Biomedical subjects

S D Perreault

Publications and source records attributed to S D Perreault.

At least 19 recordsLinked to original sources

PubMed1998

Fertility of rat epididymal sperm after chemically and surgically induced sympathectomy.

Guanethidine, a chemical that selectively blocks sympathetic noradrenergic neurons, was used to investigate the role of sympathetic innervation in the fertility of rat epididymal sperm, using both natural mating and in utero insemination protocols. This animal model correlates, at least in part, with spinal cord injury (SCI) in men. Adult male rats were treated daily by i.p. injections, for 21 or 42 days, with 0 or 6.25 mg/kg guanethidine. To compare the effects of guanethidine-induced sympathectomy with those following surgically induced sympathectomy, the inferior mesenteric ganglion and the proximal hypogastric nerves were removed in another group of rats. Both chemically and surgically induced sympathectomy increased the weight of the epididymis and seminal vesicles/coagulating glands as well as the number and the transit time of cauda epididymal sperm. Neither serum testosterone levels nor LH was affected by treatment with guanethidine. Using natural mating, no litters were produced by guanethidine-treated rats. Chemically denervated rats failed to produce copulatory plugs or ejaculate into the uterus. However, distal cauda epididymal sperm from chemically or surgically denervated rats displayed normal fertilization ability (80%) using in utero inseminations. In addition, the sperm of denervated rats did not show abnormal sperm chromatin structure using an assay that detects DNA damage. We conclude that sympathectomy delays the transit of sperm through the cauda epididymidis and produces ejaculatory dysfunction but does not compromise sperm quality in the distal cauda epididymidis. Moreover, these data provide compelling evidence that there is no association between the prolonged transit time of sperm within the epididymis, i.e., pre-ejaculatory sperm aging, and the fertility of those sperm, which has important implications for artificial insemination using sperm from men with SCI.

Animals↗

PubMed1997

Glutathione oxidation is associated with altered microtubule function and disrupted fertilization in mature hamster oocytes.

We hypothesized that depletion of glutathione (GSH) with diamide, a relatively specific GSH oxidant, may alter the meiotic spindle apparatus in mature hamster oocytes. Immunofluorescent analysis of oocytes exposed to diamide for 1.5 or 3 h revealed time- and concentration-dependent disruption of spindle morphology accompanied by chromosome clumping. In oocytes first cultured in diamide for 1.5 h and then in diamide-free medium for 1.5 or 3 h, microtubules appeared to repolymerize, but normal spindle structure was not regained. HPLC confirmed that diamide oxidized oocyte GSH under conditions identical to those associated with spindle-related abnormalities. Exposure of oocytes to 25 or 50 microM diamide before in vitro fertilization did not affect their ability to undergo fertilization. A significant proportion of the fertilized oocytes that had been exposed to 50 microM diamide before insemination exhibited abnormal multiple female pronuclei with an apparently normal male pronucleus. These observations indicate that mature hamster oocytes are susceptible to oxidative stress during the critical period that precedes fertilization and provide further evidence that GSH plays important roles in oocyte spindle function and pronucleus development.

Animals↗

PubMed1996

Teplice program--the impact of air pollution on human health.

The aim of the Teplice Program is to investigate and assess the impact of air pollution on the health of the population in the district of Teplice, Czech Republic. Characterization of the air pollutants demonstrated unusually high concentrations during winter inversions of fine particles dominated by acidic sulfates, genotoxic organic compounds, and toxic trace elements. The major source of airborne fine particles is the burning of coal for heating and power. Human exposure and biomarker studies demonstrated large seasonal variations in air pollution within the Teplice District and higher seasonal average pollution levels than the comparative district, Prachatice. Personal exposures to fine particles and organic carcinogens [e.g., polycyclic aromatic hydrocarbons (PAH)] were correlated with excretion of PAH metabolites in urine, several trace metals in blood, and DNA adducts in white blood cells. Respiratory and neurobehavioral studies of school children were conducted using questionnaires and clinical measures. A significantly higher prevalence of adverse respiratory symptoms and decreased lung function were found in the Teplice district than in Prachatice. The neurobehavioral studies indicated significantly higher teacher referrals for clinical assessment in Teplice, but the majority of objective performance measures did not differ. Reproductive studies were conducted in both males and females. A study of the effects of exposure on pregnancy and birth found an excess prevalence of low birth weight and premature births in Teplice; these adverse effects were more common in infants conceived in the winter and whose mothers were smokers. Based on questionnaires and medical examination, the reproductive development of young men was not different between districts and seasons, however, measures of semen quality suggest that exposure to high levels of air pollution are associated with transient decrements in semen quality.

