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Reproduction in male Japanese quail exposed to microwave radiation during embryogeny.

Japanese quail (Coturnix coturnix japonica) embryos were exposed continuously to 2.45 GHz CW microwave radiation during the first 12 days of embryogenesis. The incident power density was 5 mW/cm2, and the specific absorption rate (SAR) was 4.03 mW/g. At 23 weeks of age an assessment of the reproductive capacity of the males was performed. Spermatozoal numbers and motility in semen samples which were collected manually were reduced significantly (P less than or equal to 0.01). However, spermatozoal viability and gross morphological characteristics in the exposed birds were not consistently different from the controls. Relative testicular weights were not altered significantly in the exposed males. Percentage of fertile eggs was significantly reduced when exposed males were mated to sham control females. The percentage of fertile eggs obtained from mating exposed males with sham control females was 72.5%, while the percentage of fertile eggs from mating of sham control males with sham control females was 80.4%. These data indicate that reproductive capacity in male Japanese quail is reduced when the birds are exposed to 2.45 GHz CW microwave radiation during embryogenesis.

Animals↗

Xenopus laevis is a potential alternative model animal species to study reproductive toxicity of phytoestrogens.

This study investigated effects of phytoestrogen quercetin on the gonadal development in Xenopus laevis. X. laevis at Nieuwkoop and Faber stage 46/47 were exposed to 50, 100 and 200 microg/L quercetin till 1 month postmetamorphosis. Gonads from frogs at 1 and 3 months postmetamorphosis were examined in gross morphology and histology. The highest dose of quercetin as well as estradiol (E2) significantly increased the percentages of phenotypic females. Exposure to quercetin at all doses induced abnormal testes with certain ovarian characteristics to some degree in gross morphology, including ovotestes. The abnormality rate exceeded 10% in each quercetin treatment. Histologic examination revealed that some abnormal testes exhibited intersexuality with testicular structure and ovarian structure or oocytes interspersed in testicular structure at 1 month postmetamorphosis. At 3 months postmetamorphosis, testicular abnormalities were more obvious, such as necrosis or apoptosis of spermatogonia, occurrence of developed or undeveloped oocytes, delay of the development of seminiferous tubes without or less late stage spermatocytes. The results have shown that quercetin cannot only feminize but also impair testicular development of X. laevis, i.e. X. laevis is sensitive to phytoestrogen. It is suggested that X. laevis might be an alternative model species to study reproductive toxicity of phytoestrogens.

Animals↗

Evaluation of the developmental toxicity of 2,3-dimercapto-1-propanesulfonate (DMPS) in mice. Effect on mineral metabolism.

The sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), a potent chelating agent used in the treatment of inorganic and organic heavy metal intoxications was evaluated for developmental toxicity in pregnant Swiss mice. DMPS was administered by gavage at doses of 0, 75, 150 and 300 mg/kg per day on gestational days 6-15. Females were evaluated for body weight gain, food consumption, appearance and behavior, survival rates and reproduction data. Cesarean sections were performed on gestation day 18. There were no maternal toxic effects, and no treatment-related changes were recorded in the number of total implants, resorption, the number of live and dead fetuses, fetal body weight or fetal sex distribution data. Gross external, soft tissue and skeletal examination of the DMPS-treated fetuses did not show significant differences at any dose in comparison with the controls. Mineral analysis of maternal and fetal tissues revealed slight effects of DMPS on metabolism of calcium, magnesium, zinc, copper and iron. The results of this study in mice indicate that DMPS is not a developmental toxicant at levels up to 300 mg/kg per day.

Abnormalities, Drug-Induced↗

Reproductive and teratological studies with a new aminoglycoside: netilmicin (Sch 20569).

Reproductive and teratological studies were undertaken with netilmicin (Sch 20569), a new semisynthetic aminolgycoside antibiotic structurally related to sisomicin. The administration of 32 and 80 mg/kg/day, by the intramuscular route, in the rat prior to and during pregnancy and lactation did not affect the fertility of animals, the resorptions rate and the vitality of the litters until the second generation. Also in the rabbit, the dose of 32 mg/kg/day by intramuscular route during pregnancy did not cause any embryotoxic effect. No gross malformations were observed in both species. The minor skeletal malformation, described as "wavy ribs", was observed at a significant level only in the rat foetuses generated by dams treated with a dose as high as 80 mg/kg/day by the intramuscular route.

Animals↗

Zambia mental health country profile.

