Sperm Count In Rats Research Articles

Safety Evaluation of bioactive Sub-Fraction of Lawsonia inermis Linn leaves in Male Wistar Rats

This study evaluated the safety of bioactive labelled sub-fraction of Lawsonia inermis in male Wistar rats. Twenty male rats ‎were used for this study of five rats per group. Three groups were administered methanol bioactive sub-fraction of Lawsonia ‎inermis at 2.5, 5 and 10 mg/kg for fourteen days while control received distilled water orally. Physiological weight increased in ‎all treatment groups. The group fed with 10 mg/kg had the highest weight gain compared to other treatment groups and the ‎control. Relative organ weight of the heart, liver, kidneys, testes and pancreas did not increase (p>0.05) in all the treatment ‎groups except the pancreas in the group fed with 5 mg/kg that increased significantly (p<0.05). The sperm count in rats fed at ‎dose rate of 10 mg/kg increased significantly (p<0.01) compared to other treatment groups. There were no significant ‎differences in sperm motility, volume and live/dead ratio in the treatment groups compared to control. Haematological ‎parameters such as, PCV, RBC, WBC and haemoglobin concentration were not significantly different compared to control. ‎The AST increased significantly (p<0.01) while urea and creatinine decreased significantly (p<0.001) in group fed with 2.5 ‎mg/kg. 5 mg/kg showed significant reduction (p<0.05) in total protein, urea and ALP while ALT increased significantly. Serum ‎chloride ion at the dose rate of 2.5 mg/kg decreased significantly (p<0.05) when compared with other treatment groups. ‎Sodium ion (Na+) decreased significantly (p<0.01), while Bicarbonates (HCO3-) increased significantly in the 5 mg/kg group. It ‎was concluded that the bioactive sub-fraction of Lawsonia. inermis was safe at the administered dosages.‎

Zinc and selenium supplement mitigated valproic acid-induced testis toxicity by modulating the oxidative redox balance in male rats.

Valproic acid (VPA) is widely used antiepileptic agent which is associated with reproductive toxicity via impairment in oxidative redox. Zinc (Zn) and selenium (Se) are trace element with antioxidant effect that known to be essential for spermatogenesis. In the current study, the protective effect of co-administration of Zn and Se on VPA-induced reproductive toxicity in male rats was evaluated. Forty-eight male rats were divided into 8 groups of six (n=6): Control group (treated with normal saline); VPA only (250, 500, 1,000 mg/kg) group; VPA (500 mg/kg) plus Zn (2 mg/kg) group; VPA (500 mg/kg) plus Se (1.5 mg/kg) group; VPA (500 mg/kg) plus a combination of Zn and Se group; and VPA+vitamin E (20 mg/kg) group. The Animals were sacrificed after 28 days of treatment and sperm analysis was taken. Also, evaluation of oxidative stress markers including malondialdehyde (MDA), protein carbonyl (PC), glutathione (GSH) and histopathological changes were done on testis tissue. Morphological changes and a significant decrease in motility and sperm count in rats treated with VPA were observed. Also, an increase in oxidative stress marker, including MDA and PC and a decrease in GSH level was evident in VPA group. Zn and Se administration was able to protect against sperm abnormality, ameliorate the histological change in testis tissue, and suppressed the increase in oxidative stress markers induced by VPA. These results indicated that combination therapy with Zn and Se showed better an ameliorative effect than each one alone. Therefore, it can be suggested as an effective supplement for reproductive impairment in VPA-treated patient.

Effects of dipyrone and acetylsalicylic acid on contractions of distal cauda epididymis duct, serum testosterone and sperm count in rats.

The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 μM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.

Effects of aqueous leaf extract of Corchorus olitorius on sperm count and sperm motility of adult wistar rats

Background: The plant, Corchorus olitorius is consumed by many tribes and cultures for both nutritional and therapeutic purposes. Purpose: The study was therefore designed to investigate, evaluate and unravel the possible effects of the plant extract on the sperm count and sperm motility. Method: A total number of thirty two adult Wistar rats weighing between 180 and 200 g separated into four groups labeled A,B,C and D respectively were used for the study. Animals in group A which served as the control group were fed with the normal rat chow and water only. The group B rats were administered 100mg/kg body weight of aqueous extract of Corchorus olitorius; while those in group C were administered 500mg/kg body weight of the extract. The group D rats received 1000mg/kg body weight of the extract. For a period of four weeks, the different experimental animal groups received the respective aforementioned treatments once daily, around nine- o’clock in the morning through oral intubation. At the end of the 28 day treatment, the rats were sacrificed and the testes and accompanying epididymis harvested for investigations using standard laboratory standards. Results: Surprisingly, semen analysis showed that group B, C and D rats had an improved and increased sperm motility rate over group (A). Again, there was a pronounced significant increase in the average sperm count of the rats treated with varying doses of Corchorus olitorius leaf extract over that of the control group, a development that appeared to be dose dependent.