Air Pollution↗

PubMed1995

Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II).

Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss in hamsters. Presently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters. Exposure to MBC during either in vivo or in vitro fertilization (IVF) induced identical morphological abnormalities in the maternal chromatin of zygotes and embryos. These abnormalities included either multiple second polar bodies (PB2), and/or multiple small female pronuclei (PN), or meiotic arrest. Multiple PB2, multiple female PN, multiple PB2 with multiple female PN, or meiotic arrest were exhibited by approximately 31%, 15%, 12%, and 2% of the in vivo zygotes; and 3%, 16%, 36%, and 20% of IVF zygotes, respectively. The effects of MBC persisted to day 2 of pregnancy as indicated by decreased (P < 0.05) embryo development to the two-cell stage and the presence of micronuclei in 6% of two-cell embryos from MBC-treated females. Immunofluorescence analysis of microtubules (MTs) confirmed that MBC disrupted spindle MTs during IVF. Numerical chromosome analysis revealed that a single dose of MBC administered during in vivo fertilization induced aneuploidy in the resulting pronuclear-stage zygotes. The present data point to two mechanisms by which peri-fertilization MBC exposure may induce early pregnancy loss: 1) arrested meiosis with no zygotic cleavage; or 2) induction of zygotic aneuploidy with subsequent developmental arrest.

Aneuploidy↗

PubMed1995

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. 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.

Acetates↗

PubMed1993

Optimization of the Hamilton-Thorn computerized sperm motility analysis system for use with rat spermatozoa in toxicological studies.

To optimize the Hamilton-Thorn Motility Analyzer (HTM; Hamilton-Thorn Research, Beverly, MA) for use in reproductive toxicology studies with rat spermatozoa, the accuracy and precision of the instrument were assessed under a variety of instrument settings. Videotapes of both fast- and slow-swimming sperm were analyzed repeatedly to obtain data across a range of sperm velocities as might be encountered as a consequence of exposure to reproductive toxicants. Acquisition rates were varied across the HTM menu choices (30, 19, 10, or 7 frames/sec) as were the number of frames analyzed (5 to 20) at each framing rate. For fast-swimming samples (mean straight-line velocity (VSL) approximately 130 microns/sec) generally good agreement between computer-assisted sperm analysis (CASA) and manually obtained data was found for percentage of motile sperm and straight-line velocity; i.e., CASA values were within 10% of manual values for most frame/rate combinations. The accuracy of these measures held true over a wide range of sperm concentrations and percentage motilities. However, CASA measures were less accurate for sperm samples of lower velocities (mean VSL approximately 50 microns/sec and mean VSL approximately 30 microns/sec) in that the velocity of very slow sperm was overestimated (particularly at 30 frames/sec). A soft-ware change (6.5R) and performing analyses at 19 instead of 30 frames/sec improved straight-line accuracy for the slow sperm and enhanced the discrimination between fast (presumably control) and slow (presumably treated) sperm samples. These data show that this motility analyzer could be successfully configured to evaluate rodent sperm samples. The use of such CASA systems in toxicology studies will provide valuable information that may improve human reproductive risk assessment.

Animals↗

PubMed1993

Influence of the formamidine pesticide chlordimeform on ovulation in the female hamster: dissociable shifts in the luteinizing hormone surge and oocyte release.

