Antifertility effects of EP-1 (quinestrol and levonorgestrel) on Pacific rats (Rattus exulans).

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.

Antifertility effects of quinestrol in male lesser bandicoot rat, Bandicota bengalensis, and potential in managing rodent population under field conditions.

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.

Synergistic effects of EP-1 and ivermectin mixture (iEP-1) to control rodents and their ectoparasites.

BACKGROUND: Ectoparasites of rodents play significant roles in disease transmission to humans. Conventional poisoning potentially reduces the population densities of rodents, however, they may increase the ectoparasite loads on the surviving hosts. EP-1 has been shown to have anti-fertility effects on many rodent species, while ivermectin is effective in controlling ectoparasites. In this study, we examined the combined effects of EP-1 and ivermectin mixture (iEP-1) baits on rodents and their corresponding flea/tick loads. RESULTS: In males, the weight of testis, epididymis, and seminiferous vesicle were reduced to less than 33%, 25%, and 17%, respectively, compared to the control group following administration of iEP-1 for 7 days. The weight of the uterus increased by approximately 75%. After 5 days of iEP-1 intake, all ticks were killed, whereas 94% of fleas on mice died after 3 days of bait intake. In the field test near Beijing, the flea index was reduced by more than 90% after 7 days of iEP-1 bait delivery. In a field test in Inner Mongolia, the weights of testis, epididymis, and seminiferous vesicle were significantly reduced by 27%, 32%, and 57%, respectively, 2 weeks after iEP-1 bait delivery. Approximately 36% rodents exhibited obvious uterine oedema accompanied by a weight increase of about 150%. The flea index was reduced by over 90%. CONCLUSION: Our results indicated that iEP-1 is a promising treatment for reducing the abundance of both small rodents and their ectoparasites; this will be effective for managing rodent damage and transmission of rodent-borne diseases associated with fleas and ticks. © 2022 Society of Chemical Industry.

Antifertility effects of levonorgestrel, quinestrol, and their mixture (EP-1) on plateau zokor in the Qinghai-Tibetan Plateau.

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.

Assessment of non-target toxicity effects of synthetic estradiol, quinestrol, in chickens.

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.

Reproductive responses of rice field rats (Rattus argentiventer) following treatment with the contraceptive hormones, quinestrol and levonorgestrol.

The rice field rat, Rattus argentiventer, is a significant pest of rice in Southeast Asia. Fertility control methods have the potential to provide safe and effective alternatives to control methods that often include indiscriminate use of rodenticides or electric barriers. The aim of this laboratory study was to assess uptake of bait coated with different concentrations of the contraceptive hormones, quinestrol (E) and levonorgestrel (P), delivered alone and in combination (i.e. EP-1) and determine the short-term effects on reproductive parameters of adult male and female R. argentiventer. In Experiment 1, 2 concentrations of E, P, and EP-1 (10, 20 ppm) were fed to groups of wild-caught rats for 7 days. In females, both E and EP-1 induced uterine edema. In males, EP-1 reduced epididymis and seminal vesicle weights and lowered sperm motility. However, these responses were inconsistent due to low bait acceptance, especially with increasing concentrations. In Experiment 2, EP-1 (0, 20, 50, 100 ppm) was administered by oral gavage daily for 7 days to male R. argentiventer. There were significant reductions in epididymal and seminal vesicle weights for all oral doses of EP-1, in sperm counts for the 50 ppm dose, and in sperm motility for the 20 and 50 ppm doses compared to the control group. To select the optimum dose of EP-1, we must address the poor acceptance of contraceptive-coated baits by rice field rats. Further research is required to improve the palatability of EP-1 and to test its uptake under field conditions.

The status of fertility control for rodents-recent achievements and future directions.

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.

Anti-fertility effect of levonorgestrel and/or quinestrol on striped field mouse (Apodemus agrarius): evidence from both laboratory and field experiments.

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.

Impact of contraceptive hormones on the reproductive potential of male and female commensal black rats (Rattus rattus).

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.

Ratio-dependent effects of quinestrol and levonorgestrel compounds (EP-1) on reproductive parameters of adult male Swiss mice.

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.

Responses in reproductive organs, steroid hormones and CYP450 enzymes in female Mongolian gerbil (Meriones unguiculatus) over time after quinestrol treatment.

