Cauda Epididymal Sperm Motility Research Articles

Cellular Mechanism Underlying Hydrogen Sulfide Mediated Epithelial K+ Secretion in Rat Epididymis.

As a novel gasotransmitter, hydrogen sulfide (H2S) elicits various physiological actions including smooth muscle relaxation and promotion of transepithelial ion transport. However, the pro-secretory function of H2S in the male reproductive system remains largely unclear. The aim of this study is to elucidate the possible roles of H2S in modulating rat epididymal intraluminal ionic microenvironment essential for sperm storage. The results revealed that endogenous H2S-generating enzymes cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) were both expressed in rat epididymis. CBS located predominantly in epithelial cells whilst CSE expressed primarily in smooth muscle cells. The relative expression level of CBS and CSE escalated from caput to cauda regions of epididymis, which was paralleled to the progressively increasing production of endogenous H2S. The effect of H2S on epididymal epithelial ion transportation was investigated using short-circuit current (ISC), measurement of intracellular ion concentration and in vivo rat epididymal microperfusion. Our data showed that H2S induced transepithelial K+ secretion via adenosine triphosphate-sensitive K+ (KATP) channel and large conductance Ca2+-activated K+ (BKCa) channel. Transient receptor potential vanilloid 4 (TRPV4) channel-mediated Ca2+ influx was implicated in the activation of BKCa channel. In vivo studies further demonstrated that H2S promoted K+ secretion in rat epididymal epithelium. Inhibition of endogenous H2S synthesis caused a significant decrease in K+ concentration of cauda epididymal intraluminal fluid. Moreover, our data demonstrated that high extracellular K+ concentration actively depressed the motility of cauda epididymal sperm in a pH-independent manner. Collectively, the present study demonstrated that H2S was vital to the formation of high K+ concentration in epididymal intraluminal fluid by promoting the transepithelial K+ secretion, which might contribute to the maintenance of the cauda epididymal sperm in quiescent dormant state before ejaculation.

Post Exposure Effects of Propoxur (Agricultural Pesticide) on Male Fertility in Wistar Rat

Background: Pesticide toxicity is one of the major environmental health problems for the modern societies, as some of the effects may last long time after exposure. Propoxur is one of the Carbamate pesticide largely used in agriculture in the Western region of Cameroon. Methods: In order to evaluate the post-exposure effects of propoxur, 48 male rats (12 animals per group) aged 30 d were orally gavaged with 0.00, 1.73, 2.60 and 5.20 mg.kg-1 body weight of propoxur for 90 d. At the end of treatment, 6 rats per group were sacrificed and others were followed up for 90 additional days and submitted to a fertility test before sacrifice. Results: At the end of exposure propoxur significantly increased (P<0.05) the testis weight while it decreased (P<0.05) the cauda epididymal sperm motility in rat. Propoxur treatment and post-treatment exposure showed variable effect on the fertility rate with an increase and decrease at 2.60 and 5.20 mg.kg-1, respectively. At the 90th day post treatment, there was a significant decrease (P<0.05) in epididymis weight and sperm count and motility (P<0.05). In addition, post-exposure treatment with propoxur reduced (P<0.05) the pup litter size and the sex ratio at all doses. Histopathological examination revealed a high vacuity of germinal epithelia in treated rats that persisted after post-exposure time. Conclusion: Propoxur negatively affected male rats’ reproductive parameters with more significant adverse effects observed 90 d after the end of exposure.

