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Pinealectomy or superior cervical ganglionectomy do not alter reproduction in the wolf (Canis lupus).

Twelve wolves (6 male and 6 female) were used to study the role of the pineal in photoperiodic mediation of seasonal reproduction. Eight wolves were pinealectomized (PNX) or sham-pinealectomized (S-PNX) at 5 mo of age, and 4 were superior cervical ganglionectomized (SCGX) at 16 mo of age (2 males and 2 females per treatment). All attained puberty at the species-typical time, during their second breeding season, except 2 SCGX males that did not survive. Reproductive cycles of an additional male that was SCGX as an adult and the PNX and S-PNX wolves, followed for a minimum of 3 yr, did not differ from each other or from those of unoperated colony wolves on measures of serum testosterone and luteinizing hormone for males, or of serum estradiol and progesterone for females. Nor was the range of dates for ovulation different for treated vs. untreated females. Surgical transection of the olfactory tracts of 1 male and 1 female PNX wolf, inducing anosmia to control for the possibility of pheromonally synchronized cycles, also failed to alter the seasonality of these reproductive parameters. These results do not conform to the model of pineal mediation of sexual cycles for photoperiod-sensitive species. In spite of evidence for photoperiod influence, the wolf apparently relies on a system other than the pineal for seasonal control of reproduction.

Animals

Comparing alternative approaches to establishing regulatory levels for reproductive toxicants: DBCP as a case study.

This paper compares four alternative approaches for deriving regulatory levels for reproductive toxicants by applying them to the available data on the human spermatotoxicant 1,2-dibromo-3-chloropropane (DBCP). The alternatives examined include the Proposition 65 approach (application of a mandatory 1000-fold uncertainty factor to a no-observed-adverse-effect level [NOAEL]), the Environmental Protection Agency (EPA) approach (application of flexible uncertainty factors to a NOAEL), the Benchmark Dose approach (application of flexible uncertainty factors to a dose associated with a known level of change in a reproductive parameter), and the Quantitative Risk Estimation approach (using low-dose linear extrapolation and a model of the relationship between sperm count and infertility). Applied to DBCP, these approaches do not produce substantially different estimates of allowable exposure levels. However, the approaches do have different data requirements and provide different amounts of information on reproductive hazards to risk managers and the public. Neither the Proposition 65 nor the EPA approach provides information about the extent of health risk remaining at a regulatory level. In contrast, the Benchmark Dose approach can provide estimates of the magnitude of sperm count reduction at a regulatory level, and the Quantitative Risk Estimation approach can provide estimates of exposure-induced infertility.

Animals

The effects of uranium on reproduction, gestation, and postnatal survival in mice.

Uranyl acetate dihydrate was tested for its effects on reproduction, gestation, and postnatal survival in Swiss mice. Four groups of animals, each of which consisted of 25 males and 25 females, were administered 0, 5, 10, and 25 mg/kg/day of uranyl acetate dihydrate. Mature male mice were treated orally for 60 days prior to mating with mature virgin female mice treated orally for 14 days prior to mating. Treatment of the females continued throughout mating, gestation, parturition, and nursing of the litters. One-half of the dams in each group were sacrificed on Day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored after 0, 4, and 21 days of lactation. No adverse effects on fertility were evident at the doses employed in this study. Nevertheless, embryolethality could be observed in the 25 mg/kg/day group. Significant increases in the number of dead young per litter were seen at birth and at Day 4 of lactation in the 25 mg/kg/day group. The growth of the offspring was always significantly lower for the uranium-treated animals. However, the present results suggest that uranium does not cause any adverse effects on fertility, general reproductive parameters, or offspring survival at the concentrations usually ingested by man.

Animals

Studies on reproduction in rats with pirmenol, an antiarrhythmic agent.