Developmental and reproductive toxicity studies of BIA 10-2474

A series of regulatory studies were carried out to investigate the effects of the FAAH inhibitor BIA 10–2474 on fertility, embryo-fetal toxicity and pre- and post-natal development in rats and rabbits. Despite some reductions in sperm count in rats from 50 mg/kg, there were no major changes in male fertility up to 100 mg/kg. In female rats administered up to GD6, there were increases in pre-implantation loss at 50 and 100 mg/kg but neither post-implantation loss nor early embryonic development was affected. In contrast, when administered to female rats during pregnancy (GD6-GD17), BIA 10–2474 at 75 mg/kg/day reduced food consumption resulting in weight loss, increased post-implantation loss and reduced mean fetal body weight. In rabbits, the same maternal toxicity was seen but there were no effects in this species on post-implantation loss or fetal body weights. There were no teratological effects clearly due to BIA 10–2474 and developmental milestones and behavior of offspring were not affected. When administered during pregnancy and lactation (GD6-PND20), some post-implantation loss was seen from 20 mg/kg/day, but developmental milestones and behavior of the offspring were not affected, although males tended to have lower body weight. Based on these data the NOAEL for parental fertility was established as 50 mg/kg/day, the maternal NOAEL during pregnancy was 25 mg/kg/day in rats and developmental NOAEL was 25 and 75 mg/kg/day in rats and rabbits, respectively. When administered during post-natal development to rats the maternal NOAEL was 6 mg/kg/day. The parental reproductive NOAEL, the NOAEL for viability and growth of the F1 offspring, the F1 parental NOAEL and the F1 reproductive NOAEL were all considered to be 20 mg/kg/day.

EDC IMPACT: Reduced sperm counts in rats exposed to human relevant mixtures of endocrine disrupters.

Human semen quality is declining in many parts of the world, but the causes are ill defined. In rodents, impaired sperm production can be seen with early life exposure to certain endocrine-disrupting chemicals, but the effects of combined exposures are not properly investigated. In this study, we examined the effects of early exposure to the painkiller paracetamol and mixtures of human relevant endocrine-disrupting chemicals in rats. One mixture contained four estrogenic compounds; another contained eight anti-androgenic environmental chemicals and a third mixture contained estrogens, anti-androgens and paracetamol. All exposures were administered by oral gavage to time-mated Wistar dams rats (n = 16–20) throughout gestation and lactation. In the postnatal period, testicular histology was affected by the total mixture, and at the end of weaning, male testis weights were significantly increased by paracetamol and the high doses of the total and the anti-androgenic mixture, compared to controls. In all dose groups, epididymal sperm counts were reduced several months after end of exposure, i.e. at 10 months of age. Interestingly, the same pattern of effects was seen for paracetamol as for mixtures with diverse modes of action. Reduced sperm count was seen at a dose level reflecting human therapeutic exposure to paracetamol. Environmental chemical mixtures affected sperm count at the lowest mixture dose indicating an insufficient margin of safety for the most exposed humans. This causes concern for exposure of pregnant women to paracetamol as well as environmental endocrine disrupters.

Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats

Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men.

Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben.

Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben.