This country profile for Zambia was compiled between 1998 and 2002. The objectives of the exercise were to first of all avail policymakers, other key decision makers and leaders in Zambia, information about mental health in Zambia in order to assist policy and services development. Secondly, to facilitate comparative analyses of mental health services between countries. The work involved formation of a core group of experts who coordinated the collection of information from the various organizations in Zambia. The information was later shared to a broad spectrum of stakeholders for consensus. A series of focus group discussions (FGDs) supplemented the information collected. There are various factors that contribute to mental health in Zambia. It is clear from the Zambian perspective that social, demographic, economic, political, environmental, cultural and religious influences affect the mental health of the people. With a population of 10.3 million and annual growth rate of 2.9%, Zambia is one of the most urbanized countries in sub-Saharan Africa. Poverty levels stood at 72.9% in 1998. In terms of unemployment, the most urbanized provinces, Lusaka (the capital city), and the copper-belt are the most affected. The gross domestic product (GDP) is US$3.09 billion dollars while per capita income is US$300. The total budget allocation for health in the year 2002 was 15% while the proportion of the GDP per capita expenditure for health was 5.6%. The HIV/AIDS prevalence rates stand at 20% among the reproductive age group 15-49 years. Political instability and wars in neighbouring states has resulted in an influx of refugees. Environmental factors affecting the country include natural and man-made disasters such as floods and drought, mine accidents, and deforestation. To a large extent in Zambia, people who are mentally ill are stigmatized, feared, scorned at, humiliated and condemned. However, caring for mental ill health in old age is positively perceived. It is traditionally the duty and responsibility of the extended family to look after the aged. Gender based violence (GBV) is another issue. Women, who are totally dependent on their spouses economically, are forced by circumstances to continue living in abusive relationships to the detriment of their mental well-being. In Zambia, the family is considered sacrosanct and the affairs of the family members, private. It is within this context that GBV is regarded as a family affair and therefore a private affair, yet spouse beating has led to depression and in some cases death. In terms of psychiatric services, there are close to 560 beds for psychiatric patients across the country. Common mental disorders found in Zambia are acute psychotic episodes, schizophrenia, affective disorders, alcohol related problems and organic brain syndromes. About 70-80% of people with mental health problems consult traditional health practitioners before they seek help from conventional health practitioners. Over time the number of frontline mental health workers and professional staff has been declining. This is due to the 'brain drain', retirement, death and low output from training institutions. For practicing psychiatrists, only one is available for the whole country. Other key mental health workers such as psychologists, social workers and occupational therapists are also in short supply. All in all, the mental health services situation in Zambia could be described as critical, requiring urgent attention.

Aged↗

Eight-year toxicity study in monkeys and reproduction studies in rats and rabbits treated with probucol.

Probucol [4,4'-(isopropylidenedithio)bis(2,6-di-tert-butylphenol)], a hypocholesterolemic agent, was given orally to male and female rhesus monkeys at 0, 60, 125, 250, and 500 mg/kg . d for more than 8 yr without adverse effect. Of 40 monkeys on test, 14 were killed for interim studies (wk 81 and 102), 21 were maintained for more than 8 yr, and 5 were submitted for necropsy for conditions unrelated to treatment. Monitored parameters included growth rate, demeanor, hematology, clinical chemistries, urinalyses, ophthalmoscopy, organ weights, and gross, histopathologic, and electron microscopic evaluations. Bone marrow smears at the conclusion of the test revealed no differences between control and treated animals. Electron microscopy of liver specimens from monkeys treated for 8 yr revealed comparable hepatocellular ultrastructure in control and treated monkeys. Probucol was given orally at 0, 100, 500, and 1000 mg/kg to Sprague-Dawley rats during appropriate time intervals to evaluate effects on fertility and postnatal development. The same dose levels were given during organogenesis, or in some cases prior to breeding and throughout organogenesis, to Sprague-Dawley rats and New Zealand white rabbits. No adverse effects on fertility or postnatal development were observed in rats, and no evidence of teratogenicity was observed in either species. The results indicate that probucol does not affect reproduction of rats, lacks teratogenic potential in the species studied, and is nontoxic to subhuman primates treated for more than 8 yr.

Abnormalities, Drug-Induced↗

Intrauterine infection of mice with St. Louis encephalitis virus: immunological, physiological, neurological, and behavioral effects on progeny.