Fertility and perinatal-postnatal studies were performed in CD rats given pirmenol, an antiarrhythmic agent, at dosages of 0, 25, 50, and 100 mg/kg. The drug was administered orally as diet admixtures in all studies. In the male fertility study, mature male rats were treated for 61 days prior to mating with virgin, untreated female rats. In the female fertility study, mature virgin female rats were treated for 15 days prior to mating with untreated partners with treatment continuing throughout mating, pregnancy, parturition, and weaning of the litters. In both studies, one-half of the dams in each group were killed on Day 21 of pregnancy and the remaining dams were allowed to deliver and wean their offspring and postnatal development was monitored. At weaning, two males and two females were arbitrarily selected from each litter, allowed to mature on unmedicated diet, and then mated within treatment groups to produce the F2 generation. In the perinatal-postnatal study, pregnant females were treated continuously from Day 15 of pregnancy until weaning of the litters on Day 21 postbirth. No adverse effects on fertility, general reproductive parameters, or offspring survival and development were evident at doses employed in these studies.

Animals

Suitability of white-tailed deer as hosts for cattle fever ticks (Acari: Ixodidae).

White-tailed deer (Odocoileus virginianus L.) were evaluated as an alternate host for the cattle fever tick, Boophilus annulatus (Say). The total of adult female ticks recovered and associated reproductive parameters were compared between deer and bovine hosts. Significantly fewer ticks were recovered from deer than from cattle; this was attributed to the grooming behavior of the deer. The mean weight of ticks taken from deer (243.5 mg) was significantly less than that of ticks recovered from cattle (344.5 mg) with about 15% of the ticks from deer prematurely detached. Egg mass weight from the ticks recovered from deer (129.4 mg) was significantly less than that of ticks from cattle (172.1 mg). A significant difference was observed between the percentage hatch of the eggs of ticks from deer (63.1%) and ticks from cattle (76.7%). The index of reproduction was about 20 times greater for the ticks from the cattle than for the ticks from the deer. When the larval progeny of the ticks recovered from deer were reared on cattle, significantly fewer adult females were recovered than when larvae of ticks recovered from cattle were reared on cattle. This indicates a possible reduction in viability. All other parameters were comparable between the two groups. Thus, deer are biologically suitable hosts for B. annulatus, but significantly fewer ticks complete engorgement and those that complete engorgement have reduced fecundity.

Animals

The deleterious effects of cortisol implantation on reproductive function in two species of trout, Salmo trutta L. and Salmo gairdneri Richardson.

Implantation of a cortisol-releasing pellet (60 mg kg-1 fish) into the peritoneal cavity of brown trout, Salmo trutta L. (sexually maturing males and females), and rainbow trout, Salmo gairdneri Richardson (maturing males and immature fish of both sexes), significantly elevated their plasma cortisol level. At 18 days postimplantation, cortisol-implanted sexually maturing male brown trout had smaller gonads, a lower plasma testosterone level, and less gonadotropin in their pituitary gland than control fish. Plasma levels of 11-ketotestosterone and gonadotropin were not significantly affected. Cortisol-implanted sexually maturing female brown trout had smaller gonads, reduced plasma levels of 17 beta-oestradiol, testosterone, and vitellogenin, and a lower pituitary gland gonadotropin content than control fish. The plasma gonadotropin level was unaffected. At 36 days post-implantation, cortisol treatment of maturing male rainbow trout significantly suppressed plasma gonadotropin levels. Plasma levels of testosterone, 11-ketotestosterone, and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, pituitary gonadotropin content, and gonad size were not significantly affected. In sexually immature female rainbow trout, cortisol administration suppressed the level of vitellogenin in the plasma, compared to control-implanted fish. The 17 beta-oestradiol level was not affected. Cortisol implantation did not affect the plasma testosterone level in sexually immature male trout. These results suggest that prolonged elevation of plasma cortisol, to levels well within physiological range, can affect a wide range of reproductive parameters in both brown and rainbow trout. Further, some effects are manifest in immature as well as in mature fish. These findings are discussed in relation to the effects of cortisol treatment on the state of health of the treated fish.