Antifertility Activity of Ethanolic Seed Extract of Celery ( Apium Graveolens L. ) in Male Albino Rats

Objectives:This study was aimed at evaluating the effect of ethanolic seed extract of Apium graveolens L. (Apiaceae)(ESEAG) on male rat fertility.Methods:Two doses of the extract (425 and 213 mg/kg body weight) were administered by oral gavage for sixty consecutive days. Five days before the end of this period, each rat was cohabited with two female rats. Fertility indices, hematology, and organ weight and histology were then assessed. Results:The ESEAG arrested spermatogenesis and caused a marked, dose-dependent decrease in sperm count, cauda epididymal sperm motility, blood testosterone concentration, weight of testes and seminal vesicles, testicular protein contentas well as diameter and viability of seminiferous tubules.In addition, a lower number and weight of viable fetuses was obtained for female rats which were impregnated by ESEAG-treated male rats. Hematological parameters, serum liver enzyme levels, thyroid weight and liver and kidney histoarchitecture were not affected. Conclusion:This study shows a dose-dependent antifertility effect of the ESEAG in male rats without toxic effects on other body organs.

Caprine cauda epididymal sperm motility pattern in the capacitation medium supplemented with leptin

Leptin is an adipocyte-derived hormone with a role in the reproductive system through metabolic signals. Studies have suggested that binding of leptin to its receptors which have been found in human and boar sperm activates biochemical pathways leading to sperm capacitation. The present study was designed to explore the effects of leptin on sperm kinetic pattern during capacitation in vitro. Epididymal spermatozoa were obtained from 30 adult goat testes in six replicates and incubated in capacitation medium (Ca2+-free Tyrode’s medium, Sperm-TALP) supplemented with 0 (Con, control group), 10 and 100 ng/mL (L10 and L100 groups, respectively). Motion parameters were assessed using computer-assisted sperm analysis system at 10, 30, 60, 120 and 240 min after sperm incubation at 37°C and 6 % CO2. Exposure of spermatozoa to two different doses of leptin caused a significant increase (p < 0.05) in total and progressive sperm motility, curvilinear and straight line velocity, linearity (Lin), mean angular displacement, amplitude of lateral head displacement (ALH) and beat cross-frequency (BCF) compared to the control group specially up to 60 min. There was not any significant difference between L10 and L100 groups in the evaluated parameters except for the first 10 min that L100 had better result in increasing Lin, ALH and BCF (p < 0.05) and at the time of 240 min in which L10 showed a significant increase in all motion parameters. In conclusion, this study showed that leptin supplementation had significant effects on sperm motility patterns and so could enhance the sperm capacitation process.

Lack of effects for dietary exposure of bisphenol A during &lt;i&gt;in utero&lt;/i&gt; and lactational periods on reproductive development in rat offspring

The potential for health effects on humans with exposure to bisphenol A (BPA) has raised concerns, and the adverse effects of low-dose exposure to BPA on reproduction have been controversial. The purpose of the present study was to investigate the effects of low-dose exposure to BPA on reproductive development in F(1) rat offspring. Pregnant female Sprague-Dawley rats (F(0)) were fed a diet containing low doses of BPA (0, 0.33, 3.3, or 33 ppm) from gestational day (GD) 6 through postnatal day (PND) 21. The weanlings (F(1)) from all dose groups were fed a normal diet ad libitum after weaning and then were subjected to necropsy at 5 weeks or 3 months of age. No BPA-related changes were observed in body weight or weight of any of the major reproductive organs in F(1) males and females. Epididymis weight was significantly lower only in 3-month-old F(1) males exposed to 33 ppm BPA. Anogenital distance (AGD), the ratio of AGD to the cube root of body weight, and relative ovary weight were significantly lower in 5-week-old F(1) females exposed to 3.3 and 33 ppm BPA, but significant differences were not observed in 3-month-old females. There were no BPA-related effects on cauda epididymal sperm motility in 3-month-old F(1) males. Plasma reproductive steroid hormone concentrations were not altered among groups in either sex. These outcomes indicate that low-dose exposure to BPA in the diet does not adversely affect reproductive development in F(1) rat offspring.