The formamidine pesticide chlordimeform (CDF) has been found to interfere with the hormonal control of ovulation in the rat by a presumptive disruption in the catecholaminergic regulation of the midcycle surge of luteinizing hormone (LH). While the brain hypothalamic mechanisms underlying generation of the hamster surge have not been as well-defined, there is evidence for an adrenergic component. The present experiments were designed to investigate the effects of CDF on ovulation in the golden hamster and whether any observed alterations are associated with differences in the appearance of the surge. Intraperitoneal CDF injections (0, 75, 150, or 200 mg/kg) at 1400 hr on proestrus caused a dose-related reduction in oocytes retrieved at 0700 hr on the day of estrus. Additional experiments demonstrated that this effect was due to a delay in ovulation and not a decrease in the complement of oocytes released. Doses of 150 or 200 mg/kg at 1100 hr or 200 mg/kg at 1600 hr were without a comparable ovulatory effect. Characterization of the LH surge indicated that there was a dose-related delay, but that this effect was not sufficient to account for the delay in ovulation. Animals dosed at 1100 hr (150 or 200 mg/kg) exhibited shifts in the surge identical to those animals injected at 1400 hr, but did not show any such detectable effects on the time of oocyte release. CDF administered at 1100 or 1400 hr also caused alterations in serum estradiol and progesterone, even at a relatively low dose of 37.5 mg/kg. The results indicate that CDF given at a time just prior to the preovulatory rise in LH is able to impede ovulation in the hamster by possibly influencing some ovulatory event(s) triggered by the surge. Also, the ability of CDF to alter the timing of LH release is consistent with catecholaminergic participation in the generation of the gonadotropin signal stimulating the final events leading to ovulation. Under the present conditions, this perturbation can be characterized as a delay in the LH trigger, rather than a blockade.

Animals↗

PubMed1992

Utility of light scatter in the morphological analysis of sperm.

We were able to differentiate the morphologically diverse sperm nuclei of four animal species by using an Ortho flow cytometer to detect the forward light scatter from a red (helium-neon) laser. Cytograms depicting the axial light loss and forward red scatter signals revealed unique, but reproducible, sigmoid distributions that reflected not only interspecies differences in shape and size, but variations in particle refractive index and orientation within the flow cell at the time of analysis. Consequently, we were able to use regional gating of the light scatter cytogram to minimize the influence of orientation on the resolution of the fluorescence signal. We also observed that sperm enlarging as a result of chemically induced decondensation exhibit over time a biphasic shift (increase, then decrease) in light scatter at a species-dependent rate. These results suggest that, without any special adaptations to the flow cytometer, light-scatter parameters can be used to discriminate morphologically different sperm, to enhance the resolution of fluorescence measurements that may otherwise be confounded by variability in radial orientation, and to detect alterations in the rate of a biochemical/biophysical process such as decondensation.

Animals↗

PubMed1992

Use of the fungicide carbendazim as a model compound to determine the impact of acute chemical exposure during oocyte maturation and fertilization on pregnancy outcome in the hamster.

Early pregnancy loss due to acute chemical exposure is difficult to detect and essentially impossible to characterize in humans. Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected as a model compound because it would be expected to perturb microtubule-dependent events occurring in the oocyte during meiotic maturation and fertilization. Such effects would likely lead to aneuploidy in the zygote with subsequent early pregnancy loss. Female hamsters were given a single oral dose of carbendazim during meiosis I (the afternoon of proestrus) prior to breeding, or during meiosis II (the morning of estrus) following overnight breeding. Pregnancy outcome was assessed on Day 15 (the afternoon before parturition). When given during during meiosis I, carbendazim treatment (750 or 1000 mg/kg body weight) significantly reduced the percentage of pregnant hamsters. In those animals that became pregnant, the average number of live pups was significantly lower at all dosages of carbendazim used (250, 500, 750, and 1000 mg/kg), an effect attributable to both preimplantation and early postimplantation losses. When given early on the morning of estrus, shortly before and during fertilization (0500 or 0600 hr), carbendazim treatment (1000 mg/kg) produced a similar decrease in litter size. This effect disappeared when carbendazim was administered at a slightly later time (0800 or 0900 hr), after the microtubule-dependent events of fertilization have occurred. These results demonstrate that a single exposure to a microtubule poison such as carbendazim at critical times, coincident with microtubule-dependent meiotic events, can result in very early pregnancy loss. Such loss was readily measurable in this animal model and serves as the basis for further mechanistic studies which would be impossible to conduct in humans.

