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Serum concentrations of steroid hormones during reproduction in the Atlantic stingray, Dasyatis sabina.

The Atlantic stingray, Dasyatis sabina, has a well-defined annual reproductive cycle in Florida. We collected adult specimens over 12 months and evaluated reproductive parameters and serum levels of five steroid hormones, 17beta-estradiol (E2), progesterone (P4), testosterone (T), dihydrotestosterone (DHT), and corticosterone (CS). Female E2 peaked twice, once in mid-March to early April in association with ovulation and again in mid-June to mid-July in association with the enlargement of a second group of ovarian follicles. Female P4 peaked in early March and early April, coincident with the peak in E2. Female DHT was variable but exhibited a pattern not clearly associated with known events in the reproductive cycle. Female T and CS levels did not vary significantly through time. In males, T, DHT, and CS increased progressively through winter and spring, peaking in March when females were ovulating and when copulation probably took place. DHT concentrations were usually at least twice T levels. These three hormones peaked long after the November/December peak in gonadosomatic index. E2 was measurable in males and was highest during the period of testicular development. Male P4 varied in a pattern not clearly associated with known reproductive events.

Animals↗

Two-generation reproduction study of ammonium perchlorate in drinking water in rats evaluates thyroid toxicity.

Perchlorate is an inorganic ion that has recently been detected in drinking water supplies throughout the country, but little is known about its effects on reproductive function. This two-generation reproductive study examines the effects of ammonium perchlorate on the male and female reproductive systems in rats, and on the growth and development of offspring. Adult Sprague-Dawley rats (30/sex/group) were given continuous access to ammonium perchlorate in their drinking water at doses of 0, 0.3, 3.0, and 30.0 mg/kg-day. F1 generation rats were given the same ammonium perchlorate doses as their respective P1 generation sires and dams beginning at weaning and continuing through the day of sacrifice. Standard reproductive parameters were evaluated; blood was collected for determination of serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels. Histopathological examination was conducted on major tissues, including the thyroid. No significant changes in developmental parameters were observed. In the F1 generation adult rats, relative thyroid weights were significantly increased in all dose groups for female rats and in the 3.0 and 30.0 mg/kg-day dose groups for male rats. Histopathologic changes in the thyroid consisted of hypertrophy and hyperplasia that increased in incidence and severity in a dose-related manner. Dose-related, statistically significant changes in TSH and T4 or T3 occurred at doses higher than those that resulted in changes in thyroid weight and thyroid histopathology, 30 mg/kg-day. Thus, perchlorate is not a reproductive toxicant in rats when administered in the drinking water at doses up to 30 mg/kg-day, but it can affect the thyroid at doses > or =3 mg/kg-day. Based on these findings, 0.3 mg/kg-day is identified to be the no-observable-adverse-effect level (NOAEL) for this study.

Animals↗

The effects of cannabinoids on the regulation of reproduction.

It has been shown that the main psychoactive component of marihuana, delta9-tetrahydrocannabinol (THC) has mainly inhibitory effects on the regulation of reproduction. Recently, the purification and availability of the endogenous ligand of the cannabinoid receptor, arachidonyl ethanolamide, anandamide, (ANA) and its specific long lasting antagonist, the SR 141716 (SR) provided us the opportunity to compare the effects of THC and ANA on the neuroendocrine regulation of reproduction. ANA decreases serum luteinizing hormone (LH) and prolactin (PRL) levels in rats of both sexes. It has no action on serum follicle stimulating hormone (FSH) level. When ANA was administered to pregnant rats it resulted in an increase of the duration of pregnancy and in the frequency of stillbirths. The postnatal development of hypothalamo-pituitary axis in offspring was temporarily inhibited. In conclusion, we found that exogenous and endogenous cannabinoids have only slightly different effects on the reproductive parameters. These effects may occur via the central cannabinoid receptor. It is possible that the sites of action are at both hypothalamic and pituitary levels. The results further support the view that ANA may be a central neurotransmitter or neuromodulator.

Animals↗

Central effects of photoperiod on reproduction in the ram revealed by the use of a testosterone clamp.