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.

Effects of quinestrol on the vocal behavior of mice during courtship interactions.

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.

Recovery of fertility in quinestrol-treated or diethylstilbestrol-treated mice: Implications for rodent management.

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.

Effects of Simvastatin and Combination of Simvastatin and Nylestriol on Bone Metabolism in Ovariectomized Rats.

We aim to compare the effects of simvastatin and combination of simvastatin and nylestriol on bone metabolism in ovariectomized (OVX) rats. Fifty healthy Wistar female rats were randomly allocated into 5 groups: sham + saline group (group A), OVX + saline group (group B), OVX + simvastatin (5 mg·kg·d) (group C), OVX + nylestriol (0.01 mg·kg·d) (group D), and OVX + simvastatin (3 mg·kg·d) + nylestriol (0.005 mg·kg·d) (group E). All mice were orally administrated with saline or medicine dissolved in saline for 10 weeks. Body weight of rats before and after the experiment was measured. Twenty-four hours after the experiment, calcium (Ca), creatinine (Cr), and hydroxyproline in urine were detected. Serum levels of osteocalcin (bone Gla-protein, BGP) and alkaline phosphatase (ALP) were measured. Bone mineral density was detected and trabecular bone was observed after the isolation of femur and tibia. Remarkably decreased serum BGP and increased serum ALP levels were detected in group B compared with those in group A. However, notably increased serum BGP and decreased serum ALP levels were found in groups C, D, and E compared with those in group B; femoral and tibial bone mineral density decreased in group B compared with that in group A, but increased in groups C, D, and E compared with that in group B. Simvastatin and combination of simvastatin and nylestriol promote formation of new bone, increase bone density, and improve bone microstructure damage in OVX rats.

Mitochondrial- and Fas-L-mediated pathways involved in quinestrol induced spermatogenic apoptosis in adult rat testes.

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.

Quinestrol induces spermatogenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice.

The effects of quinestrol on spermatogenesis were investigated in adult male mice by daily intragastric administration of quinestrol with various doses of 5, 10, 50 and 100mg/kg body weight for 10 days. The sperm counts declined while the number of abnormal spermatozoa went up in mice treated with quinestrol. The testicular weight and seminiferous tubular area gradually declined with increasing dosages of quinestrol to 50 and 100mg/kg. Rarefied germ cells showed irregular distributions in the seminiferous tubules of mice treated with 50 and 100mg/kg quinestrol. Apoptosis was highly pronounced in spermatogonia, spermatocytes, spermatids and Leydig cells. Antioxidant enzyme activities - superoxide dismutase and glutathione peroxidase - as well as total antioxidant capacity significantly reduced, while malondialdehyde contents increased. The number of germ cells expressing caspase-3, p53, Bax and FasL significantly increased whereas cells expressing Bcl-2 significantly decreased in groups treated with 50 and 100mg/kg quinestrol compared with the control. The concentration of nitrogen monoxidum also increased significantly under these dosages. The results suggest that quinestrol stimulates oxidative stress to induce apoptosis in spermatogenic cells through the mitochondrial and death receptor pathways in adult male mice.

Effects of levonorgestrel-quinestrol (EP-1) treatment on Mongolian gerbil wild populations: a case study.

Rodent pest population outbreaks occur frequently in grassland ecosystems in northern China. The Mongolian gerbil (Meriones unguiculatus) is a dominant pest rodent which is distributed across the semi-desert grasslands of Inner Mongolia, China. In 2009, we studied the contraceptive effect of levonorgestrel-quinestrol (EP-1), concentration 50 ppm, on a wild Mongolian gerbil population. The one-off contraceptive treatment was compared with a control group using a semi-monthly live trapping method in the Ordos Semi-desert Grassland Region of Inner Mongolia. The results show that juveniles were not recruited in spring in the treatment group. Ratios of juveniles in the control and treatment groups showed significant semi-monthly differences from spring to summer (one-way ANOVA, F2, 14 = 7.53, P < 0.05). Between both groups, annual fluctuations of juvenile and total population densities were significantly different respectively (F2, 14 = 4.64, P < 0.05; F2, 18 = 7.72, P < 0.05). The contraceptive EP-1 delayed the normal reproductive pattern of Mongolian gerbil populations. This suppressed birth rates of gerbil populations, reduced their densities, and changed their age structures. The period of EP-1 baiting should be extended but it could be an ideal method for controlling Mongolian gerbil populations during each breeding season.