Abortion, Veterinary↗

PubMed1992

Chromatin remodeling in mammalian zygotes.

With sperm-egg fusion at the time of fertilization the gamete nuclei are remodeled from genetically quiescent structures into pronuclei capable of DNA synthesis. Features of this process that are critical to insure the genetic integrity of the zygote and the success of subsequent embryonic development include: oocyte responses that prevent polyspermy; completion of the 2nd meiotic division by the oocyte; exchange of proteins in the sperm nucleus; and, remodelling of the oocyte chromosomes and sperm nucleus into functional pronuclei. Elucidation of the biological and molecular mechanisms underlying zygote formation and chromatin remodeling should enhance our understanding of the potential vulnerability of the zygote to toxicant-induced damage.

Animals↗

PubMed1992

Methods for assessing rat sperm motility.

Computer-assisted sperm analysis (CASA) systems are becoming more widely used. With this spread of technology come more data from toxicology studies, designed to determine if treatment with putative toxicants affects sperm motion parameters. While these CASA methods provide us with more ways to evaluate toxicity and thus perhaps increase our chances of successfully protecting human health, there is also a greater likelihood that different laboratories will use different methods of collecting data on sperm motility. Different systems used with different methods in different laboratories will inevitably generate data that are difficult to compare. In a prospective attempt to address this issue of comparability and limit the problems, a group of individuals using CASA systems to analyze rat sperm motility convened to discuss methodologic issues, share data, and try to reach a consensus about methods for performing these studies. This article shares those meetings and data in the hope that common methods will enhance interlaboratory comparisons.

Animals↗

PubMed1991

Validation of protocols for assessing early pregnancy failure in the rat: clomiphene citrate.

A battery of protocols for the assessment of maternally mediated toxicity during early pregnancy in the rat is being evaluated for its utility in detecting and defining mechanisms of early pregnancy failure. In this report, clomiphene citrate (CC), an estrogen agonist/antagonist, was used as a model compound in this evaluation process. The protocols involve dosing rats with CC during, and evaluation of multiple endpoints following, (a) the first 8 days of pregnancy; (b) early pseudopregnancy, accompanied by decidual induction; and (c) the pre- and postimplantation intervals of early pregnancy. In addition, the effect of CC on embryo transport rate was assessed. Eight days of dosing with CC during early pregnancy produced a dose-dependent reduction in the number of implantation sites seen on Day 9, concomitant with alterations in maternal hormonal parameters. No effect on the decidual cell response was found, indicating that the mechanism of fertility reduction was not mediated via compromised uterine decidualization. The preimplantation period was highly vulnerable to the toxic effects of CC while no postimplantation resorptions were seen. When embryo transport rate was measured, a statistically significant embryo transport rate acceleration was detected, but this was insufficient to account for all of the observed preimplantation loss. The data suggest an effect of CC on embryo viability, on the embryo's ability to implant, or on the reproductive tract resulting in compromised embryo survival as the potential mechanism(s) mediating CC-induced early pregnancy failure. The battery of protocols was thus successful in identifying CC as a reproductive toxicant and in elucidating the causes of the observed early pregnancy failure.

Animals↗

PubMed1991

Use of bromoergocryptine in the validation of protocols for the assessment of mechanisms of early pregnancy loss in the rat.