Intravenous injection of pregnant mice with St. Louis encephalitis (SLE) virus at 8 days of gestation resulted in infection of the fetus. Progeny developed no antibody or tolerance to SLE virus since the viral antigen was cleared by maternal antibody before antibody-forming competence developed in the young. Temporary growth retardation was observed in a number of young at 3 weeks of age. After the initial setback the growth rate increased, indicating that early runting was due to an inability to adjust adequately to extrauterine life, which was subsequently overcome. In most other young there were no significant effects on growth, reproduction, or life expectancy. A few young died at or shortly after birth; in these, neurological changes ranging from gross defects such as encephaloceles and hydrocephalus to histological evidence of necrosis and congestion were observed. Neurologically related behavioral changes were detected by using the open field test and the rotating-rod test, which indicated neurological damage and memory impairment in the surviving intrauterinely infected animals.

Animals↗

Effects of diets containing gossypol on ovarian histology, function and fertility in prepubertal beef heifers.

Forty-five crossbred beef heifers (weight = 268.3 +/- 5.7 kg) were used to determine the effects of dietary gossypol on ovarian morphology, erythrocyte fragility and fertility. Heifers were randomly assigned to 1 of 3 isonitrogenous dietary treatments. The diet consisted of rice mill feed and milo supplemented with soybean meal (n = 13; control), cottonseed meal (n = 16; low supplementation) which supplied 6.1 g free gossypol animal(-1) day(-1), or whole cottonseed (n = 16; high supplementation) which supplied 13.7 g free gossypol animal(-1) day(-1). The heifers were group-fed each diet for 64 days and were maintained on similar but separate fescue pastures overseeded with wheat. After 64 days, 4 heifers from each diet were confined and fed their respective diets. On Day 10 following estrus, each animal was unilaterally ovariectomized, and the ovary containing the corpus luteum was removed. The remaining ovary was removed 6 to 12 hours after detection of estrus in the next cycle. Erythrocyte fragility increased (P < 0.02) in heifers receiving gossypol compared with that of the controls. Cyclicity in the heifers was 81.3, 68.8 and 38.4% for high, low and control diets, respectively, at the end of the 64-day treatment period. First service conception rate, as determined by palpation per rectum, was similar among treatments (58.3, 33.3, 33.3% for high, low and control groups, respectively). Weight gain increased (P < 0.03) in control heifers compared with that of heifers receiving gossypol. Gross ovarian morphology and histology were similar for all heifers. Although gossypol produced mild toxicosis in heifers, no adverse reproductive effects could be detected from gossypol intake.

Journal Article↗

Lack of teratogenicity of aluminum hydroxide in mice.

The embryotoxic and teratogenic potential of aluminum hydroxide, a therapeutic drug used as an antacid and phosphate binder, was investigated in Swiss mice. Mated female mice were given by gavage daily doses of 0, 66.5, 133 or 266 mg/kg of A1 (OH)3 on gestation days 6 through 15 and killed on gestation day 18. Females were evaluated for body weight gain, food consumption, appearance and behavior, survival rates, and reproduction data. No significant effects attributable to A1(OH)3 were noted in comparison of maternal body weight and food consumption values, appearance and behavior. No treatment-related changes were recorded in the number of total implants, resorptions, the number of live and dead fetuses, fetal size parameters or fetal sex distribution data. Gross external, soft tissue and skeletal examination of the A1-treated fetuses did not reveal differences at any dose in comparison with the controls. Thus, no evidence of maternal toxicity, embryo/fetal toxicity or teratogenicity was observed with A1(OH)3 in mice.

Aluminum Hydroxide↗

Obesity does not impact implantation rates or pregnancy outcome in women attempting conception through oocyte donation.

OBJECTIVE: To independently evaluate the effect of body mass index (BMI) on implantation, pregnancy, and incidence of spontaneous miscarriage using the donor oocyte recipient model. DESIGN: Institutional Review Board-approved retrospective data analyses of donor oocyte cycles from 1999 to 2004. SETTING: Private assisted reproductive technology (ART) center. PATIENT(S): Five hundred thirty-six first cycle recipients of donor oocytes. INTERVENTION(S): Data were collected from the first cycle of each donor oocyte recipient included in the study. The body mass index (BMI) of each recipient was calculated using the formula weight (in kilograms)/height (in meters squared). Patients were divided into four groups based on BMI: underweight, normal, overweight, and obese. Pregnancy outcomes in each group were compared. MAIN OUTCOME MEASURE(S): Body mass index, implantation rate, pregnancy rate (PR), miscarriage rate. RESULT(S): There were no statistically significant differences in the implantation rates, ongoing PRs, or spontaneous abortion rates among patients in the four BMI groups. When further divided into those patients receiving blastocyst vs. day 3 transfers, there was still no effect of BMI on implantation rate, PR, or loss rate among the blastocyst or day 3 donor oocyte recipients. CONCLUSION(S): Body mass index has no adverse impact on implantation or reproductive outcome in donor oocyte recipients. Therefore, obesity does not appear to exert a negative effect on endometrial receptivity.