Over a 3-year period eight adult Soay rams were exposed to an artificial lighting regimen of alternating 16-week periods of long days (16 h light: 8 h darkness; 16L : 8D) and short days (8L : 16D) to induce a seasonal cycle in reproduction and wool growth every 32 weeks. Early in the study the rams were castrated (four during long days and four during short days) and 48 weeks later the castrated animals were each given an s.c. implant of testosterone to increase the blood plasma concentration of testosterone to 14-20 nmol/l. The changes in the concentrations of LH, FSH and testosterone were measured in blood samples collected once or twice weekly while records were made of the changes in the size of the testes (before castration), the intensity of the sexual skin flush, the expression of aggressive and sexual behaviour and the rate of wool growth. The results showed that in the castrated rams there were only minor changes in the blood levels of LH, FSH and the expression of aggressive behaviour related to the 32-week light cycle, while the sexual skin flush was permanently absent. However, after the commencement of the constant testosterone therapy, there were major changes in all the reproductive parameters related to the lighting regimen with a similar temporal relationship as observed in the rams before castration. Cyclic variation in wool growth occurred throughout the study related to the changes in photoperiod but this was not markedly affected by castration and testosterone replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

Cadmium chronic administration to lactating ewes: reproductive performance, cadmium tissue accumulation and placental transfer.

20 lactating ewes were allotted to two groups: 10 subjects received orally 100 mg/day of CdCl2 for 108 consecutive days, and the remaining 10 acted as control. Reproductive performance in ewes and cadmium tissue accumulation, both in ewes and their lambs, were investigated. The results showed that in ewes: 1) the regular cadmium intestinal intake negatively influences all reproductive parameters; 2) cadmium is particularly accumulated in kidney and liver, but also in mammary gland, although at a distinctly lower level; 3) chronic administration does not increase cadmium placental transfer in lactating pregnant subjects.

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↗

Breeding performance of great tits (Parus major) along a gradient of heavy metal pollution.

The possible effects of heavy metal pollution on various breeding parameters of the great tit (Parus major) were studied at four study sites in a pollution gradient near a large nonferrous smelter in Belgium during three consecutive breeding seasons. Significantly more females interrupted their laying period near the pollution source than did females farther away. At the two most polluted sites, hatching success was significantly reduced compared to two lesser-polluted study sites. Overall breeding success was also significantly lower toward the factory complex. This lowered breeding success was caused not only by the decreased hatching success toward the pollution source but also by the significant difference in fledging success among sites. Although a clear relationship was observed between the exposure to heavy metal pollution and an impaired reproduction, not all reproductive parameters were affected. We found no significant differences in the onset of laying, clutch size, length of the incubation period, and the proportion of nests with low-quality eggs among sites. Although nest box occupancy was every year slightly lower toward the smelter compared to farther away, differences among study sites were never significant.

Animals↗

[Genetic and epidemiological studies in Dagestan highland isolates].

Interpopulation differences in the epidemiology and age of onset of complex diseases, as well as expression of some vital parameters, have been found. The relationship between these interpopulation differences and the genetic processes that have been occurring in the populations throughout their history has been demonstrated. The Daghestan genetic isolates studied are characterized by aggregation of certain complex diseases. In each genetic isolate, almost all affected subjects with homogeneous clinical phenotypes belong to the same large pedigree with a limited number of founders. There is evidence for a large variance of the population risk of schizophrenia (morbid risk) in Daghestan isolates (this parameter varies from 0 to 5%). Examination of 211 cases of schizophrenia earlier diagnosed in Daghestan psychiatric hospitals has shown that only 139 of them meet the DSM-IV criteria for schizophrenia. The remaining 72 subjects have, according to DSM-IV criteria, various schizoaffective and affective disorders; all of these subjects are close relatives of the schizophrenic patients. The age of onset of schizophrenia in the isolates studied varies from 14 to 40 years (20.84 +/- 0.568 years). Offspring of consanguineous marriages exhibit later age at onset and a higher risk of schizophrenia than offspring of exogamous marriages. The results of multivariate genetic analysis indicate that different gene complexes are involved in the pathogeneses of early-onset and late-onset forms of schizophrenia. An association of schizophrenia incidence, its age dependence, and reproductive parameters with polymorphisms of some microsatellite loci have been demonstrated.

Adolescent↗

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↗

Early lactation responses of Holstein cows fed a rumen-inert fat prepartum, postpartum, or both.