Animals

Testing strategies in behavioral teratology: I. Testing battery approach.

Female rats were given drinking water containing 1.5, 5 or 15 mg/l methylmercury chloride from two weeks prior to pairing until the end of the lactation period. The usual reproduction parameters were recorded. The morphological, functional and behavioral development of the offspring was assessed by subjecting them to a routine testing battery in accordance with the English and Japanese guidelines. Due to toxic effects in the high dose group only offspring of the mid and low dose groups were tested. In both groups some motor coordination and learning deficits as well as delayed sexual maturation were noted, although effects were small and varied considerably. Results demonstrated that a routine testing battery can detect behavioral effects in the offspring at a dose where no reproduction effects are observed.

Animals

The effect of age on reproduction in repeatedly mated female rats.

The effects of age and repeated pregnancies on reproduction were studied in Long-Evans rats. Indices of reproduction measured included estrous cycles, successful mating, numbers of rats producing litters, average litter size, average pup weight and serum LH-from a 4 pm proestrous blood sample. There were no differences in these reproductive parameters between rats with serial pregnancies initiated at 2 or 9 mo of age. The percentage of rats producing normal litters was reduced much faster than the percentage of successfully mated rats with normal ovarian cycles. Although 60% of the rats still had normal ovarian cycles and were mated at 17 mo of age, only one rat (4%) produced a litter. Increasing age and multiple pregnancies did not significantly affect the LH concentration of the proestrous blood sample or the average litter size or pup weight of the rats with successful pregnancies. These data suggest post-ovulatory loss of reproduction in the aging rat.

Animals

The effects of aluminium ingestion on reproduction and postnatal survival in rats.

Aluminium nitrate was tested for its effects on reproduction, gestation, and lactation in Sprague-Dawley rats, at dosages of 0, 180, 360 and 720 mg/kg/day. Mature male rats were treated orally for 60 days prior to mating with mature virgin female rats treated for 14 days prior to mating with treatment continuing throughout mating, gestation, parturition, and weaning of the litters. One-half of the dams in each group were killed on day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored. No adverse effects on fertility or general reproductive parameters were evident at doses employed in these studies. However, the survival ratios were higher for the control group. Moreover, a dose-dependent delay in the growth of the living young could be observed in aluminium treated groups. Therefore, it would seem that high amounts of aluminium should not be ingested during the periods of gestation.

Aluminum

Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats.

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.

Administration, Oral

Reproductive toxicity studies with cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dipalmitate in rats.

cis-(-)-2,3,4,4a,5,9b-Hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dipalmitate (stobadin dipalmitate; in the following briefly called STB) a new prospective cardioprotective drug, was evaluated for effects on fertility, general reproductive performance, prenatal and peri-postnatal development in the rat. Doses of 5, 15 and 50 mg/kg/d were administered orally in aqueous suspension to rats in all studies. Daily treatment of male rats for 70 days before mating and female rats for 14 days before mating and during gestation and lactation had no adverse effects on fertility, survival rate and weight gains of parental animals or on prenatal and postnatal development of pups. There was only evidence of slight adult toxicity late in the experiment, significant increase of anomalous foetuses in both the 15 and 50 mg/kg/d doses and decreased body weight of the young at 50 mg/kg/d on day 21 post partum. Daily oral treatment of pregnant rats with STB throughout organogenesis (day 4 to 16) had no overt effects on dams or on embryo-foetal development, except of increased incidence of some skeletal variations in all treated groups. In the peri-postnatal toxicity study treatment of pregnant dams with STB continuously from day 15 of gestation through parturition and lactation had no adverse effects on reproductive parameters of dams or on survival and development of F1 offspring at any dose used. There were only signs of slight maternal toxicity at 50 mg/kg/d, which consisted of sedated behaviour, reduced liver weight and reversible histopathological changes in kidney tissue. The results of these studies did not reveal serious developmental hazard potentials of STB administered to rats in doses up to 50 mg/kg/d.

Animals

Time of onset of post-partum luteal function and conception in dairy cows.