Semen characteristics and sperm morphology of Pistia stratiotes Linn. (Araceae) protected male albino rats (Wistar strain) exposed to sodium arsenite

Sodium arsenite has been proven to be abundant in nature and released into the environment through human activities, including agricultural and industrial processes. The objective of our study was to investigate the sperm protective potential of Pistia stratiotes Linn. in arsenic-treated rats. The sperm protective potential of P. stratiotes Linn. (Araceae) was carried out in arsenic-exposed rats using 24 male albino rats (225 to 228 g) aged between 14 and 16 weeks old. They were grouped into 4 (A-D), each group containing 6 rats. Group A animals were orally treated with 100 mg/kg ethanol leaf extract of P. stratiotes Linn. daily for 14 days; group B (sodium arsenite at 2.5 mg/kg body weight; positive control); group C (P. stratiotes extract for 14 days and single dose of sodium arsenite on day 14; group D (0.1 mL propylene glycol; negative control/vehicle). Group B had a significantly lower (p<0.05) percentage sperm motility (26.7±6.67 %) while group A had a significantly (p<0.05) higher mean value (63.3±3.33 %) when compared across the groups. The sperm motility of rats in group D was significantly higher (p<0.05) than groups B and C. This implies that P. stratiotes extract had no adverse effect on sperm motility. The presence of P. stratiotes with sodium arsenite alleviated its harmful effect on sperm motility. The mean value obtained for sperm viability, semen volume and sperm count followed a similar pattern although the difference was not significant (p>0.05) for semen volume and the sperm count of rats across the groups. Total sperm abnormality was 10.44 and 14.27 % with the sodium arsenite treated group having the highest value when compared with groups A treated with P. stratiotes extract and D treated with propylene, although the differences were not significant (p>0.05). The study concluded that ethanol leaf extract of P. stratiotes has no negative effect on sperm motility, viability and morphology and also protected spermatozoa against arsenic-induced reproductive toxicity in Wistar strain albino rats. Therefore, it may play an important role in the protection of populations with chronic sodium arsenite exposure.

Strontium fructose 1, 6-diphosphate alleviate cyclophosphamide-induced oligozoospermia by improving antioxidant and inhibiting testicular apoptosis via FAS/FASL pathway.

This study investigated the treatment effects of a new compound, strontium fructose 1, 6-diphosphate (FDP-Sr), in cyclophosphamide (CP)-induced oligozoospermia. FDP-Sr, with extra high-energy supply, could reverse male hypogonadism in the testis. Male Wistar rats were randomly divided into three groups: control group (vehicle treated), CP group and CP + FDP-Sr group. Both CP group and CP + FDP-Sr groups were orally administered CP (20 mg kg(-1) ) consecutively for the first 7 days to establish CP-induced testicular toxic models. Subsequently, CP group was given orally distilled water per day, whereas CP + FDP-Sr group was received FDP-Sr (200 mg kg(-1) ) for 49 days. Compared to the CP group, the FDP-Sr group showed significantly increased levels of serum testosterone, testis relative weights and epididymal sperm counts in rats. In addition, rats treated by FDP-Sr showed the recuperative activities of testicular marker enzymes and normalised levels of antioxidants in tissue. Testicular protection of FDP-Sr was further demonstrated by enhancing expression of P450scc, reducing ability of FAS/FASL and generating cytoprotection in the histopathological study. FDP-Sr appeared to possess an ability to attenuate CP-induced reproduction toxicity via the activation of antioxidants and steroidogenesis enzymes, and alleviate oligozoospermia via inhibition of testicular apoptosis by FAS/FASL pathway.

The Effect of Eurycoma Longifolia Jack on Spermatogenesis in Estrogen-Treated Rats

INTRODUCTION:There is little data concerning the ability of Eurycoma longifolia Jack (EL) to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats.METHODS:Adult male Sprague-Dawley rats weighing 200–250 g were divided into four groups of six rats each. Group A (control) was given solvent in the same manner as the treated groups were given EL. Group B was treated with EL (8 mg/kg body weight) orally. Group C was treated with estradiol (E2) (intramuscular dose of 500 μg/kg body weight), and group D received a combined treatment of oral EL and intramuscular E2. After fourteen consecutive days of treatment, rats from all groups were sacrificed and subjected to spermatogenic and epididymal sperm cell counts.RESULTS:The spermatogenic cell count in the E2-treated group was significantly decreased as compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). A similar finding was found for the epididymal sperm count; the E2-treated group had a significant decrease in the count compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). Rats that were treated with EL alone exhibited significantly higher sperm counts and sperm motility when compared to the control group (p < 0.05).CONCLUSIONS:EL extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment.

