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Role of daylength in the regulation of reproductive function in the male mongoose, Herpestes auropunctatus.

The male mongoose, Herpestes auropunctatus, displays a distinct seasonal reproductive rhythm in environments which show minimal changes in daylength. This investigation was designed to evaluate whether the reproductive system of the male mongoose was responsive to photoperiodic manipulations. Four experiments were conducted; two during the breeding season, one during the inactive season, and one during the recrudescence phase. Serum androgen levels and reproductive organ weights were similar in males exposed to either short (6L:18D) or control photoperiods (14L:10D) when the photoperiodic adjustment was initiated in April; however, serum androgen levels were significantly depressed after 60 days exposure to short photoperiods as were weights of prostate glands when the photoperiodic manipulation was initiated in May. An increase in the number of hours of light per day during the inactive season did not affect serum androgen levels or reproductive organ weights. Exposure to a very short photoperiod (2L:22D) during the recrudescence phase delayed, but did not prevent, the increase in serum androgen levels. Although the reproductive system of the male mongoose is responsive to daylength adjustments, the response is less pronounced when compared to the effects of photoperiod in other seasonal breeders.

Androgens↗

Presence of two neuropeptides in the fusiform ganglion and reproductive ducts of Octopus vulgaris: FMRFamide and gonadotropin-releasing hormone (GnRH).

We have found evidence of FMRFamide-like and cGnRH-I-like immunoreactivity in the central nervous system (CNS) and in the reproductive ducts of both female and male cephalopod Octopus vulgaris. Cell bodies and fibers were immunolocalized in the fusiform ganglion from which the nerves that reach the female and male reproductive ducts arise. FMRFamide-like and cGnRH-I-like immunoreactive nerve endings were present in the oviduct, and in the oviducal gland of the female and in the seminal vesicle of the male. The GnRH-like peptide from the reproductive ducts has been partially characterized by HPLC. The retention time of the Octopus vulgaris GnRH-like peptide was similar to the retention time of cGnRH-I. Based on these observations we suggest that FMRFamide-like and a novel GnRH-like peptide are involved in the control of reproductive ducts of Octopus vulgaris. One possibility is that the peptides affect gamete transport. Another possibility is that they regulate secretory products such as mucus and mucilaginous substances from the oviducal gland and the seminal vesicle. Our data provide further evidence to support the hypothesis of the existence of a central and peripheral peptidergic control of reproduction of Octopus vulgaris.

Animals↗

Nuchal translucency in dichorionic twins conceived after assisted reproduction.

OBJECTIVES: As opposed to biochemical markers of Down syndrome, nuchal translucency (NT) was once thought to be a more reliable screening marker for high order multiple pregnancies and pregnancies conceived after assisted conception. Recent data suggested that NT in singleton fetuses from assisted reproduction technology (ART) was thicker than those from singleton pregnancies. The present study compared the thickness of NT in dichorionic twins from natural conception and assisted reproduction. METHODS: A retrospective analysis for comparison of NT thickness on 3319 spontaneous singletons, 19 pairs of spontaneous twins and 27 pairs of assisted reproduction twins was performed. RESULTS: The median NT multiple of median (MoM) of spontaneous singletons was 1.00. For twins, the median NT MoM for pregnancies after assisted reproduction and natural conception were 1.02 and 1.07 respectively. There was no statistical difference in the NT thickness among the three pregnancy groups. CONCLUSION: Contrary to the observed increase in NT in singleton pregnancies from assisted reproduction, the NT in dichorionic twins was comparable to the spontaneous ones. The mode of conception appears to impose differential influence on singletons and twins.

Female↗

Iteroparous reproduction strategies and population dynamics.