The following reproductive parameters were studied in 40 Icelandic dairy cows on 2 farms with free stall and tie stall housing: The time of onset of post-partum luteal activity; the time of first post-partum artificial insemination (AI); the time of conception; conception rate to first post-partum AI; the number of AI's per conception; length of gestation; and the number of days between 2 consecutive calvings. Milk for progesterone analysis was sampled 3 times a week from calving until first AI on farm 1, but every day for 90-100 days from calving on farm 2. In this study the average onset of luteal function was 21 days post-partum, the cows were inseminated 62 days and conceived 74 days post-partum. Conception rate to first AI was 71% and number of AI's per conception was 1.6. Significant differences were not found between the 2 farms. The reproductive performance of the cows in this study was greater than found in earlier studies of the Icelandic dairy cows and indicate that this animal has reproductive capabilities comparable to high producing foreign dairy cows.

Animals

Testing strategies in behavioral teratology: IV. Review and general conclusions.

Three laboratories collaborated to evaluate and compare different test concepts to be used for routine testing in behavioral teratology. Rat dams were treated orally with methylmercury starting two weeks prior to pairing until weaning of their offspring. In the first laboratory, the usual reproduction parameters were assessed in the dams, and all offspring (96-103 per group) were subjected to a routine developmental and behavioral test battery. After termination of the tests a random selection of these animals was further tested by multiparametric automated techniques in the other two laboratories. In one of these laboratories 12-13 males and females per group (one of each per litter) were tested in a visual discrimination reversal schedule, using nose-poking as operand. In the other laboratory the free behavioral of eight randomly selected males per dose group was studied in a wheel-shaped activity monitor with respect to locomotion magnitude and structure. In the same laboratory eight other males per group were trained in a discrete trial spatial alternation schedule, using lever press as operand. Both the developmental and behavioral testing battery as well as the automated techniques showed some significant effects in the offspring even at the low dose, where no reproduction effects had been noted. However, whereas the testing battery results were of unspecific nature, results of the automated techniques gave precise and specific information. In order to obtain optimal information, it is proposed to combine both approaches for routine testing. This combination could be achieved by using a balanced testing battery in young pups followed by an appropriate operant conditioning schedule in selected young adults.

Animals

Selection of food allotment for New Zealand white rabbits in developmental toxicity studies.

In three initial studies, female rabbits were fed 125, 150, or 230 g of Purina Certified Rabbit Chow No. 5322 ("regular" chow) per day or 150 g/day of Purina Certified High Fiber Rabbit Chow ("high fiber" chow) for at least 5 weeks prior to artificial insemination and until Day 28 of gestation when fetuses were removed and examined. Animals allotted 230 g/day of regular chow ate approximately 180 g/day and gained more weight than the 150 g/day group until Day 14 of gestation after which food consumption declined and body weight decreased. Animals fed 150 g/day regular chow ate all food provided until after Day 22 of gestation when food consumption decreased dramatically in some animals. Animals in the 125 g/day regular chow and 150 g/day high fiber chow groups ate essentially all food provided throughout gestation. Ad lib feeding in the 230 g/day groups was associated with adverse reproductive consequences consisting of decreased numbers of implants and live fetuses and decreased fetal weight. In one study involving 3 groups fed 125 and 150 g/day regular chow and 150 g/day high fiber chow, reproductive parameters were similar in all 3 groups. However, fetal weight in the 150 g/day regular chow group was 50% more variable than the other groups in association with more variable maternal body weight change late in gestation in that group. In subsequent studies using 125 g/day, there has consistently been fewer animals going off feed late in gestation and a decrease in fetal weight variance of approximately 60% compared to previously when the standard daily allotment was 150 g/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus and preoptic area in rams.