Effects of quinestrol and levonorgestrel on prolactin serum concentration in lactating Mongolian gerbils (Meriones unguiculatus) and reproductive parameters of their offspring.

The effects of the two sterilants, quinestrol (QE) and levonorgestrel (LNG) on serum prolactin (PRL) level in lactating Mongolian gerbils and reproductive parameters of their offspring were examined in the study. Both sterilants increased the serum PRL level in lactating gerbils. The body weight as well as weights of the ovary, testis, epididymides, and seminal vesicles were lower, whereas that of the uterus was higher in the pups originating from QE-treated mothers in comparison to controls. Histological ovarian sections of the offspring from QE-treated mothers contained only growing follicles, whereas their uterine sections showed a thinner endometrium, thicker myometrium, and greater epithelial-cell height than in controls. The histometrical testis characteristics as well as sperm concentration and motility of male pups from QE-treated mothers were lower compared to those of the control group. The serum gonadotropin levels of female pups from mothers treated with QE were lower, whereas the serum estradiol (E(2)) and progesterone (P(4)) levels were higher than in control gerbils. In contrast, serum gonadotropin and testosterone (T) levels of male pups from QE-treated mothers were lower compared to controls. LNG did not affect the examined parameters of the offspring. The offspring from QE-treated mothers was infertile, whereas the offspring from LNG-treated mothers was fertile. In summary, QE and LNG have a stimulatory effect on PRL level in lactating gerbils. It also appears that QE administered via milk to mothers affects reproductive processes of their offspring.

Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus).

The effects of treatment with a combination of levonorgestrel and quinestrol (EP-1; ratio of 2:1) on reproductive hormone levels and the expression of their receptors in female Mongolian gerbils were examined. We show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreased, whereas serum estradiol (E2) and progesterone (P4) increased after EP-1 treatment. EP1 down-regulated mRNA expression of the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor (ER) ßin the ovary. EP-1 up-regulated the mRNA expression of the luteinizing hormone receptor (LHR) and the progesterone receptor (PR) in the ovary as well as ERα and PR in the uterus of Mongolian gerbils. The effects were time-dependent and dose-dependent. EP-1 had no obvious effects on ERα mRNA expression in the ovary. The current study demonstrates that the effect of EP-1 on the expression of ER subtypes is tissue-specific in Mongolian gerbils. EP-1 disrupted the reproductive endocrinology of the Mongolian gerbil. These findings suggest that the effects of EP-1 on reproductive hormone levels and their receptor expression in Mongolian gerbils may be the result of synergistic actions of levonorgestrel and quinestrol, with quinestrol playing the major role.

Subfertile effects of quinestrol and levonorgestrel in male rats.

The contraceptive regimen consisting of levonorgestrel and quinestrol (EP-1) has been shown to be effective in several types of wild rodents. In the present study, we investigated the effect of EP-1 and its two components on fertility and spermatogenesis to elucidate the mechanisms underlying its contraceptive effect. Sprague-Dawley rats were treated with 0.33 mgkg(-1) quinestrol (E group), 0.67 mgkg(-1) levonorgestrel (P group) or their combination (EP group) for 7 days and then killed on Days 21 or 42 after treatment for tissue analysis. On Day 21, the weight of the cauda epididymis decreased significantly, while the weight of the adrenal gland increased significantly in the E and EP groups compared with the weights in the control group. In addition, there was a significant decrease in sperm number in the E and EP groups compared with the control group and there was less staining for the androgen receptor and Wilms' tumour nuclear protein 1 in the E and EP groups. The primary defects in E- or EP-treated rats were abnormal spermiogenesis, lack of elongating spermatids, and pachytene spermatocyte arrest. Analysis of MutL homologue 1 revealed that EP treatment inhibited chromosome recombination during meiosis, but did not cause obvious genetic abnormalities. These data demonstrate that quinestrol, alone or in combination with levonorgestrel, induces subfertility in male rats mainly by interfering with germ cell differentiation. Thus, EP-1 or E alone may be effective contraceptive regimens for fertility control in rodents.