Reversible contraceptive efficacy and safety evaluation of withanolide A from Withania somnifera in male albino rats

Background The present investigation elucidated the association of biological activities with specific secondary metabolites known as withanolide present in the Withania somnifera. The aim of present study was to evaluate safety and reversible contraceptive efficacy of alkaloids from this plant to search for an inexpensive, orally effective and reversible male contraceptive. Study design Withanolide A (10 mg/kg/body wt/day per oral dose) was administrated orally to male albino rats daily for 60 days. A marked dose-dependent decrease in the count and motility of sperm of treated rats was observed, compared with controls in a randomized controlled study. Results This plant-based contraceptive inhibited male fertility, after administration of (10 mg/kg body weight) withanolide A from W. somnifera. A marked reduction in counts and motility of cauda epididymal sperm in a dose-dependent manner was observed in the treatment group, but after 30 days withdrawal of treatment, all these changes were reversibly observed in the recovery group. Conclusions The oral administration of 10 mg/kg/body wt/day of withanolide A ( W. somnifera) in male albino rats produced a reversible antifertility effect.

Assessment of early sexual maturity in nondescript local pigs of northeast India: Testicular development, spermiogram and in vivo pregnancy

The tribal population of North Eastern India follow a unique practice of mating the sow with a male pig from its own litter to avoid maintenance of boar for breeding. In this system, it is claimed that the nondescript local male pigs, at very young age (around 3 months), impregnate the sow. There is no documented report available on this practice. The present study, therefore, was carried out to study the testicular development and early sexual maturity in nondescript local pigs and to compare with Hampshire and Large White Yorkshire (LWY) pigs. The weight and circumference of the testes were significantly ( p < 0.05) higher in nondescript local pigs compared to Hampshire and LWY pigs, but the testicular length did not differ significantly. The epididymis weight and length of different segments also did not differ significantly between Hampshire and LWY pigs. However, the nondescript local pigs had significantly heavier ( p < 0.05) epididymal weights at four and six months of age relative to the other two breeds. The testicular tissue per kg body weight was significantly higher ( p < 0.05) in nondescript local pigs than the Hampshire and LWY pigs. The progressive motility of cauda epididymal sperm was 30.5 ± 5.6 and 70.5 ± 4.8% at two and three months of age, respectively while the corresponding live percent were 57.9 ± 7.2 and 82.6 ± 6.4 in nondescript local pigs. The nondescript local male pigs could mate and impregnate the females as early as 108.8 ± 8.0 days of age. It was inferred that the testicular growth was faster in nondescript local pigs compared to Hampshire and LWY pigs and the nondescript local male pigs have the capacity to mate and impregnate sows at 3–4 months of age.

Sonic Hedgehog Pathway Inhibition Alters Epididymal Function as Assessed by the Development of Sperm Motility

The sonic hedgehog (Shh) signaling pathway plays a role in pattern orientation in the developing embryo and has been shown to be required for development of the prostate and external genitalia. Recent evidence has shown that important elements of the Shh pathway are also expressed in the adult mouse epididymis at both the gene and protein levels. The objective of the present investigation was to refine the expression pattern of Shh in the mouse epididymis and to determine if the Shh pathway is important for epididymal function vis-à-vis sperm maturation. The former was achieved by microarray analysis of Shh expression in all segments of the mouse epididymis, and the latter was determined by 14-day administration of cyclopamine, a Shh pathway inhibitor, followed by a microassay for the activation and duration of cauda epididymal sperm motility. Shh pathway inhibition was monitored by semiquantitative reverse transcriptase-polymerase chain reaction for expression of epididymal Gli1 and Gli3. The Gli family of transcription factors is commonly activated and regulated by Shh pathway activation. Cyclopamine treatment reduced Gli1 expression by 61% and initiation of cauda sperm motility by 50%. Gli3 expression was reduced by approximately 50%. Subsequent cluster analysis using the microarray data on epididymal gene expression highlighted several potential target genes for the Shh pathway, the most prominent of which is prostaglandin D2 synthase. These results indicate that an operating Shh pathway is important in the murine epididymis for the development of sperm motility and implies a role for Shh signaling in adult epididymal function.