Validated protocols for evaluating maternally mediated mechanisms of early pregnancy failure in rodents are needed for use in the risk assessment process. To supplement previous efforts in the validation of a panel of protocols assembled for this purpose, bromoergocryptine (BEC) was used as a model compound because it is known to inhibit pituitary prolactin secretion. BEC was tested using the early pregnancy protocol (EPP), the decidual cell response technique (DCR), the pre- vs postimplantation protocol (PPP), and embryo transport rate analysis (ETRA). These protocols evaluate the effects of chemicals on multiple endpoints following exposure during (a) the first 8 days of pregnancy, (b) early pseudopregnancy accompanied by decidual induction, (c) the pre- and postimplantation intervals of early pregnancy, or (d) the period of embryo transport. In the EPP, dosing with BEC during Days 1-8 of pregnancy reduced the number of implantation sites found on Day 9 as well as serum progesterone. The DCR technique revealed a dose-dependent inhibition of decidual growth concomitant with decreased serum progesterone as a result of BEC treatment. A modified DCR technique using hormone-supplemented ovariectomized rats demonstrated that BEC did not impair decidual growth in the presence of adequate progestogenic support. Pre- vs postimplantation dosing indicated that implantation is vulnerable to BEC effects at least through Day 4. BEC had no effect on embryo transport rate. Data from these protocols identified BEC as having adverse maternal effects during early pregnancy. While the pituitary was not identified by these protocols as the site of BEC's primary action, the protocols did identify a reduction in serum progesterone and impaired uterine function as toxicological mechanisms mediating the reduced fertility seen following BEC exposure.

Abortion, Veterinary↗

PubMed1991

Rat sperm motility analysis: methodologic considerations.

The objective of these studies was to optimize conditions for computer-assisted sperm analysis (CASA) of rat epididymal spermatozoa. Methodologic issues addressed include sample collection technique, sampling region within the epididymis, type of diluent medium used, and sample chamber depth. In addition, sources of variation were identified and accuracy of the analysis was examined. All samples in this report were analyzed using a Hamilton Thorn Motility Analyzer (HTM-2000; Hamilton Thorn Research, Danvers, MA). We found that allowing the sperm to swim out from cuts made in the distal cauda epididymidis yielded samples with percentages of motile sperm 60% higher than samples collected using an aspiration method. Furthermore, sperm isolated from the distal cauda epididymidis exhibited slightly but significantly greater percentages of motile sperm and swimming speeds than sperm isolated from the proximal cauda epididymidis. Of the four motility media examined, all maintained a high percentage of motile sperm over an hour-long incubation period, but Medium 199 and modified Hanks' Balanced Salt supported substantially greater sperm velocity than Dulbecco's Phosphate Buffered Saline (with Ca++ and Mg++), with or without glucose. Motility and velocity endpoints were comparable in 200-, 100-, or 40-micron deep chambers, but significantly lower in 20-micron-deep chambers. Since these and presumably other variables in the preparation and analysis of rat sperm do influence the assessed motility endpoints, it is important to standardize these methods and to consider these issues when interpreting CASA data.

Animals↗

PubMed1991

Thermostability of sperm nuclei assessed by microinjection into hamster oocytes.

Nuclei isolated from spermatozoa of various species (golden hamster, mouse, human, rooster, and the fish tilapia) were heated at 60 degrees-125 degrees C for 20-120 min and then microinjected into hamster oocytes to determine whether they could decondense and develop into pronuclei. Mature, mammalian sperm nuclei, which are stabilized by protamine disulfide bonds, were moderately heat resistant. For example, they remained capable of pronucleus formation even after pretreatment for 30 min at 90 degrees C. Indeed, a temperature of 125 degrees C (steam) was required to inactivate hamster sperm nuclei completely. On the other hand, nuclei of rooster and tilapia spermatozoa and those of immature hamster and mouse spermatozoa, which are not stabilized by protamine disulfide bonds, were sensitive to heating; although some of them decondensed after exposure to 90 degrees C, none formed male pronuclei. Furthermore, nuclei of mature hamster sperm became heat labile when they were pretreated with dithiothreitol to reduce their protamine disulfide bonds. These observations suggest that the thermostability shown by the nuclei of mature spermatozoa of eutherian mammals is related to disulfide cross-linking of sperm protamines.

Animals↗

PubMed1990

Methoxychlor accelerates embryo transport through the rat reproductive tract.