Adult↗

Teratogenicity of Asparagus racemosus Willd. root, a herbal medicine.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Abnormalities, Drug-Induced↗

Embryonic and early fetal loss.

Embryonic and early fetal loss occurs in approximately one out of two pregnancies. Although this rate might appear unreasonably high, it is borne out by several types of studies and further confirmed by careful animal study. It now appears that karyotype deviation is common in early abortuses and probably underlies the high rate of gross abnormality seen in this group. In addition, environmental factors (radiation, smoking, anesthetics, and previous therapeutic abortion) may contribute to this wastage. Study and analysis of the abortus have allowed identification of a number of new embryonic and fetal syndromes. Careful description and classification combined with continued monitoring of abortuses shows promise both as an adjunct to reproductive counseling and as an important defense against teratogenic exposure. It is through this study that the etiology and ultimately the control of preventable pregnancy wastage will be understood and implemented.

Abnormalities, Multiple↗

Hydroquinone: a developmental toxicity study in rats.

To determine the potential developmental toxicity of hydroquinone (HQ), pregnant rats (COBS-CD-BR) were given 0, 30, 100, or 300 mg/kg HQ by gavage on the 6th through the 15th days of gestation. Maternal effects included a slight, but significant (p less than or equal to 0.05), reduction in body weight gain and feed consumption for the 300 mg/kg HQ dams. Reproductive indices, i.e., pregnancy rate, numbers of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, fetal sex ratio, pre- and postimplantation losses, and gravid uterine weights, were not affected by treatment with HQ. A slightly reduced (p less than or equal to 0.05) mean fetal body weight seen at the 300 mg/kg dose level was associated with the slightly reduced body weight gain seen for the dams at this dose level. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed no HQ-related malformations. The incidences of gross external variations (small hematomas) and internal soft tissue variations (dilated renal pelvis, hydronephrosis, and hydroureter) in the HQ-treated litters were not statistically different from the control incidences. Skeletal variations (delayed ossification of membranous skull bones, hyoid bone, thoracic centra 1-3, sacral arches 3 and 4, and bilobed thoracic centra 9-13) were seen with similar frequency in the control and HQ-treated groups. A statistically significant increase in the incidence of total common vertebral variations seen at the 300 mg/kg HQ dose level was not considered toxicologically significant. The incidences of total skeletal variations were not statistically different between the control and the HQ-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Quinacrine sterilization (QS) in Costa Rica: 694 cases.

OBJECTIVES: To evaluate the safety, efficacy and acceptability of quinacrine sterilization (QS) in Costa Rica. METHODS: From 1989 though August 1993, 694 women volunteered for QS in my private practice. All were referred by a family planning clinic or a local hospital obstetric service. The protocol used involved the transcervical insertion of 216 mg of quinacrine hydrochloride in the form of 6 pellets. A second dose was given 4 weeks later. All insertions were done in the first 14 days of the menstrual cycle. The procedure was similar to the CuT IUD placement. Temporary contraception was recommended for 3 months after the last insertion. The cut-off date for this analysis was April 1994. RESULTS: With 7 months to 5 years of follow-up, the gross pregnancy rate was 2.5%. Side effects were relatively minor, none requiring hospitalization. CONCLUSION: QS was found to be safe, effective and acceptable.

Adolescent↗

Congenital malformations and variations in reproductive performance in the ferret: effects of maternal age, color and parity.

Demographic data of ferrets from a commercial breeding colony were analyzed for the effects of maternal age, parity and strain on reproductive performance and the frequency of gross congenital abnormalities observed at parturition. Litter size (mean +/- SEM) was found to be greatest for young, primiparous females (10.3 +/- 0.2) and decreased with advancing maternal age and parity to a cohort mean of 8.1 +/- 0.1 for third parity females 16 months of age. Age, parity or strain had no effect on 24-hour neonatal mortality (7%) or mortality from birth to weaning (20%) and an examination of the causes for death suggested that these rates can be reduced. The malformation rate from two cohorts of females whelping at different times of the year was low (less than 1.0%) and not significantly different. A higher frequency of malformed offspring was detected in females of low previous parity (0-2) than in those with three or more. Based on data obtained in this survey, the ferret would seem a valuable alternative, nonrodent species for teratologic investigations using currently recommended protocols.

Animals↗

Postpartum evaluation of bovine reproductive potential: comparison of findings from genital tract examination per rectum, uterine culture, and endometrial biopsy.