Asymptotic relationships between a class of continuous partial differential equation population models and a class of discrete matrix equations are derived for iteroparous populations. First, the governing equations are presented for the dynamics of an individual with juvenile and adult life stages. The organisms reproduce after maturation, as determined by the juvenile period, and at specific equidistant ages, which are determined by the iteroparous reproductive period. A discrete population matrix model is constructed that utilizes the reproductive information and a density-dependent mortality function. Mortality in the period between two reproductive events is assumed to be a continuous process where the death rate for the adults is a function of the number of adults and environmental conditions. The asymptotic dynamic behaviour of the discrete population model is related to the steady-state solution of the continuous-time formulation. Conclusions include that there can be a lack of convergence to the steady-state age distribution in discrete event reproduction models. The iteroparous vital ratio (the ratio between the maximal age and the reproductive period) is fundamental to determining this convergence. When the vital ratio is rational, an equivalent discrete-time model for the population can be derived whose asymptotic dynamics are periodic and when there are a finite number of founder cohorts, the number of cohorts remains finite. When the ratio is an irrational number, effectively there is convergence to the steady-state age distribution. With a finite number of founder cohorts, the number of cohorts becomes countably infinite. The matrix model is useful to clarify numerical results for population models with continuous densities as well as delta measure age distribution. The applicability in ecotoxicology of the population matrix model formulation for iteroparous populations is discussed.

Animals↗

N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats.

Estrogen interacts with N-methyl-d-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In the hippocampus, estrogens increase both dendritic spine density and synapse number, and NMDA antagonists block these effects. This plasticity in the hippocampus mediated by estrogen may be of particular importance in the context of aging when estrogen levels change and cognitive function is often impaired. Therefore, the present study was designed to investigate effects of aging and reproductive status on NMDA receptor (NR) subunit mRNA levels in the hippocampus. NR1, NR2A, and NR2B mRNA levels were measured by RNase protection assay in young (3-4 month), middle-aged (12-13 month), and aged (24-25 month) Sprague-Dawley rats in different phases of the estrous cycle in cycling animals and in acyclic subjects. Our results demonstrated that NMDA receptor subunit mRNA levels were much more prominently affected by the chronological age than by the reproductive status of the animals. Age-related changes were observed in NR1, NR2A, and NR2B in the ventral hippocampus and in NR1 and NR2B in the dorsal hippocampus. However, the only relationship with reproductive status was seen for NR1 mRNA, and this was restricted to the ventral hippocampus. An interaction between chronological age and reproductive status was found, with higher levels of NR1 mRNA seen in young animals in proestrus than in those in diestrus I (high and low estrogen levels, respectively). However, this relationship was not seen in the aged subjects. These results demonstrate that the hippocampus is subjected to age-related alterations in NMDA receptor subunit mRNA levels and that animals of different ages are influenced differently by reproductive status. This shift in the NMDA receptor mRNA levels may be a possible molecular mechanism contributing to alterations in cognitive behavior during normal aging.

Aging↗

Assessment of the reproductive and developmental toxicity of pesticide/fertilizer mixtures based on confirmed pesticide contamination in California and Iowa groundwater.

Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100 x the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-1 mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1x, 10x, and 100x) where 1x was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F0 or F1 mice at doses up to 100x the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F0 or the F1 generation mice exposed to either CAL or IOWA at up to 100x. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats).

Animals↗

Reproductive and developmental toxicity studies of silicone gel Q7-2159A in rats and rabbits.

Studies reported here assessed the potential adverse effects of silicone gel, Dow Corning Q7-2159A, on general reproduction and fetal development in male and female Charles River CD rats and New Zealand white rabbits. Two control and three treatment groups of 30 male and 30 female rats and 25 female rabbits per group were used in the one-generation reproduction and developmental toxicity studies, respectively. The silicone gel was implanted subcutaneously in two flank sites at dosage levels of 3, 10, and 30 ml/kg. The highest dose was selected on the basis of likely human body burden. Control groups received either sterile saline or carboxymethylcellulose solution in two flank implantation sites. The control and test articles were implanted in male and female rats 61 and 47 days, respectively, prior to mating (in the rat reproduction study) and approximately 42 days prior to insemination of female rabbits (in the rabbit developmental toxicity study). There were no treatment-related effects on F0 parental general conditions and reproductive performance, F1 neonatal viability, or growth in the rat reproduction study. No maternal nor developmental effects, including teratogenicity, were observed in rabbits in the groups implanted with Q7-2159A gel in the developmental toxicity study.