The Effect of Eurycoma longifolia on Sperm Quality of Male Rats

The present study investigated the effects of a standardized methanol extract of E. longifolia Jack containing the major quassinoid constituents of 13alpha(21)-epoxyeurycomanone (1), eurycomanone (2), 13alpha,21-dihydroeurycomanone (3) and eurycomanol (4) on the epididymal spermatozoa profile of normal and Andrographis paniculata induced infertile rats. The standardized MeOH extract at doses of 50, 100 and 200 mg/kg, the EtOAc fraction (70 mg/kg), and standardized MeOH extract at 200 mg/kg co-administered with the EtOAc fraction of A. paniculata at 70 mg/kg were each given orally to male Sprague-Dawley albino rats for 48 consecutive days. The spermatozoa count, morphology, motility, plasma testosterone level and Leydig cell count of the animals were statistically analyzed by ANOVA with a post-hoc Tukey HSD test. The results showed that the sperm count of rats given the standardized MeOH extract alone at doses of 50, 100 and 200 mg/kg were increased by 78.9, 94.3 and 99.2%, respectively when compared with that of control (p < 0.01). The low count, poor motility and abnormal morphology of the spermatozoa induced by the A. paniculata fraction were significantly reversed by the standardized MeOH extract of E. longifolia (p < 0.001). The plasma testosterone level of the rats treated with the standardized MeOH extract at 200 mg/kg was significantly increased (p < 0.01) when compared with that of the control and infertile animals. The spermatocytes in the seminiferous tubules and the Leydig cells appeared normal. Testosterone level was significantly higher in the testes (p < 0.01) than in the plasma after 30 days of oral treatment with the standardized MeOH extract. Interestingly, eurycomanone (2) alone was detected in the rat testis homogenates by HPLC-UV and confirmed by LC/MS, and may have contributed towards the improvement of sperm quality. Thus, the plant may potentially be suitable for the management of male infertility.

Effect of Some Ayurvedic Vajikaran Rasayana Herbs on Heat Induced Testicular Damage in Male Albino Rats

Modern society is phased with a number of environmental and social stressors which may lead to one form of sexual dysfunction or the other. Global warming and exposure to heat is one such phenomenon. A study was conducted to determine the testicular damage in male rats following exposure to high temperatures and the preventive effect of some of Ayurvedic herbs known for their sexual health benefits (Vajikaran) against heat induced testicular damage. Scrotal sacs of male rats were subjected to a 15 min exposure by dipping in water bath maintained at 40± 2 deg C daily for 14 days. The histo-architecture and the overall spermatogenesis profile was considerably prevented in rats treated with lyophilized aqueous extracts of Asparagus racemosus Willd., Chlorophytum borivilianum Sant. F., Curculigo orchioides Gaertn., Dactylorhiza hatagirea (D. Don) Soo and Orchis latifolia Linn.(200 mg/Kg b. w.) as compared to control group animals which were administered vehicle only. The differently treated groups were also subjected to evaluation of sexual behavior. The treatment with extracts results in significant amelioration of sexual behavior and the mount, intromission and ejaculatory latencies were significantly reduced while the frequencies for the same parameter were significantly restored in rats exposed to heat and treated with extracts as compared to heat exposed control group alone. Epididymal sperm count was reduced significantly in heat treated control group animals, whereas the extracts significantly prevented the decrease in sperm count in rats as compared to positive control group, exposed to heat. The results are therefore clear indication of the possible role of these herbs in protecting the genital organs against physical stresses viz. heat.

Evaluation of reproductive safety of β-sitosterol on the American mink ( Neovisonvison)

β-Sitosterol is a weakly estrogenic phytosterol used extensively in functional foods to lower elevated serum cholesterol concentrations due to its inhibitory action on intestinal cholesterol absorption. It caused previously decreased sex steroid concentrations in fish and lowered sperm counts in rats. In the American mink ( Neovison vison), litter size increased slightly due to dietary β-sitosterol supplement. The aim of the present experiment was to conduct a dose–response study on the effects of β-sitosterol on the reproduction of the American mink. Juvenile male and female mink ( n = 480) were exposed to 0, 5, 10 or 50 mg of peroral β-sitosterol kg −1 d −1 for 10 months. After 3 months of exposure in November, 15 males per group were sacrificed and general biochemical variables reflecting overall health were determined. The β-sitosterol-treated male mink had increased absolute and relative masses of intraabdominal fat and higher blood hemoglobin and serum high-density lipoprotein cholesterol concentrations. In spring, the top-rated male mink were mated with multiple females within each study group and reproductive success was assessed. No differences in the reproductive performance of the males (10–11 per group) or females (47–50 per group) could be detected in the exposed groups and the kits of all groups developed in a similar manner. The results suggest that dietary β-sitosterol presents no significant risk to mammalian fertility.