The genital tract of 106 cows was evaluated after parturition by rectal palpation and by visual inspection of vaginal discharges. Analysis of these results revealed a significant (P less than 0.01) correlation with the ratings of endometrial biopsies. The most frequent bacterial isolations included Corynebacterium pyogenes, coliforms, or streptococci, or combinations thereof. Abnormal ratings obtained by gross evaluation and by histologic examination were associated principally with C pyogenes. Purulent discharges in particular were highly correlated (P less than 0.01) with infection caused by C pyogenes. Neither the gross genital tract condition nor the uterine histopathology rating was positively correlated with conception rate; however, the association between days open and conception rate was significant (P less than 0.05). Bacterial infections significantly (P less than 0.05) increased the number of services required for conception and significantly (P less than 0.01) increased the number of cows culled because of infertility. Cows up to 4 years old had a 61% 1st-service conception rate compared with 35% for older cows, and this difference was significant (P less than 0.05). The development of one or more postpartum diseases significantly (P less than 0.05) reduced 1st-service conception rate, whereas milk production was negatively correlated (P less than 0.05) with conception.

Animals↗

Controlled ovarian hyperstimulation and transvaginal intratubal insemination as an alternative to gamete intrafallopian transfer.

OBJECTIVE: To evaluate the efficacy of controlled ovarian hyperstimulation (COH) followed by intratubal insemination in the treatment of infertility. DESIGN: Retrospective analysis of 179 intratubal insemination trials in 78 women over a 48-month period. SETTING: Reproductive endocrinology practice. PATIENTS: Seventy-eight women, 26 to 44 years old (34 +/- 4.3 years; mean +/- SD), classified into subgroups according to diagnosis and age (< 40 or > or = 40 years). INTERVENTIONS: Patients underwent COH and intratubal insemination. MAIN OUTCOME MEASURES: The rates of pregnancy, delivery, spontaneous abortion, ectopic and multiple gestation, and complications were studied and analyzed statistically. RESULTS: Overall, there were 36 pregnancies (20.1% of 179 trials), 29 deliveries (16.2%), 5 of 36 first trimester abortions (13.9%), 2 of 36 ectopic pregnancies (5.6%), and 4 twin gestations. There were no serious complications. In 43 women < 40 years without male factor the first trial resulted in 15 pregnancies (34.9%); in 27 women < 40 years with male factor the first trial resulted in 4 pregnancies (14.8%). Male factor reduced significantly the probability of conception. In 19 women < 40 years of age with either ovarian dysfunction or infertility of unknown cause, the first trial resulted in 9 pregnancies (47.4%), which was significantly better than the 10 pregnancies achieved in the first trial in the remaining 51 women < 40 years of age. Peak serum E2 levels and number of mature follicles had a significant effect on pregnancy rates. CONCLUSIONS: Intratubal insemination yielded pregnancy rates comparable to those published for GIFT at reduced cost and with fewer complications.

Adult↗

Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations.

This study assessed reproductive performance, fetal viability and teratogenicity in female mice exposed to cyclophosphamide across a timeline corresponding to different stages of follicle maturation. Pregnancies were established in female Balb/c mice 1-4 weeks after administration of a non-sterilizing dose of cyclophosphamide (75 mg/kg). Each mating group represented a different stage of follicular growth at the time of cyclophosphamide exposure. The number of corpora lutea, pregnancies and fetal resorptions were determined. Surviving fetuses were evaluated for gross malformations. Results indicated that conceptions attributable to follicles exposed to cyclophosphamide at a mature stage had a significantly lower number of implantation sites, 4.82 +/- 1.01 versus 8.27 +/- 0.81 in controls (P = 0.001) and a high resorption rate, 56% +/- 0.11 versus 34% +/- 0.07 in controls (P = 0.05). The proportion of corpora lutea in this group which resulted in viable fetuses was extremely low, 0.2 +/- 0.06 versus 0.51 +/- 0.07 in controls (P = 0.001). Malformation rate was more than 10 times higher in all treated groups (P < 0.05) and a particularly high incidence of 33% (P = 0.0014) was observed in conceptions attributable to oocytes exposed to cyclophosphamide at the earliest stages of follicle growth. With an extended interval between exposure and mating the malformation rate gradually decreased towards normal values in the 12th week group. This study suggests that the effect of cyclophosphamide on female gametes and subsequently on future reproduction is influenced by the stage of oocyte maturation at the time of exposure. Early fertilization post-chemotherapy can result in a high rate of pregnancy failure and high malformation rate. This should be taken into account when considering the use of oocyte retrieval, IVF and embryo cryopreservation in patients currently undergoing chemotherapy.

Abnormalities, Multiple↗