Abnormalities, Drug-Induced↗

Reproductive and developmental toxicity studies of silicone elastomer Q7-2423/Q7-2551 in rats and rabbits.

The purpose of these studies was to assess the potential adverse effects of silicone breast implant envelope elastomer on general reproduction and fetal development in rats and rabbits. One control and one treatment group of 30 male and 30 female Charles River CD rats and 25 inseminated New Zealand white rabbits per group were used in the one-generation reproductive and developmental toxicity studies, respectively. Two 1.2-cm discs of silicone elastomer were subcutaneously implanted in one site in the left flank and one site in the right-flank of the treated group of rats, while four 2.5-cm discs were implanted in two sites in the left flank and two sites in the right flank of the treated group of rabbits. The size of the elastomer implants was chosen to approximate the expected body burden of women with breast implants. The control animals in both studies received subcutaneous implantation of either 1.2- or 2.5-cm discs of polyethylene of the same number in the same locations. The control and test articles were implanted in the male and female rats at 61 and 47 days, respectively, prior to mating (in the rat reproduction study) and approximately 42 days prior to insemination of female rabbits (in the rabbit developmental toxicity study). Subcutaneously implanted discs of silicone breast implant envelope elastomer did not induce maternal or developmental toxicity before or during pregnancy or during lactation, did not cause any adverse effects on the parents or neonates, and did not impair reproductive performance in the rat reproduction study. No maternal toxicity or adverse developmental effects, including teratogenicity, were observed in the treated groups in the rabbit developmental toxicity study.

Abnormalities, Drug-Induced↗

Nonclinical toxicology studies with zidovudine: reproductive toxicity studies in rats and rabbits.

Zidovudine (ZDV) was evaluated for adverse effects on reproduction and fetal development in animal test species. Standard preclinical tests for reproduction and fertility, developmental toxicity, and postnatal toxicity were conducted in CD (Sprague-Dawley) rats and a developmental toxicity study was conducted in New Zealand white rabbits. In an additional study, reproductive outcome was characterized in female rats given ZDV before, during, or after mating and drug levels in the plasma and milk of lactating rats were determined. Finally, drug exposure data including observed peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC) were evaluated for pregnant rats and rabbits. In a reproduction/fertility study in CD rats, toxicity to the early rat embryo, manifested as an increase in early resorptions and a decrease in litter size, was noted following dosage of the parental animals with 75 or 225 mg ZDV/kg bid. A dose of 25 mg/kg bid was a no-effect level in rats. At the time of mating, male rats had been dosed for 85 days, and females had been dosed for 26 days. To further evaluate the effects of ZDV on reproduction, dosing of male rats was continued to 149 days when they were mated a second time to virgin, untreated females. All reproductive parameters were normal in the untreated females from this second mating, indicating that the embryotoxic effect of the drug was not likely mediated by a genotoxic or other effect in the male. A separate study in female CD rats given 225 mg/kg bid for various periods pre- or postconception suggests that the toxic effect of ZDV is primarily to the early rodent embryo. Early embryo death did not occur in rats or rabbits in standard developmental (teratology) studies; however, pregnant New Zealand white rabbits given 250 mg/kg bid during gestation Days 6-18 showed reduced weight gain, anemia, and an increase in late fetal deaths. No other evidence of developmental toxicity was noted in either species, and ZDV was not teratogenic in rats or rabbits given up to 250 mg/kg bid during the period of major organogenesis. At this dose, Cmax values in rats and rabbits were approximately 234 and 150 times higher, respectively, than the mean steady-state serum concentration in adults following chronic oral administration of 250 mg every 4 hr. In both the reproduction/fertility study and a peri- and postnatal study in rats, liveborn offspring showed no adverse effects on survival, growth, or developmental measurements.