Toxicological effects ofCarica papaya seed extract on spermatozoa of mice

Investigations were carried out on epididymal spermatozoa of male mice to study the effects of high dosages (100, 200 and 300 mg kg(-1) bwt) of aqueous Carica papaya seed extract. The results revealed a significant dosedependent suppression of cauda epididymal sperm motility coinciding with a decrease in sperm count and viability. When tested 45 days after the withdrawal of treatment, complete normalcy was restored, proving that the induced effects were transient.

Radiation exposure exerts its adverse effects on sperm maturation through estrogen-induced hypothalamohypophyseal axis inhibition in rats

Irradiation has adverse effects on reproductive aspects such as spermatogenic cell population and cell malformation, leading to reduced sperm count and non-viable spermatozoa. This has overshadowed possible effects of radiation exposure on biochemical environment throughout the epididymis and the viability of spermatozoa that appeared morphologically normal. The effects of radiation exposure on sperm quality were evaluated through mating trials and assessment of the cauda epididymal sperm motility. Sprague Dawley rats with body mass of 300–400 g were selected at random. Two experimental groups received acute 6°Co γ-radiation doses of 3.5 and 6.0 Gy, respectively. Data were collected 2, 7, 14, 21, 28 and 35 days post-irradiation. Each male was housed with a non-irradiated super-ovulated female during mating trials. Cauda epididymal sperm motility was assessed with the CASMA. Hormone analyses were carried through chemiluminescence diagnostic tests to determine the endocrine status. Results suggest that irradiation causes an overproduction of estrogens, which suppresses the hypothalamic-pituitary axis and inhibits LH and FSH secretions. Both LH and FSH deficiencies have negative effects on the testicular index and local reproductive hormones. Elevated estrogen levels influenced the epididymal internal milieu negatively, resulting in rigid, flagella bending sperm tail, impaired progressive movement of the spermatozoa and hence infertility

Bromochloroacetic acid exerts qualitative effects on rat sperm: implications for a novel biomarker.

Disubstituted haloacid by-products of drinking water disinfection such as dibromoacetic acid and dichloroacetic acid have been shown to perturb spermatogenesis and fertility in adult male rats. In the present study we sought to establish whether equimolar exposure to bromochloroacetic acid (BCA), a prevalent by-product in finished drinking water, is also capable of disrupting these endpoints, and if so to determine whether the novel biomarker of fertility (SP22) would be correlated with subfertility induced by testicular toxicity. A dose range finding study indicated that body weight was not affected by exposure to 14 daily doses of 72 mg/kg BCA while numerous male reproductive parameters were altered, including decreases in the number and progressive motility of cauda epididymal sperm. In addition, there was an increased incidence of delayed spermiation in the testes of males exposed to 72 mg/kg BCA. In the definitive study, exposures ranged from 8 to 72 mg/kg, the fertility of cauda epididymal sperm was evaluated by in utero insemination, and the two-dimensional profile of cauda sperm membrane proteins was evaluated quantitatively. The morphology of both caput and cauda epididymal sperm was altered by 72 mg/kg BCA. The fertility of cauda epididymal sperm, the percentages of progressively motile sperm and progressive tracks, and two sperm membrane proteins (SP22 and SP9) were decreased significantly by each BCA exposure. While the two sperm proteins and the two measures of progressive motility were each significantly correlated with fertility, only one of these measures (i.e., SP22) had an r value of greater than 0.5. When data for SP22 and fertility were fit to a nonlinear model, r(2) was 0.84. Using this exposure paradigm, the no-observed-effect level for BCA is less than 8 mg/kg. Moreover, SP22 may be useful in predicting compromised fertility after exposure to by-products of drinking water disinfection.

