.02 and 0.03% quinestrol in no-choice for a period of 10 days resulted in total ingestion of 19.50, 67.60 and 243.30 mg/kg bwt, respectively of the active ingredient. Autopsy of rats after 15 and 30 days of treatment withdrawal revealed no significant effect on body weight and weights of vital organs of rats. A significant decrease in the testicular levels of 17-beta hydroxysteroid dehydrogenase and increase in total soluble proteins was observed in rats treated with 0.02 and 0.03% quinestrol. The plasma levels of lipid peroxidation in the form of malondialdehyde concentration and lactate dehydrogenase increased significantly whereas the level of testosterone decreased significantly in treated rats. The plasma levels of acid and alkaline phosphatases, superoxide dismutase and total proteins differed non-significantly among rats of treated and untreated groups. The effect was found reversed partially in rats autopsied after 60 days of treatment withdrawal. No micronuclei in bone marrow cells, no aberrations in chromosomes and no DNA damage in blood cells during comet assay indicated no genotoxic effect of quinestrol on B. bengalensis at the test doses administered. The results thus revealed that quinestrol causes reversible toxic effects in the form of oxidative stress, increased lytic enzyme activity and decreased steroidogenesis which may further lead to testicular damage thereby inhibiting reproductive function. Also more effect was shown at higher doses ingested in no-choice test as compared to low doses ingested in bi-choice tests.


Asunto(s)
Murinae , Quinestrol , Animales , Peso Corporal , Estrógenos , Masculino , Ratas , Testículo
12.
Physiol Behav ; 219: 112848, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32088172

RESUMEN

Quinestrol and levonorgestrel (EP-1, at a ratio of 1:2) are often used as anti-fertility compounds (sterilants) in rodents. As most of the research has focused on the sterility and damage caused in parental reproductive organs, there is little research on the effect of these contraceptive hormones on maternal behavior and offspring's early development. In this study, we examined maternal behavior after treatment with different doses of EP-1 (10 ml/kg) at postnatal days 3 and 10, separately. Various parameters were measured after treatment, including oxytocin expression, serum levels of estradiol and luteinizing hormone (LH), ovary damage after weaning of offspring, as well as the development and ultrasonic vocalizations (USVs) of midday gerbil (Meriones meridianus) offspring. At postnatal days 5 and 12, the EP-1 increased maternal licking, grooming, and retrieving behavior, while reducing contacting behavior. Oxytocin expression in the hypothalamic paraventricular and supraoptic nuclei increased, while the levels of estradiol and LH decreased. The ovaries and the development of follicles were clearly affected by the treatment. The EP-1 significantly reduced the pups' body weight, the amount and pulse duration of USVs, whereas the frequency range variation of USVs was increased. Overall, treatment with EP-1 during lactation significantly affected maternal behavior and impaired offspring early development in the midday gerbil.


Asunto(s)
Levonorgestrel , Quinestrol , Animales , Estrógenos , Femenino , Gerbillinae , Humanos , Conducta Materna
13.
Pestic Biochem Physiol ; 160: 181-186, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31519253

RESUMEN

Fertility control is considered as the second-generation pest rodent management strategy. Most previous studies have focused on the dosage-dependent effects of quinestrol and levonorgestrel compounds (EP-1) at a ratio of 1:2, but the ratio-dependent effects of EP-1 have not been fully investigated, especially in male rodents. To test the ratio-dependent antifertility effects of EP-1 with different ratios (1:2, 1:1, and 2:1) on male Swiss outbred strain of laboratory mice, forty male mice were randomly assigned into four groups (n = 10). Mice in the three treatment groups were provided one of the three EP-1 mixture compounds for 3 successive days via gavage at a dosage of 50 mg/kg(body weight), and then all mice were sacrificed 15 days after the gavage treatment. Reproductive organ weights, sperm density and motility, levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum and/or testis, and androgen receptor (AR), estrogen receptor α (ERα), estrogen receptor ß (ERß), luteinizing hormone receptor (LHR), and aromatase in testis were determined. Each of the ratios of quinestrol and levonorgestrel significantly decreased the density and motility of sperm and induced atrophy of the epididymis and seminal vesicle. The combination of compounds also significantly reduced serum T and LH levels, increased testicular T levels and decreased testicular estradiol ERß and aromatase levels. EP-1 delivered at a ratio of 1:1 induced the most significant effects on the reproductive parameters assessed and shows the potential for use in fertility control of male rodents.