Animals↗

Two-generation reproductive toxicity study of dietary tributyl phosphate in CD rats.

Tributyl phosphate (TBP) was tested for reproductive toxicity in rats. Thirty weanlings/sex (F0) were exposed to TBP in the diet ad libitum at 0, 200, 700, or 3000 ppm for 10 weeks and then randomly mated within groups for 3 weeks with continued exposure. F0 parents and 10 F1 weanlings/sex/dose were necropsied, and adult reproductive organs, urinary bladders (both sexes), kidneys (males), and livers (females) were evaluated histologically. Thirty F1 weanlings/sex/dose continued exposure for 11 weeks and were bred as described above. F1 parents and F2 weanlings, 10/sex/dose, were then necropsied as described above. Adult toxicity was observed in both sexes and generations at 700 and 3000 ppm; observations included reduced body weights, weight gain and feed consumption, urinary bladder epithelial hyperplasia (both sexes), renal pelvis epithelial hyperplasia only at 3000 ppm (male kidneys), and centrilobular hypertrophy (female livers). At 200 ppm, transient reductions in body weight were observed in F0 and F1 females, with urinary bladder epithelial hyperplasia in F0 males and females and in F1 males. There was no evidence of reproductive toxicity, of reproductive organ pathology, or of effects on gestation or lactation at any dose tested. Postnatal toxicity was evidenced by consistent reductions in F1 and F2 pup body weights at 3000 ppm and by occasional weight reductions in F2 litters at 700 ppm, and was associated with maternal toxicity observed at these doses and times. Under the conditions of this study, a NOAEL was not determined for adult toxicity; the NOAEL for reproductive toxicity was at least 3000 ppm and the NOAEL for postnatal toxicity was approximately 200 ppm.

Animals↗

Plasma insulin-like growth factor-I concentration during the reproductive cycle of the American alligator (Alligator mississippiensis).

Insulin-like growth factor I (IGF-I) is involved in the growth, reproduction, and development of vertebrates. In this study, we report plasma IGF-I concentrations throughout the reproductive cycle of the American alligator (Alligator mississippiensis) and consider these concentrations with respect to several reproductive steroid hormones and ions involved in reptilian reproduction. Mean plasma IGF-I concentrations were significantly different among reproductive stages. Maximal plasma concentrations of IGF-I were observed throughout gravidity. Plasma IGF-I concentration was not correlated with plasma concentrations of estradiol-17 beta, calcium, phosphorus, albumin, total protein, or body size, but was correlated with plasma progesterone concentration. We hypothesize that the elevated concentrations of IGF-I in gravid female alligators are due to the synthesis of this hormone for incorporation into eggs as well as residual IGF-I that could function in the stimulation of uterine secretory products.

Alligators and Crocodiles↗

The reproductive cycle of the female American alligator (Alligator mississippiensis).

We examined ovarian and oviducal gross morphology and collected blood samples from wild female alligators in central Florida during most of the year. Females with vitellogenic follicles were observed throughout the year, although ovaries containing follicles larger than 15 mm were seen only during the spring and early summer (March-June). We detected a poor relationship between female body size and the number of vitellogenic follicles whereas body size was significantly correlated with clutch size. Plasma samples were analyzed for (1) estradiol-17beta (E2), testosterone (T), and corticosterone by specific radioimmunoassays; (2) vitellogenin by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis; and (3) total protein, phosphorus, and calcium by spectrophotometric assays. Reproductively active females showed elevated plasma concentrations of E2 during the fall (September-November) and spring (March-May) whereas non-reproductively active females exhibited basal levels with no apparent peaks. Vitellogenin was detected in the plasma during the same months that plasma E2 concentrations were elevated. Elevated plasma vitellogenin and E2 were not correlated with plasma total protein but were correlated with plasma calcium concentration. During late vitellogenesis, plasma T concentrations were elevated in reproductively active females coincident with a period of intense courtship and mating. Corticosterone plasma concentrations exhibit no significant monthly variation, nor apparent changes during various stages of reproductive activity although plasma concentrations were elevated during late gravidity. Our data suggest that female reproductive activity begins in the fall with an increase in plasma E2 concentration in September or October and vitellogenesis in October. Ovarian activity slows during winter and reactivates with the onset of spring.