Comparative Toxicity of Five Commonly Used Analgesics on Rat Sperm Count and Sperm Morphology

Comparative Toxicity of Five Commonly Used Analgesics on Rat Sperm Count and Sperm Morphology

Human health effects of dioxins: cancer, reproductive and endocrine system effects

Polychlorinated dioxins, furans and polychlorinated benzene constitute a family of toxic persistent environmental pollutants. In Europe, environmental concentrations increased slowly throughout this century until the late 1980s. Dioxins have been shown to be carcinogenic in animals and humans. In humans, excess risks were observed for all cancers, without any specific cancer predominating. In specific cohorts, excess risks were observed for reproductive cancers (breast female, endometrium, breast male, testis) but, overall, the pattern is inconsistent. In animals, endocrine, reproductive and developmental effects are among the most sensitive to dioxin exposure. Decreased sperm counts in rats and endometriosis in rhesus monkeys occur at concentrations 10 times higher than current human exposure. In humans, results are inconsistent regarding changes in concentrations of reproductive hormones. A modification of the sex ratio at birth was described in Seveso. There exist no data on effects such as endometriosis or time‐to‐pregnancy. Small alterations in thyroid function have occasionally been found. Increased risk for diabetes was seen in Seveso and a herbicide applicators cohort but, overall, results were inconsistent. Experimental data indicate that endocrine and reproductive effects should be among the most sensitive effects in both animals and humans. Epidemiological studies have evaluated only a few of these effects.

Human health effects of dioxins: cancer, reproductive and endocrine system effects.

Polychlorinated dioxins, furans and polychlorinated benzene constitute a family of toxic persistent environmental pollutants. In Europe, environmental concentrations increased slowly throughout this century until the late 1980s. Dioxins have been shown to be carcinogenic in animals and humans. In humans, excess risks were observed for all cancers, without any specific cancer predominating. In specific cohorts, excess risks were observed for reproductive cancers (breast female, endometrium, breast male, testis) but, overall, the pattern is inconsistent. In animals, endocrine, reproductive and developmental effects are among the most sensitive to dioxin exposure. Decreased sperm counts in rats and endometriosis in rhesus monkeys occur at concentrations 10 times higher than current human exposure. In humans, results are inconsistent regarding changes in concentrations of reproductive hormones. A modification of the sex ratio at birth was described in Seveso. There exist no data on effects such as endometriosis or time-to-pregnancy. Small alterations in thyroid function have occasionally been found. Increased risk for diabetes was seen in Seveso and a herbicide applicators cohort but, overall, results were inconsistent. Experimental data indicate that endocrine and reproductive effects should be among the most sensitive effects in both animals and humans. Epidemiological studies have evaluated only a few of these effects.

P-H5-30 The effect of chronic microwave irradiation on the rat sperm count and morphology: Akdag̈.Z 1, Çeli̇K.M.S 1, Ketani̇.M.A 2, Deni̇Z.M 3, Daşdaǧ.S 1 Dept. of Biophysics 1, Histology 2, Anatomy 3 Med.Fac. of Dicle Univ.Diyarbakir (TR)

P-H5-30 The effect of chronic microwave irradiation on the rat sperm count and morphology: Akdag̈.Z 1, Çeli̇K.M.S 1, Ketani̇.M.A 2, Deni̇Z.M 3, Daşdaǧ.S 1 Dept. of Biophysics 1, Histology 2, Anatomy 3 Med.Fac. of Dicle Univ.Diyarbakir (TR)

Dibromoacetic Acid Affects Reproductive Competence and Sperm Quality in the Male Rat