The reproductive effects of placing micro-implants of melatonin in the mediobasal hypothalamus (MBH) and preoptic area (POA) were monitored in Soay rams. Groups of animals were initially conditioned to alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and short days (8L:16D) for at least 9 months to entrain the seasonal reproductive cycle. All experiments were then initiated at 10 weeks under long days when the animals were sexually inactive. In experiment 1, rams were exposed to short days for 14 weeks or maintained on long days to illustrate the photoperiodically induced re-activation and regression of the reproductive axis. In experiments 2-4, rams received micro-implants of melatonin in the MBH or POA, or received control treatments (sham-operated or no surgery) for 12-14 weeks while maintained on long days (total of 12 animals/treatment). The melatonin implants consisted of 22-gauge stainless-steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain. Incubation of the implants in Tricine-buffered saline (pH 8.0) at 37 degrees C showed that the release rate of melatonin was relatively constant after an initial peak in week 1 (means +/- S.E.M.: 3.42 +/- 0.43 micrograms/24 h). Rams with melatonin implants placed in the MBH, but not in the POA, showed a consistently earlier re-activation of the reproductive axis compared with the control animals in all three experiments (12/12 for MBH vs 2/12 for POA). The mean time to maximum testicular diameter was 12.2 +/- 0.9, 21.6 +/- 1.8 and 22.3 +/- 1.2 weeks for the MBH, POA and combined control groups respectively (MBH vs control, P less than 0.01; analysis of variance). The premature growth of the testes in the MBH group was associated with an earlier increase in the blood plasma concentrations of FSH and testosterone, and the appearance of the sexual skin coloration. Removal of the implants resulted in a decline in all reproductive parameters. The melatonin treatments did not cause a detectable increase in the peripheral concentrations of melatonin, or affect the diurnal rhythm in melatonin which reflected the long-day photoperiod. When implants containing 125I-labelled melatonin were introduced into the brain the associated radioactivity was localized to within 1 mm of the implants. The overall results demonstrate that the constant administration of melatonin into the MBH blocks the effect of the endogenous long-day melatonin signal and induces gonadal redevelopment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The effect of repeated mating at short intervals on reproductive performance of gilts.

Three trials involving 87 gilts were completed to investigate the role of additional sexual stimulation on various reproductive parameters. Forty-five gilts were mated twice at 12-h intervals at second pubertal estrus with intact boars beginning 12 h after detection of sexual receptivity (control group). Forty-two gilts were exposed to a vasectomized boar 15 min following each fertile mating to provide additional copulatory stimulus (treatment group). This additional exposure improved (P less than .01) conception rate (100 vs 84%). No statistical differences were observed in number of corpora lutea (CL), number of viable embryos (VE) or number of total embryos (TE) at d 30. These results suggest that additional mating stimuli may have a beneficial effect on conception rate. While the use of additional males resulted in more pregnant females, it likely did not have an effect on litter size.

Animals

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

[Demography and reproduction of Macaca sylvanus in different habitats in Algeria].

Usually described as a cedar forest monkey, the Barbary macaque in effect has colonized a great variety of habitat types. At the moment, it is not known to what extent these different habitats are suitable for the species' survival. We tried to answer this question by comparing the demography of three monkey troops: one lives in a deciduous oak forest; the second lives in an nondeciduous cedar-green oak forest while the third is found on rocky ridges of mountains without any arborescent vegetation. In the three sites, there is a true seasonal breeding season with most births taking place in April to May and most matings occurring in November to December. Details are given on reproduction parameters (sexual activity of females; fertility rates; young survival...). Monkeys densities are higher in cedar forest than in deciduous forest. The smallest density is found on mountain ridges. Forest troops are more numerous, highly stable; their growth rate is better and the population is relatively young. The situation is slightly better still in the cedar forest than in the oak forest with a sex ratio more in favor of females and a better survival of the young. The troop of the mountain ridges is an unstable group ranging from 10 to 25 individuals; the population is aging, with a low birth rate and more male infants surviving compared with females. Demographic differences between sites are discussed according to climate, food availability and human influences (tree-clearing and overgrazing). Conclusions are drawn from this situation, for species conservation.

Algeria