Alligators and Crocodiles↗

The effects of an "El Niño" southern oscillation event on reproduction in male and female blue-footed boobies, Sula nebouxii.

This study attempted to determine endocrine correlates of reproductive success in relation to major deleterious environmental conditions. In 1992, an El Niño southern oscillation event resulted in complete reproductive failure in a colony of blue-footed boobies, Sula nebouxi, on Isla Isabel in the Pacific Ocean off San Blas, Nayarit, Mexico (21.5 degrees N, 105.5 degrees W). In 1993, the El Niño event had waned and reproductive success was high. The mean sea surface temperature in 1992 was 26.69 degrees, the warmest year for 11 years of data (mean, 25.63 degrees ). In 1993, mean sea surface temperature was 25.75 degrees. Plasma levels of testosterone were highest during the egg-laying period in 1993 and declined markedly during incubation. There were no differences between males and females. Comparisons of testosterone levels between 1992 and 1993 (egg-laying time point removed for 1993) showed no significant differences. Thus reproductive failure during an El Niño year was not related to testosterone levels. Baseline plasma levels of corticosterone did not change over the nesting cycle in either sex. There was a trend for plasma levels of corticosterone to be higher in males and females during the earlier stages of breeding in 1992 compared with 1993, and if all levels were combined within years then females showed significantly higher plasma levels of corticosterone in the El Niño year. Plasma levels of corticosterone showed marked increases following capture and handling in both sexes and at every stage of the breeding cycle in each year. There was no variation in the adrenocortical responses to stress with year or stage of nesting in males. However, in females, maximum corticosterone levels were greatest during the parental phase of 1992, the El Niño year, when all nests ultimately failed. Comparisons of the dynamics of corticosterone changes during the capture stress protocol revealed no correlations with body mass in 1992 or 1993. These data suggest that although massive reproductive failure in the El Niño year was not related to testosterone levels, baseline circulating concentrations of corticosterone may have a role in inhibiting onset of breeding. In contrast, after the nesting cycle has been initiated, increased adrenocortical sensitivity to acute stress may be involved in nest abandonment.

Adrenal Cortex↗

Seasonal growth of song control nuclei precedes seasonal reproductive development in wild adult song sparrows.

In seasonally breeding adult songbirds, the brain regions that control song undergo dramatic seasonal morphological changes. During late winter and early spring, increasing day length triggers an increase in circulating testosterone that ultimately causes several song nuclei to grow in volume. The timing of this growth relative to the seasonal development of the reproductive system is not known. This question was investigated in two populations of wild song sparrows (Melospiza melodia morphna). Both populations live at the same latitude (46 degrees N), but breed at different altitudes. One population resides on the Pacific coast in Washington, and the other resides in the foothills of the Cascade Mountains. Both populations experienced the same photoperiodic conditions, but the timing of seasonal reproductive development differed between populations. Coastal birds initiated gonadal recrudescence approximately 2 weeks earlier than montane birds. Despite this temporal difference in reproductive development, there were no differences between these groups in the seasonal growth of two song control nuclei, HVc and RA. During late February, both groups had low circulatory levels of testosterone (mean for coastal birds was 1.01 +/- 0.37 ng/ml; mean for montane birds was 1.41 +/- 0.26 ng/ml) and fully recrudesced song nuclei (for example, mean HVc volume in coastal birds was 1.77 +/- 0.08 mm(3); mean HVc volume in montane birds was 1.76 +/- 0.09). Also at this time, both populations were in the earliest stages of seasonal reproductive development as judged by the degree of gonadal recrudescence (mean gonad volume was less than 10% of typical breeding size in both populations). It is concluded that seasonal song system growth is completed before seasonal reproductive development in response to submaximal levels of circulating testosterone.