Antispermatogenic Effects of an Ethanol Extract of Citrullus colocynthis Root in Male Albino Rats

A crude 50% ethanol extract of Citrullus colocynthis Schrad roots was administered orally to male albino rats at dose levels of 50, 100 and 200 mg/kg b.wt./day for a period of 60 days for evaluation of antifertility effects. Significant decreases in cauda epididymal sperm motility, density, number of pups and fertility were observed in all treatment groups. A marked reduction in the weight of testes, epididymis and seminal vesicle was observed. The weight of the ventral prostate was nonsignificantly decreased. The histoarchitecture of testis revealed degenerative changes in the seminiferous epithelium, arrest of spermatogenesis at the stage of round spermatid, cytolysis and lumen filled with eosinophilic material. Seminiferous tubule diameter and Leydig cell nuclear diameter were decreased. A marked alteration in the Leydig cell differential counts was also noticed. The Sertoli cell nuclear diameter was unchanged. The concentration of cholesterol in testis, fructose in seminal vesicle and protein and sialic acid in all reproductive sex organs were depleted. Serum testosterone levels were markedly decreased in all treatment groups. In conclusion, a 50% ethanol extract of C. colocynthis roots produced antifertility activity in male albino rats.

Addition of specific metabolites to bovine epididymal cell culture medium enhances survival and motility of cryopreserved sperm.

We have developed a cell culture system of bovine epididymal epithelium in which cryopreserved bovine sperm motility was efficiently maintained for many hours. The culture conditions to maintain viable epididymal cells are quite different from conditions normally used to incubate sperm cells. Thus, we have modified a previously described principal cell medium (PCM; Moore et al, 1992) using HEPES as a buffer and supplemented media with myo-inositol, pyruvate, lactate, glycerol, and carnitine to mimic epididymal intraluminal conditions. In the first experiments the effects of PCM and our epididymal cell medium (ECM) on sperm motility were compared in the absence of cells and evaluated by microscopic analysis under a phase contrast microscope or using the Hamilton Thorn Image Analyzer System. Our results showed that motility of cauda epididymal sperm was significantly higher in ECM than in PCM during a 48-hour incubation period when both media were supplemented with 10% fetal bovine serum (FBS). We then replaced FBS with bovine serum albumin (BSA) or no proteins at all to verify if ECM was able to enhance sperm survival. To test this aspect we used frozen-thawed sperm, which survived up to 48 hours when sperm cells were coincubated with epididymal cell monolayers. Hence, PCM, ECM, and different media containing each metabolite of ECM were supplemented with 0.5% BSA to assess motility of thawed sperm after an incubation period of 6 hours. A positive effect on sperm motility was observed in all fresh and unconditioned media containing 1 mM pyruvate. Motion parameters were more efficiently maintained in all conditioned media than in unconditioned media. Our results showed, however, that pyruvate was almost completely oxidized or consumed by epididymal cells during preincubation of culture media. We conclude that motility of frozen-thawed bovine spermatozoa can be improved using a culture medium or a medium conditioned by epididymal cell cultures without carnitine but containing mainly pyruvate, inositol, glycerol, and lactate.

Sterility due to inhibition of sperm motility by oral administration of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats.

The contraceptive effects of benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya have been reported in male albino rats at the dose regimens 5 and 10 mg/animal/day; oral for 150 days. The body weight, weight of testis, epididymis, seminal vesicle and ventral prostate remained unaltered during the entire course of the investigation. Total suppression of cauda epididymal sperm motility coincided with a decrease in sperm count, viability and an increase in per cent abnormal spermatozoa during 60-150 days observation period. Minor changes in the germ cell proliferations in the testis and vacuolization and pyknotic nuclei in the few epithelial cells of the cauda epididymis were observed. Histology and biochemical composition of testis and accessory sex organs, haematology and serum clinical biochemistry and serum testosterone levels remained unchanged throughout the course of the investigation. Test for estrogenicity indicated mild estrogenicity. Monthly fertility test showed negative fertility. All the altered parameters returned to normal level following 60 days withdrawal of the treatment. The results suggest that the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya exerts antifertility effects in rats without adverse toxicity and that the effects may be directly rendered on the spermatozoa.

Effects of ethanol ingestion on epididymal glycosidases and fertility in the rat.