Asunto(s)
Estrógenos/farmacología , Levonorgestrel/farmacología , Quinestrol/farmacología , Reproducción/efectos de los fármacos , Animales , Aromatasa/metabolismo , Hormonas Esteroides Gonadales/sangre , Masculino , Ratones , Tamaño de los Órganos/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/enzimología , Testículo/metabolismo
14.
J Agric Food Chem ; 67(15): 4160-4169, 2019 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-30900888

RESUMEN

Levonorgestrel (LNG) and quinestrol (QUN) are typical endocrine disruptors that enter the soil via sewage irrigation and sludge return. However, the fates of both compounds in soil are not well-understood. Laboratory microcosm studies were conducted to fill the gap of understanding of LNG and QUN behavior in soils. High values of goodness-of-fit indices (GFIs) were obtained using the double-first-order in parallel (DFOP) model and the single-first-order (SFO) model to fit the degradation kinetics of LNG and QUN in soils, respectively. The end-points (DT50 and DT90) of LNG and QUN were positively correlated with soil total organic carbon (TOC). Soil water content and temperature were observed to be critical factors in degradation of LNG and QUN. The degradation rates of LNG and QUN were very slow under sterile and flooded conditions, indicating that the aerobic microbial degradation was dominant in the degradation of LNG and QUN. Moreover, major transformation products were identified, and biodegradation pathways of LNG and QUN were proposed. The present study is expected to provide basic information for ecological risk assessment of LNG and QUN in the soil compartment.


Asunto(s)
Levonorgestrel/química , Quinestrol/química , Contaminantes del Suelo/química , Suelo/química , Disruptores Endocrinos/química , Inundaciones , Cinética
15.
J Pest Sci (2004) ; 91(1): 157-168, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29367841

RESUMEN

Rodent pest management traditionally relies on some form of lethal control. Developing effective fertility control for pest rodent species could be a major breakthrough particularly in the context of managing rodent population outbreaks. This laboratory-based study is the first to report on the effects of using fertility compounds on an outbreaking rodent pest species found throughout sub-Saharan Africa. Mastomys natalensis were fed bait containing the synthetic steroid hormones quinestrol and levonorgestrel, both singly and in combination, at three concentrations (10, 50, 100 ppm) for 7 days. Consumption of the bait and animal body mass was mostly the same between treatments when analysed by sex, day and treatment. However, a repeated measures ANOVA indicated that quinestrol and quinestrol + levonorgestrel treatments reduced consumption by up to 45%, particularly at the higher concentrations of 50 and 100 ppm. Although there was no clear concentration effect on animal body mass, quinestrol and quinestrol + levonorgestrel lowered body mass by up to 20% compared to the untreated and levonorgestrel treatments. Quinestrol and quinestrol + levonorgestrel reduced the weight of male rat testes, epididymis and seminal vesicles by 60-80%, and sperm concentration and motility were reduced by more than 95%. No weight changes were observed to uterine and ovarian tissue; however, high uterine oedema was observed among all female rats consuming treated bait at 8 and 40 days from trial start. Trials with mate pairing showed there were significant differences in the pregnancy rate with all treatments when compared to the untreated control group of rodents.

16.
Pestic Biochem Physiol ; 143: 122-126, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29183580

RESUMEN

The aim of this study was to assess the effects and reversibility of the synthetic estrogen compound, quinestrol, on the reproductive organs, steroid hormones, and drug-metabolizing enzymes CYP3A4 and CYP1A2 in liver and kidney over time after two quinestrol treatments in female Mongolian gerbils (Meriones unguiculatus). Female gerbils were treated with 4mg/kg quinestrol (9 gerbils/group, 3 treated group) (1 control group, 0mg/kg) for 3days and treated again after 25days. Animals were killed for collection of samples at 5, 10 and 15days after the second treatment ending. Two interval quinestrol treatments significantly increased uterine weight, with trend of increase over time, but no change could be detected in ovarian weights. Quinestrol treatment increased progesterone and estradiol levels, both with trend of decline over time. Quinestrol increased liver and kidney weights and total enzyme content of CYP3A4 and CYP1A2, with trend of decline over time. On the basis of reversible changes of detoxification enzymes or organs, interval quinestrol treatment effectively and reversibly influenced the reproductive hormone and organ to some extent.


Asunto(s)
Estrógenos/farmacología , Quinestrol/farmacología , Animales , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Estradiol/sangre , Femenino , Gerbillinae/sangre , Gerbillinae/metabolismo , Riñón/efectos de los fármacos , Riñón/enzimología , Riñón/patología , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Tamaño de los Órganos/efectos de los fármacos , Ovario/anatomía & histología , Ovario/efectos de los fármacos , Progesterona/sangre , Útero/efectos de los fármacos , Útero/patología
17.
Physiol Behav ; 173: 216-222, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28223035

RESUMEN

Vocalizations are a crucial part of courtship and mating in a wide variety of species. Mating behavior, including courtship calls, is modulated by sex steroid hormones. Male mice produce courtship ultrasonic vocalizations to attract females during heterosexual encounters. However, rare is the knowledge on whether vocal behavior of mice changes under sterilant treatment which will affect gonadal hormone levels. In the present study, we treat male mice with quinestrol, which interferes with the release of the gonadotropin-releasing hormone (GnRH) and has a significant anti-fertility effect in rodents. We compared the differences in the syllable structures (including peak intensity, peak frequency, duration, and bandwidth), total number of calls, and harmonic syllable proportions between quinestrol treated and control male mice. Male mice treated with quinestrol produced more courtship calls and more harmonic syllables than control mice, whereas the parameters of call syllables showed no significant change between the two groups. The results indicate that normal male vocal behavior during sexual interactions could be retained or even reinforced after quinestrol treatment. In addition, female mice approached male mice treated with quinestrol more than control mice, suggesting that the treated male mice were more attractive to the female mice than the controls. Thus, competitive reproductive interference is enhanced. Further, findings provided behavior mechanism in vocal context of the fertility control in mice.