Animals↗

90-day feeding and one-generation reproduction study in Crl:CD BR rats with 17 beta-estradiol.

Over the past several years, there has been increasing concern that chemicals and pesticides found in the environment may mimic endogenous estrogens, potentially producing adverse effects in wildlife and human populations. Because estrogenicity is one of the primary concerns, a 90-day/one-generation reproduction study with 17 beta-estradiol was designed to set dose levels for future multigenerational reproduction and combined chronic toxicity/oncogenicity studies. The purpose of these studies is to evaluate the significance of a range of responses as well as to provide benchmark data for a risk assessment for chemicals with estrogen-like activities. This 90-day/one-generation reproduction study was conducted in male and female Crl:CD BR rats using dietary concentrations of 0, 0.05, 2.5, 10, and 50 ppm 17 beta-estradiol. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In addition, several mechanistic/biochemical endpoints were evaluated for their usefulness in follow-up studies. In the P1 generation, dietary administration of 2.5, 10, and 50 ppm 17 beta-estradiol produced dose-dependent decreases in body weight, body weight gain, food consumption, and food efficiency. At 10 and 50 ppm 17 beta-estradiol, minimal to mild nonregenerative anemia, lymphopenia, decreased serum cholesterol (50 ppm only), and altered splenic lymphocyte subtypes were also observed in the P1 generation. Additionally, at these concentrations, there were changes in the weights of several organs. Evidence of ovarian malfunction, characterized by reduced numbers of corpora lutea and large antral follicles, was observed at 2.5 ppm 17 beta-estradiol and above. Other pathologic changes in males and females fed 10 and 50 ppm 17 beta-estradiol included centrilobular hepatocellular hypertrophy; diffuse hyperplasia of the pituitary gland; feminization of the male mammary glands; mammary gland hyperplasia in females; increased number of cystic follicles in the ovary; hypertrophy of the endometrium and endometrial glands in the uterus; degeneration of seminiferous epithelium; and atrophy of the testes and the accessory sex glands. In the reproduction portion of this study, rats fed 10 or 50 ppm 17 beta-estradiol did not produce litters. While there was no evidence that the 50 ppm treated rats mated, 33.3% of the rats fed 10 ppm mated but did not produce litters. No effects on mating and fertility indices were observed in rats fed 0.05 and 2.5 ppm 17 beta-estradiol. Pup weights at birth were statistically decreased relative to control in the groups fed 0.05 and 2.5 ppm 17 beta-estradiol. Weights of the rats in the 0.05 ppm group recovered by postnatal day 4 and remained similar to control throughout the remainder of the study. The mean gestation length of the 0.05 ppm group was slightly, albeit not statistically significantly, shorter (0.5 days) than that of the control group, which may have contributed to the decrease in birth weight of the 0.05 ppm group. In contrast, the weights of the F1 generation rats fed 2.5 ppm 17 beta-estradiol remained decreased relative to the control group throughout the study. Parental administration of 17 beta-estradiol did not alter anogenital distance in male or female pups. The onset of sexual maturation, as measured by day of preputial separation in males and day of vaginal opening in females, was delayed in male rats fed 2.5 ppm (by 8.2 days) and was hastened in female rats fed 0.05 and 2.5 ppm (by 1.6 and 8.8 days, respectively). The age at vaginal opening ranged from 26 to 37, 26 to 35, and 21 to 25 days for rats fed 0, 0.05, and 2.5 ppm 17 beta-estradiol, respectively. Hence, the range of age at vaginal opening was similar between the control and 0.05 ppm group. The organ weight and pathologic alterations observed in the adult F1 generation rats were similar to those observed in the P1 generation rats. (ABSTRACT TRUNCATED)

Animals↗

Discrete event versus continuous approach to reproduction in structured population dynamics.