Epididymal glycosidases play a role in sperm maturation by modifying sperm surface glycoproteins. To study the effects of ethanol on epididymal sperm maturation, ethanol (3 g/kg body weight as 25%, v/v) was administered to a group of rats by gastric-intubation twice daily for 30 days. In another group, rats were also treated with alcohol for 30 days but were then withdrawn from treatment for 30 days to assess the reversibility of ethanol-induced effects. Ethanol-induced changes in epididymal tissue and sperm glycosidases, cauda epididymal sperm motility and the fertility of rats were assessed. Ethanol treatment caused a marked decrease in the specific activities of glycosidases in both tissues and spermatozoa from epididymal segments. Cauda epididymal sperm motility and the fertility of ethanol-treated rats were significantly impaired compared to control rats fed an isocaloric diet. These changes are likely to be the consequence of direct and indirect effects of ethanol mediated through subnormal testosterone and dihydrotestosterone. Most of these changes were found to be reversible. The present study suggests that impaired activity of sperm glycosidases may be one of the factors responsible for defective sperm motility and fertilizing potential in ethanol-treated rats.

Rat epididymal sperm quantity, quality, and transit time after guanethidine-induced sympathectomy.

Guanethidine, a chemical that selectively abolishes peripheral noradrenergic nerves, was used to investigate the role of sympathetic innervation in the maintenance of epididymal sperm quantity and quality. Four groups of 10 adult male rats each were treated daily for 21 days, by i.p. injections, with either 0 (saline vehicle), 6.25, 12.5, or 25 mg/kg guanethidine. Norepinephrine content was reduced to undetectable levels in the cauda epididymidis in all guanethidine groups after 3 wk of treatment and was reduced to 7.4% of the control values after 1 wk of 6.25 mg/kg treatment. While body weight gain was significantly decreased at 12.5 and 25 mg/kg compared to that in controls, there was a significant increase in the weights of the seminal vesicles/coagulating glands in all treated groups. The number of homogenization-resistant spermatids per testis and the daily sperm production per testis remained unchanged. The weight of the epididymis was significantly increased at 6.25 and 12.5 mg/kg. Moreover, the number of cauda epididymal sperm and the transit time were increased significantly at 6.25 mg/kg (10.2 days) compared to values in the control cauda (6.3 days). Neither serum testosterone levels nor LH was affected in a dosage-related manner. There were no effects of guanethidine treatment on cauda epididymal sperm motility or morphology. A quantitative analysis of detergent-extracted cauda epididymal sperm proteins by SDS-PAGE revealed no differences, but there were diminutions in seven proteins in homogenates of caput/corpus tissue. Histologic analysis of testis and epididymis sections revealed no differences between control and denervated animals. In a subsequent experiment the lowest effective dosage (6.25 mg/kg) was given to rats for 1 wk, and an increased number of cauda epididymal sperm and a delay in sperm transit were observed. Our results indicate that low-dosage guanethidine exposure denervates the epididymis within 1 wk, thereby delaying epididymal transit; however, neither 1- nor 3-wk exposure produces qualitative changes in the sperm.

Contraceptive efficacy of Carica papaya seed extract in male mice (Mus musculus)

AbstractThe effects of an aqueous extract of Carica papaya seeds (20 mg/kg body weight/animal/day orally and 5 mg/kg body weight/animal/day i.m. for 60 days) were investigated for contraceptive efficacy and other related side effects in male albino mice, Mus musculus. The data revealed that the extract might be causing an androgen deprived effect to target organs resulting in alterations in the internal milieu of the cauda epididymis especially. The treatment did not, however, affect the testicular sperm count suggesting that it acted at the post‐testicular level which lead to a reduction of cauda epididymal sperm motility and thus the treatment brought about a significant reduction in fertility rate. The induced effects were transient and reversible upon withdrawal of the treatment, elucidating that functional sterility could be induced by the aqueous papaya seed extract in rodents.