Dibromoacetic Acid Affects Reproductive Competence and Sperm Quality in the Male Rat. Linder, R. E., Klinefelter, G. R., Strader, L, F., Narotsky, M. G., Suarez, J. D., Roberts, N. L, and Perreault, S. D. (1995). Fundam. Appl. Toxicol. 28, 9-17. Recently, we demonstrated with short-duration tests that dibromoacetic acid (DBAA), a commonly occurring by-product of water disinfection, alters sperm morphology and motility in the male rat. These results suggested that the effects of DBAA on sperm quality were likely to compromise reproductive competence of the male rat early in subchronic exposure. The present studies were undertaken to investigate the dose response and time course of alterations in fertility and sperm quality. Proven breeder male rats were gavaged daily with 0, 2, 10, 50, or 250 mg DBAA/kg for up to 79 days; interim and terminal measurements of sperm quality and reproductive outcome were made. Because of the known neurotoxicity of the analogue, dichloroacetic acid, both natural breeding and artificial inseminations were evaluated in untreated females to distinguish between possible behavioral and spermatogenic effects. DBAA compromised male fertility during the second treatment week in naturally bred rats dosed with 250 mg/kg. The early antifertility effect appeared to be the result of behavioral changes since females artificially inseminated with sperm collected on Day 9 successfully produced offspring. However, sperm morphology and motility also were rapidly affected by DBAA treatment so that no offspring via natural insemination and only one litter via artificial insemination were produced subsequent to Day 15. Through 31 days, substantial effects on sperm motility, sperm morphology, and epididymal sperm numbers were observed, but there was no demonstrable effect on serum testosterone or sperm production. Because severe toxicity developed in the group given 250 mg/kg, exposure of these animals was prematurely terminated after 42 doses and their recovery was monitored through a 6-month posttreatment period; decreased testis weights and only limited recovery of reproductive performance were observed. Exposure to 50 mg]kg resulted in moderate changes in sperm morphology and motility and moderate decreases in epididymal sperm counts in rats dosed for 31 or 79 days. However, these males remained fertile, litter size was unaffected, and no paternally mediated developmental defects were noted in their offspring. No effects on sperm quality were detected at dosages of 2 or 10 mg/kg. However, compared to controls, naturally bred DBAA-treated rats tended to have fewer inseminations, fewer copulatory plugs, and fewer multiple litters, suggesting that DBAA may have altered mating behavior at dosages as low as 10 mg/kg.

Dibromoacetic Acid Affects Reproductive Competence and Sperm Quality in the Male Rat

Recently, we demonstrated with short-duration tests that dibromoacetic acid (DBAA), a commonly occurring by-product of water disinfection, alters sperm morphology and motility in the male rat. These results suggested that the effects of DBAA on sperm quality were likely to compromise reproductive competence of the male rat early in subchronic exposure. The present studies were undertaken to investigate the dose response and time course of alterations in fertility and sperm quality. Proven breeder male rats were gavaged daily with 0, 2, 10, 50, or 250 mg DBAA/kg for up to 79 days; interim and terminal measurements of sperm quality and reproductive outcome were made. Because of the known neurotoxicity of the analogue, dichloroacetic acid, both natural breeding and artificial inseminations were evaluated in untreated females to distinguish between possible behavioral and spermatogenic effects. DBAA compromised male fertility during the second treatment week in naturally bred rats dosed with 250 mg/kg. The early antifertility effect appeared to be the result of behavioral changes since females artificially inseminated with sperm collected on Day 9 successfully produced offspring. However, sperm morphology and motility also were rapidly affected by DBAA treatment so that no offspring via natural insemination and only one litter via artificial insemination were produced subsequent to Day 15. Through 31 days, substantial effects on sperm motility, sperm morphology, and epididymal sperm numbers were observed, but there was no demonstrable effect on serum testosterone or sperm production. Because severe toxicity developed in the group given 250 mg/kg, exposure of these animals was prematurely terminated after 42 doses and their recovery was monitored through a 6-month posttreatment period; decreased testis weights and only limited recovery of reproductive performance were observed. Ex posure to 50 mg/kg resulted in moderate changes in sperm morphology and motility and moderate decreases in epididymal sperm counts in rats dosed for 31 or 79 days. However, these males remained fertile, litter size was unaffected, and no paternally mediated developmental defects were noted in their offspring. No effects on sperm quality were detected at dosages of 2 or 10 mg/kg. However, compared to controls, naturally bred DBAA-treated rats tended to have fewer inseminations, fewer copulatory plugs, and fewer multiple litters, suggesting that DBAA may have altered mating behavior at dosages as low as 10 mg/kg.