Primiparous (n = 22) and multiparous (n = 41) cows were randomly assigned by calving date and parity to one of four dietary sequences of supplemental fat from 14 d prepartum to 151 d postpartum. Partially hydrogenated tallow was added to diets at 0% prepartum and postpartum (control); 1% prepartum and 2% postpartum; 0% prepartum and 2% postpartum; and 0% prepartum, 0% from 1 to 34 d postpartum, and 2% from 35 to 151 d postpartum. Inclusion of partially hydrogenated tallow did not influence yields of milk or 3.5% FCM, milk composition, or DMI during the first 151 d postpartum. During the first 35 d postpartum, cows receiving partially hydrogenated tallow starting at parturition yielded milk with a higher fat content than those receiving fat prepartum and postpartum. Addition of partially hydrogenated tallow to diets starting 35 d postpartum resulted in cows being more persistent in yields of milk and 3.5% FCM from 60 to 151 d postpartum. Reproduction parameters measured were unaffected by time of fat addition to diets. Our data suggest that delaying the addition of partially hydrogenated tallow to diets until 35 d postpartum may improve the persistency of lactation.

Animals↗

Maternal exposure to diphenhydramine during the fetal period in rats: effects on physical and neurobehavioral development and on neurochemical parameters.

Previous research from our laboratory suggested that the administration of antihistaminics (H(1) receptor antagonists) to pregnant Wistar rats throughout pregnancy altered brain sexual differentiation and dopaminergic physiology of the offspring. In the present study, we assessed the effects of 20 mg/kg diphenhydramine (DPH) administration to pregnant rats during the fetal period of pregnancy [Gestation Days (GDs) 16-21], a critical period for brain sexual differentiation and central nervous system (CNS) maturation. Maternal body weight and water and food consumption were measured during pregnancy and offspring physical and behavioral development were evaluated during lactation. Offspring open-field behavior was assessed at 21 and 100 days of age. After the final open-field test, male and female sexual behavior, stereotypy following an apomorphine challenge, striatal content of dopamine (DA), the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), serotonin (5-HT) and the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were assessed. There were no significant treatment-related changes in maternal reproductive parameters, but DPH treatment decreased maternal body weight gain during the treatment period. Offspring physical parameters were not altered in the treated group, and no significant treatment-related changes were found in female open-field measures, sexual behavior or in striatal neurochemical measurements. However, delayed testis descent and altered patterns of sexual behavior occurred in male offspring accompanied by increased striatal DA, decreased striatal DOPAC as well as reduced DOPAC/DA, HVA/DA and 5-HIAA/5-HT ratios. Taken together, these data suggest that exposure to DPH during the fetal period of rat development altered postnatal CNS maturation and sexual development of male offspring via changes in striatal bioamine systems.

Age Factors↗

Multigenerational exposure to phytosterols in the mouse.

Due to beneficial health effects phytosterols (PS) are increasingly added to functional foods. The aim of the present study was to investigate the chronic effects of a dietary PS mixture (5mg/kg/day), containing mainly beta-sitosterol, on the reproduction of the mouse. General reproductive parameters, postnatal development, growth and survival of pups, weight of sex organs, the concentrations of plasma sex steroids and testicular testosterone were monitored across five generations (F(0)-F(4)). PS exposure increased the plasma levels of testosterone and decreased the relative uterine weights in the pups of F(2) and F(4) generations. Furthermore, PS exposure increased the concentrations of plasma estradiol in the female pups of F(3) generation. PS supplement also increased the testicular levels of testosterone in the male pups of F(2) generation. In spite of these transitory changes, PS exposure caused no permanent deleterious effects on the reproduction of the mouse.

Administration, Oral↗

Evaluation of spinosad in a two-generation dietary reproduction study using Sprague-Dawley rats.