Antifertility Effects of Aqueous Extract ofCarica papayaSeeds in Male Rats

The influence of the crude aqueous extract of Carica papaya L. (Caricaceae) seeds has been studied on semen profile, fertility, body and organ weight response, and toxicology in male albino rats. The extract was administered at the dose regimens of 10 and 50 mg/animal/day orally for 30, 60, and 90 days and 0.1 and 1.0 mg/animal/day intramuscularly for 15 and 30 days. Cauda epididymal sperm motility and count was reduced significantly at low and high dose regimens both in the oral as well as the intramuscular groups. The reduced sperm motility was associated with morphological defects. Testicular sperm counts were also reduced in all the treatment groups except the low dose intramuscular group. Fertility tests showed dose- and duration-dependent reduction and zero fertility was observed at high dose regimens of the oral and intramuscular groups following 60 and 30 days of treatment, respectively. Testicular weight was reduced in all the treatment groups, whereas accessory sex organs showed a variable response. Body weight and toxicological observations did not show any untoward response. Fertility and all other associated changes returned to normal within 45 and 30 days of treatment cessation in the oral and intramuscular groups, respectively. The data revealed that reversible sterility could be induced in male rats by papaya seeds aqueous extract treatment without adverse effects on libido and toxicological profile.

Induction of Reversible Antifertility with a Crude Ethanol Extract ofCarica papayaSeeds in Albino Male Rats

AbstractA crude ethanol extract of Carica papaya L. seeds was administered to male albino rats at dose regimens of 10 and 50 mg/animal/day orally for 30, 60 and 90 days and 0.1 and 1.0 mg/animal/day intramuscularly for 15 and 30 days for the evaluation of contraceptive efficacy, reversibility and related side effects. Significant decreases in cauda epididymal sperm motility, sperm count, fertility and litter size were observed after oral dosing of the extract, while intramuscular administration caused significant decreases in cauda epididymal sperm motility and litter size. Testis weight decreased significantly after oral, but not intramuscular, administration. Body weight response, hematological parameters and blood/serum biochemical parameters were comparable to control values throughout the experimental period. Complete recovery of all the altered parameters except sperm motility in the high dose intramuscular group was evident following 60 and 45 days of treatment withdrawal in animals dosed orally an...

Reproductive effects of diethylene glycol and diethylene glycol monoethyl ether in Swiss CD-1 mice assessed by a continuous breeding protocol

Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) were evaluated for reproductive toxicity in CD-1 mice using a continuous breeding protocol. Compounds were administered in the drinking water at 0, 0.35, 1.75, and 3.5% w v (DEG) or 0, 0.25, 1.25, and 2.5% w v (DEGEE). Exposure of the breeding pairs to 3.5% DEG for 14 weeks produced statistically significant decreases in the number of litters per pair, live pups per litter, proportion of pups born alive, and live pup weight. There was also a significant increase in the cumulative days to litter and a significant decrease in the number of pairs producing the third, fourth, and fifth litters for the 3.5% DEG-exposed mice. A crossover mating trial of the F 0 mice to determine the affected sex was inconclusive, but suggested that offspring development was compromised in females exposed to 3.5% DEG. Slight maternal (F 0) toxicity was noted for the 3.5% DEG group (7% decrease in body weight). The F 1 generation, at 3.5% DEG, had decreased body weights at birth and exhibited poor postnatal survival. At the intermediate dose of DEG, body weights of both sexes were depressed at weaning, at onset of mating, and at necropsy. However, no adverse effects on reproduction were observed. DEGEE had no effect on reproduction in the F 0 or F 1 generation mice despite a 34% decrease in cauda epididymal sperm motility in the F 1 males at 2.5% DEGEE. Other signs of toxicity observed in these F 1 mice included increased relative liver weights. These data indicate that DEG is a reproductive toxicant in Swiss mice affecting fertility and reproductive performance, albeit at high doses (equivalent to 6.1 g/kg/day). However, its monoethyl derivative, DEGEE, is without adverse effects on fertility and reproductive performance.