The governing equations are derived for the dynamics of a population consisting of organisms which reproduce by laying one egg at the time, on the basis of a simple physiological model for the uptake and use of energy. Two life stages are assumed, the egg and the adult stage where the adults do not grow. These assumptions hold true, for instance, for rotifers. From the model for the life history of the individuals, a physiologically structured population model for a rotifer population is derived. On the basis of this discrete event reproduction population model a continuous reproduction population model is proposed. The population model together with the equation for the food result in chemostat equations which are solved numerically. We show that for the calculation of the transient population dynamic behaviour after a step-wise change of the dilution rate, an age structure suffices, despite the size and energy structure used to describe the dynamics of the individuals. Aggregation of the continuous reproduction population model yields an approximate lumped parameter model in terms of delay differential equations. In order to assess the performance of the models, experimental data from the literature are fitted. The main purpose of this paper is to discuss the consequences of discrete event versus continuous reproduction. In both population models death by starvation is taken into account. Unlike the continuous reproduction model, the discrete model captures the experimentally observed lack of egg production shortly after the step change in the dilution rate of the chemostat.

Age Factors↗

Hypothalamic-pituitary-ovarian interactions during reproductive senescence in the rat.

The neuroendocrine status of Long-Evans female rats was evaluated at several key stages of reproductive senescence. Young (4-8 mo), middle-aged (10-14 mo) and old (24-30 mo) animals were studied according to reproductive state. The reproductive states studied were (1) regularly cycling, (2) constant estrus and (3) pseudopregnant, as determined by vaginal smear cytology. Neuroendocrine parameters at the levels of the hypothalamus, pituitary and steroid-producing organs were compared between each group. DA3, E and NE concentrations in the median eminence of the hypothalamus were determined by a highly sensitive radioenzymatic assay. LRF content in the median eminence was measured by radioimmunoassay. Circulating levels of LH, FSH, PRL and six steroids were determined. Changes in hormone and neurotransmitter concentrations were deomonstrated in association with the various stages of reproductive senescence and with age advancement. These changes involved the hypothalamic, pitiutary and steroid systems. NE content in the median eminence, FSH in serum and circulating androstenedione were all significantly increased in middle-aged, cyclic rats prior to the onset of senescent anovulation. DA concentration in 24 mo. old constant estrous rats (30.7 +/- 7.7 pg/microgram, N = 6) and in 30 mo. old pseudopregnant rats (27.5 +/- 7.1 pg/microgram, N = 6) was significantly reduced compared to young (6 mo. old), cyclic controls on proestrous (55.0 +/- 4.7 pg/microgram, N = 12). This DA reduction was associated with a 3-fold increase in circulating prolactin. The results are discussed in terms of a regulatory cascade model of female reproductive senescence (Finch, 1976).

Aging↗

Assessment of chemicals affecting the male reproductive system.

The reproductive toxicologist must be more concerned with the ability of laboratory models to predict human reproductive hazards and to estimate human health risks. Although more than a hundred chemicals have been reported to affect the reproductive capacity of male laboratory animals, fewer than 15 environmental chemicals have been shown conclusively to affect man and many of these are known mutagens, carcinogens or otherwise generally toxic agents. Pharmacokinetic and adaptive factors must be considered. More attention also needs to be directed towards processes other than spermatogenesis and towards mechanisms of toxicity other than cytotoxicity. The male component necessary for successful reproduction depends on a large variety of biological processes working in concert. The ability to assess chemically-induced reproductive effects needs to be refined and modern molecular and cellular approaches should be developed and validated. This paper summarizes aspects of the pharmacokinetic and adaptive factors involved in testicular toxicity, some current laboratory assessment techniques, and newer test procedures such as monoclonal antibodies for sperm surface proteins and the interspecies (human/hamster) sperm penetration assay.

Animals↗