Spinosad, an insecticide derived from a naturally occurring bacterium via fermentation, represents a new class of insecticides acting by a novel mode of action. A dietary study was conducted in Sprague-Dawley rats in which groups of 30 rats/sex/dosage level were given diets that provided 0, 3, 10, or 100 mg spinosad/kg body weight/day, 7 days/week, for 2 successive generations. Following 10 weeks of dietary exposure, the P1 generation was mated twice to produce F1a and F1b litters. After weaning, groups of 30 rats/sex/dosage level were selected from the F1a litters, given diets containing spinosad for 12 weeks, and mated to produce the F2 generation. Dietary administration of spinosad to rats at a dosage of 100 mg/kg/day over 2 generations produced parental toxicity and effects on the offspring. Among adult males, body weights and weight gains were decreased 2-9% relative to controls, with P1 males more affected than P2. Absolute and relative liver, kidney, heart, spleen, and thyroid weights were increased by from 12% to as much as 240% of control values. Histologic changes consistent with cationic amphiphilic compounds were noted in the kidneys, lungs, mesenteric lymph nodes, spleen, and thyroid of P1 and P2 males and females. In females given 100 mg/kg/day, though premating body weights were not affected, weight gains during the F1a and F1b gestation periods were depressed 15-16%. Increased incidences of dystocia, and vaginal bleeding and mortality occurred during parturition and lactation at 100 mg/kg/day. Effects on the offspring (decreased litter size and survival through day 4 of lactation) were limited to the high-dosage group. Signs indicative of poor maternal care noted in the pups (stomachs void of milk, cold, thin, etc.) were observed at 100 mg/kg/day. Early postnatal effects on the offspring were considered likely secondary to the effects in maternal animals around the time of parturition. At 100 mg/kg/day, weight gain in pups was depressed throughout lactation, with statistically significantly decreased weights noted toward the latter half of the lactation period. There were no treatment-related effects on adults or their offspring at 3 or 10 mg/kg/day in either generation. Based on these results, spinosad is not considered a selective reproductive toxicant, (i.e., no effects on reproductive parameters were noted below a level that produced toxicity in the adults) and the no observed effect level (NOEL) for both parental and reproductive/perinatal toxicity was 10 mg/kg/day.

Animals↗

Reproductive effects of nonylphenol in rats after gavage administration: a two-generation study.

The potential reproductive toxicity of nonylphenol (NP) was assessed in a two-generation reproductive toxicity study. Groups of 25 male and female Crj:CD (SD) IGS rats were given NP by gavage at levels of 2, 10, or 50 mg/kg, and 25 males and females were given corn oil as controls. No adverse changes in clinical signs were observed in any rats throughout the study. Significant increases in the liver, kidney and pituitary gland weights in males, and decreases in thymus weight in males and in ovary weight in females were observed in the 50 mg/kg group. NP did not affect sperm characteristics or the estrous cycle at any dose administered. A significant increase in the TSH level was observed in males in the 50 mg/kg group. No adverse effects of NP on reproduction were found. At necropsy, no treatment-related alterations were observed in any organs including the reproductive tissues in any group. Histopathologic changes were found in the liver of male and female rats and kidneys of males in the 50 mg/kg group. The viability of offspring from postnatal day 0 to 4 in the 50 mg/kg group was reduced as compared with that in the controls, although growth was not affected by NP administration. On postnatal day 22, an increase in the serum FSH level and decrease in T(3) level for males, and decreases in LH and TSH levels and an increase in T(3) levels for females were observed in the 50 mg/kg group. NP did not affect the timing of preputial separation, while vaginal opening was accelerated in the 50 mg/kg group. No adverse changes were found in behavior or learning in the offspring of NP-treated groups. There were no treatment-related changes in any reproductive parameter, including estrous cycle, mating, fertility, delivery, and lactation, except for significant decreases in the numbers of implantation sites and live pups, and a significant decrease in ovary weight in the 50 mg/kg group. Kidney and liver weight were increased in males in the 50 mg/kg group. Histopathologic examination revealed changes in the liver of males and females of the 50 mg/kg group. No treatment-related changes were observed in the sperm characteristics. Hormone data should be interpreted cautiously until the findings are repeated and confirmed by further studies. These results of NP suggested that the no observed adverse effect level (NOAEL) on reproductive capacity is 50 mg/kg/day or greater in parent animals, and 10 mg/kg/day in the next generation under the present experimental condition.

Administration, Oral↗

Seasonal variations in plasma hormones and reproductive efficiency in early postpartum buffalo.

Investigations were carried out on twenty newly calved Murrah buffalo that were divided into two sets of ten each during winter (December to February) and summer (May to September). Recommended feeding and management practices were followed. Blood samples were collected on Days 0, 1, 2, 4, 6, 8, 15, 22, 29, 36, 43, 50 and 57 postpartum for hormone radioimmune assay (RIA). The values of reproductive parameters and hormone levels during winter and summer, respectively, were the following for uterine involution, 39.50 +/- 2.74 d and 32.50 +/- 3.01 d; first postpartum estrus interval, 70.10 +/- 9.62 d and 37.40 +/- 11.82 d; number of services per conception, 1.57 +/- 0.29 and 2.40 +/- 0.68; first service conception rate, 40 and 20 %, overall conception rate, 70 and 40 %; 13,14-Dihydro-15-keto prostaglandin F(2alpha) (PGFM), 1.78 +/- 0.26 ng/ml and 2.62 +/- 0.30 ng/ml; progesterone, 1.09 +/- 0.14 ng/ml and 0.65 +/- 0.77 ng/ml. A negative correlation (r = -0.83, P 0.05 ) was observed between PGFM and progesterone. Although, summer stress hastens uterine involution and first postpartum estrus interval, overall reproductive efficiency is impaired due to deficiency of progesterone, which is essential for embryo survival.