Asunto(s)
Cortejo , Estrógenos/farmacología , Quinestrol/farmacología , Conducta Sexual Animal/efectos de los fármacos , Vocalización Animal/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Femenino , Masculino , Ratones , Espectrografía del Sonido
18.
Integr Zool ; 12(3): 250-259, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27611741

RESUMEN

Fertility control is an alternative strategy to traditional culling for the management of rodent pests. Previous studies have demonstrated that quinestrol is a potential contraceptive for male rodents, but the recovery of fertility in quinestrol-treated rodents has not been evaluated. This study used C57BL/6J mice to evaluate the recovery rate of male fertility after the administration of quinestrol. Diethylstilbestrol (DES), a non-steroid estrogenic compound, was used for comparison. Different groups of mice were treated with 1 mg/kg quinestrol, 1 mg/kg DES, or castor oil separately for 7 days. These mice were then killed on days 8, 22 and 50 respectively. Our results indicated that the weight of epididymides and seminal vesicles decreased significantly on days 8 and 22 in quinestrol/DES-treated mice, with extensive histological changes in the seminiferous tubules. Sperm concentrations in the cauda epididymal fluid were significantly reduced on days 8 and 22 in both quinestrol and DES treatment groups and on day 50 for the DES, but not the quinestrol group. Further analysis revealed that DES-treated mice exhibited a higher proportion of abnormal sperm accumulation in the epididymis, indicating that the normal sperm transportation to the cauda epididymis was blocked. Our results indicate that the anti-fertility effects on male mice given quinestrol were of shorter duration than for those receiving DES at the dose of 1 mg/kg body weight.


Asunto(s)
Dietilestilbestrol/farmacología , Estrógenos/farmacología , Quinestrol/farmacología , Animales , Epidídimo , Fertilidad/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Control de Plagas
19.
Toxicol Mech Methods ; 24(9): 609-15, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25258304

RESUMEN

The pathways involved in quinestrol-induced spermatogenic apoptosis were studied in adult male rat by using daily intragastric administration of 0.01 mg/kg, 0.1 mg/kg and 1 mg/kg body weight quinestrol for two consecutive weeks. The immunohistochemistry staining was performed to measure the expression of proliferating cell nuclear antigen (PCNA), caspase-3, Bax, Bcl-2, Fas and FasL. The results showed that testes weights and the size of seminiferous tubule (ST) decreased as well as the organization of the ST changed significantly after treatment with 1 mg/kg quinestrol. The number of germ cells expressing caspase-3, Bax, Fas and FasL markedly increased whereas the numbers of cells expressing Bcl-2 and PCNA significantly decreased in the group treated with quinestrol at 1 mg/kg compared with the control. The results suggest that quinestrol induced abnormal spermatogenesis through the mitochondrial- and Fas-L-mediated pathways after quinestrol exposure in male rat.


Asunto(s)
Apoptosis/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Mitocondrias/efectos de los fármacos , Quinestrol/farmacología , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Masculino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Sprague-Dawley , Testículo/metabolismo , Testículo/patología
20.
Aquat Toxicol ; 155: 84-90, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24997302

RESUMEN

The occurrence and fate of endocrine disrupting chemicals (EDCs) in aquatic species have attracted close attention during the last decades. In this study, the bioaccumulation and biotransformation of synthetic estrogen quinestrol, one of the typical EDCs, in the plasma and liver of crucian carp, were investigated by a newly developed and validated reversed-phase high performance liquid chromatography with fluorescent detection method. Crucian carp were exposed to quinestrol in concentration of 2, 10, 50, 100 µg/L (5.49, 27.43, 137.17, 274.34 nmol/L) for 60 days. After 60 days' exposure, the concentrations of quinestrol found in liver and plasma were in the range of 0.25-0.69 mg/kg and 0.19-0.30 mg/L respectively, positively correlated with the exposure concentrations ranged 2-100 µg/L (5.49-274.34 nmol/L). There was a negative correlation between the bio-accumulation ratios and the exposure concentrations of quinestrol. 17α-Ethinylestradiol was also found in liver and plasma, and the concentrations were 0.02-0.19 mg/kg and 0.37-0.96 mg/L, respectively. The results indicated that quinestrol can be accumulated and transformed to 17α-ethinylestradiol in crucian carp. Moreover, exposure to quinestrol caused oxidative damages to crucian carp and the content of malondialdehyde increased in all treatment concentrations.


Asunto(s)
Disruptores Endocrinos/metabolismo , Estrógenos/toxicidad , Quinestrol/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Carpas/metabolismo , Relación Dosis-Respuesta a Droga , Estrógenos/administración & dosificación , Estrógenos/metabolismo , Etinilestradiol/metabolismo , Hígado/metabolismo , Malondialdehído/metabolismo , Quinestrol/administración & dosificación , Quinestrol/metabolismo , Contaminantes Químicos del Agua/administración & dosificación , Contaminantes Químicos del Agua/metabolismo
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