The estrogenic pesticide methoxychlor (MXC) is known to reduce implantation, and, in our previous work, this reduction has been attributed to a direct effect on uterine function. The present study was designed to investigate the effect of MXC on embryo transport rate, another phenomenon that is vulnerable to estrogenic effects. MXC was administered by gavage, at 0, 100, 200, and 500 mg/kg/day, to groups of rats on Days 1-3 of pregnancy (Day 0 = sperm positive), and the distribution of embryos in the oviducts and uteri of animals was assessed at five time intervals prior to implantation. No effect of MXC was detected by the afternoon of Day 1. On Days 2 and 3 of pregnancy, 200 and 500 mg/kg/day MXC were found to accelerate embryo transport into the uterus; the 500 mg/kg/day dosage also reduced the total number of embryos recovered from the tract. On the third day, 100 mg/kg/day MXC also accelerated embryo transport to the uterus and 200 mg/kg/day MXC reduced total embryo recovery. Until the afternoon of Day 3, most control embryos remained in the oviduct. These data demonstrate that MXC produces a dose-dependent acceleration of embryo transport through the female reproductive tract. When compared with previous work, the current data indicate that such an acceleration is the primary cause of MXC-induced preimplantation embryonic loss when exposure occurs after fertilization.

Animals↗

PubMed1990

Acute inhalation exposure to epichlorohydrin transiently decreases rat sperm velocity.

The effect of inhaled epichlorohydrin on rat sperm motility characteristics was evaluated. Male F-344 rats were exposed to 100 ppm epichlorhydrin via inhalation for 4 hr in the morning of Day 0 and killed immediately and on Days 1, 2, 6, and 14 postexposure. Videotapes of cauda epididymal sperm were analyzed (300-350 sperm/sample) with a Hamilton Thorn motility analyzer (HTM-2000, Hamilton Thorn Research, Danvers, MA). Epichlorohydrin did not affect the percentage of motile sperm at any time. However, transient changes in sperm velocity were found. On Day 1 postexposure mean progressive (straight line) and mean path (smoothed curvilinear) velocity were significantly decreased to 80 and 85% of control, respectively. The progressive velocities of sperm from both control and treated rats were normally distributed, indicating a general effect of epichlorohydrin on all sperm as opposed to a more severe effect on a specific sperm subpopulation. Sperm velocity was not significantly affected at later times. Other endpoints (testis and epididymis weights, testicular spermatid counts, and cauda epididymal sperm reserves) were unaltered by epichlorohydrin. Thus, inhaled epichlorohydrin at 100 ppm produced specific, transient decreases in rat sperm velocity. Furthermore, computer-assisted sperm analysis was able to detect these relatively subtle, toxicant-induced changes in rat sperm velocity, demonstrating the utility of this technology in reproductive toxicology studies.

Administration, Inhalation↗

PubMed1990

Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats.

These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, 32, or 48 mg/kg of m-DNB and killed at 14 days post-treatment. Mortality and neurotoxicity were observed at 48 mg/kg, but only in the older animals. Epididymis weight, testicular sperm head counts, cauda sperm reserves, and sperm morphology were affected at 16 and 24 mg/kg and higher in the older and younger animals, respectively. Testis weight and sperm motility were affected at 24 mg/kg and higher in both age groups. Histologic changes included maturation depletion of mid and late spermatids at 16 mg/kg and higher, atrophy of a few to many seminiferous tubules at 24 mg/kg and higher, and immature germ cells in the epididymis. The movement and/or mixing of luminal elements in the epididymis appeared to be influenced by severe testicular effects. In separate groups given only the 48 mg/kg dosage, fertilizing ability was lost by 5-6 weeks post-treatment and several animals failed to recover in 5 months. In the breeder males, minimal to extensive degrees of seminiferous tubule atrophy and sloughed germ cells in the epididymis were still present after 175 days. The studies indicated that the lowest dosage to produce reproductive changes was 16 mg/kg with a no-effect level of 8 mg/kg. A few animals suffered protracted or permanent reproductive damage. Since the older animals were more susceptible to both the general and the reproductive toxicity of m-DNB, the less severe reproductive changes in the younger animals cannot be attributed solely to maturational differences in the testis.

Aging↗