Journal Article↗

Effect of treatment with ivermectin on reproductive performance of yearling beef heifers.

To determine the effect of treatment with ivermectin on reproductive parameters, 78 fall-born, yearling heifers were allotted to either an ivermectin treatment group or to the control, non-treatment group. The heifers were treated in June and October when they were approximately 7 and 11 mo old, respectively. Ivermectin effectively lowered fecal egg counts in the treated heifers compared with that of the controls. In heifers that were maintained on a marginal plane of nutrition, treatment with ivermectin not only improved weight gains during each recording period but also hastened the onset of puberty and improved the pregnancy rate during a 60-d breeding season. The positive effect of ivermectin on these reproductive characteristics could not be explained by increased weight gain alone, because the correlation between weight gain and puberty was not significant. Treatment with ivermectin positively affected pelvic area but not uterine score when compared with those of the controls.

Journal Article↗

Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in male rats.

BACKGROUND: Lasofoxifene is a nonsteroidal selective estrogen receptor modulator (SERM) with greater than 100-fold selectivity against all other steroid receptors and is a potentially superior treatment for postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of lasofoxifene on male reproduction in rats in light of the known effects of estrogen modulating compounds on male reproductive ability. METHODS: Lasofoxifene was administered to adult male rats at doses of 0.1, 1, 10, and 100 mg/kg for 66-70 consecutive days. After 28 days of dosing, male rats were cohabited with untreated female rats. Female rats were euthanized on gestation day 14 and a uterine examination was carried out for evaluation of reproductive parameters and embryo viability. Male rats were euthanized after 66-70 days of dosing and epididymal sperm motility and concentration were assayed. The testes, epididymides, prostate, and seminal vesicles were weighed and microscopically examined. RESULTS: The duration of cohabitation was increased for 100 mg/kg males by 0.7 days. The number of males copulating and the number of implantation sites produced per copulation were reduced in the 10 and 100 mg/kg groups. Weights of the seminal vesicles and epididymides were reduced for all groups, although the testes weight and epididymal sperm motility and concentration were not affected by treatment. There were no microscopic findings in the male reproductive tissues. CONCLUSION: The changes in male fertility and reproductive tissue weights after exposure to lasofoxifene are consistent with those previously described for estrogen receptor-modulating compounds.

Animals↗

A two-generation reproductive toxicity study of decamethylcyclopentasiloxane (D5) in rats exposed by whole-body vapor inhalation.

This two-generation reproduction study assessed the reproductive hazard potential of decamethylcyclopentasiloxane (D(5)). Sprague-Dawley rats (30/sex/group) were exposed by whole-body vapor inhalation to a target concentration of 30, 70, or 160 ppm D(5) or filtered air for 6h/day. Exposures for the F(0) and F(1) generations started at least 70 days prior to mating and lasted through weaning of the respective pups on postnatal day (PND) 21. Female exposures were interrupted from gestation day (GD) 21 through PND 4 to allow for parturition and to permit continuous maternal care for the early neonates. F(2) pups were not directly exposed to D(5). There were no exposure-related mortalities, clinical signs of toxicity, or effects on body weight or food consumption. There were no treatment-related gross findings or organ weight effects at the F(0) and F(1) necropsies. Other than minimal alveolar histiocytosis in all exposed groups, there were no noteworthy microscopic findings. Reproductive parameters (number of days between pairing and mating, mating and fertility indices, gestation length, and parturition), spermatogenic parameters and ovarian primordial follicle counts and numbers of corpora lutea in the F(0) and F(1) parental animals were not significantly changed between treated and control groups. Mean live litter sizes, number of pups born, sex ratios, pup body weights, postnatal pup survival and general physical condition of offspring in each generation were not affected. The slight, but statistically significant, increase in the mean F(1) male pup AGD in the 160 ppm group was not considered to be related to treatment. Vaginal patency and balanopreputial separation were unchanged compared to controls. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) for parental and reproductive toxicity was determined to be 160 ppm D(5).

Administration, Inhalation↗