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1.
2.
Effect of estradiol-filled polydimethylsiloxane subdermal implants in adult male rats on the reproductive system, fertility, and progeny outcome 总被引:1,自引:0,他引:1
Combinations of testosterone and estradiol have been proposed as potential male contraceptives. For any compound to be an acceptable male contraceptive, it must be demonstrated either to prevent pregnancy completely or, if contraceptive failure occurs, to not have any adverse effect on pregnancy outcome. We have previously established that increasing doses of testosterone given via subdermal implants to adult male rats will decrease spermatogenesis and fertility but will not result in an increased incidence of pre- or postimplantation loss or in abnormal progeny. In the present study, we have monitored the effects of a dose of estradiol that has been proposed for the contraceptive regimen, as well as doses three and seven times as large, on progeny outcome. Adult male Sprague-Dawley rats received s.c. implants of estradiol-filled polydimethylsiloxane capsules of varying lengths and, after three months, were each mated twice to two females in proestrus. The smallest dose of estradiol (the dose used in the contraceptive formulation) did not have any significant effects on any of the measured parameters of the male reproductive system, or on the incidence of pre- or postimplantation loss or on progeny outcome. With increasing doses of estradiol, there was a marked reduction in fertility. This reduction in fertility was not associated with a sufficient decrease in epididymal sperm reserves to account for the decrease in number of females impregnated, but was associated with a major reduction in seminal plugs; this would suggest that the large doses of estradiol were decreasing male sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Treatment of the father with the anticancer alkylating agent cyclophosphamide has negative effects on embryonic development in the rat. Four-week treatment of male rats with a low dose of cyclophosphamide causes a dramatic, dose-dependent increase in postimplantation death of the progeny. Several recent studies have indicated that the paternal genome is required for the development of the extraembryonic tissues. Thus, the purpose of this study was to determine which tissues of the implanting embryo were affected by paternal exposure to cyclophosphamide. Male Sprague-Dawley rats were given cyclophosphamide (6 mg/kg/day) or saline by gavage and bred to untreated female rats after 4 weeks of treatment. Pregnant female rats were killed on day 7 of gestation, and implantation sites were dissected from the uterus, fixed, embedded in Epon for semithin serial sectioning, and stained for subsequent light microscopy. Strikingly, many of the implantation sites of affected embryos sired by treated males displayed an apparently normal trophectoderm enclosing a region of dying cells, containing dark-stained pyknotic nuclei. Very few or no inner cell mass-derived embryonic cells were present in these implantation sites. Therefore, there is a selective death of inner cell mass-derived cells in day 7 implantation sites obtained from the progeny of cyclophosphamide-treated males. The results of this study suggest that treatment of the male with cyclophosphamide can affect paternal genes specifically required for development of the inner cell mass cells of the embryo, without an apparent effect on those genes required for normal trophectoderm. 相似文献
4.
A rapid assay for measuring the activity and the Mg2+ and Ca2+ requirements of phosphatidate phosphohydrolase in cytosolic and microsomal fractions of rat liver.
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1. A rapid extraction and purification scheme was designed for the recovery of [3H]diacylglycerol formed during the assay of phosphatidate phosphohydrolase. 2. The importance of removing polyvalent cations, particularly Ca2+, from the phosphatidate and other reagents used in the assay of the phosphohydrolase activity was demonstrated. This was achieved mainly by treating the phosphatidate with a chelating resin and by adding 1 mM-EGTA and 1 mM-EDTA to the assays. 3. The activity of the phosphohydrolase in dialysed samples of the soluble and microsomal fractions of rat liver was very low. 4. Addition of optimum concentrations of MgCl2 resulted in a 110-167-fold stimulation in activity. 5. CaCl2 was also able to stimulate phosphohydrolase activity, but to a much smaller extent than MgCl2. 6. Chlorpromazine, an amphiphilic cation, inhibited the reaction when it was measured in these experiments by using a mixed emulsion of phosphatidylcholine and phosphatidate at pH 7.4. 7. Microsomal fractions that were preincubated with albumin contained very low activities of the Mg2+-dependent phosphohydrolase. When these were then incubated with the soluble fraction in the presence of oleate, the soluble phosphohydrolase attached to the microsomal membranes, and it retained its high dependency on Mg2+. 相似文献
5.
B F Hales 《Teratology》1989,40(1):11-20
Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects of phosphoramide mustard are very similar to those of "activated" cyclophosphamide (4-hydroperoxycyclophosphamide). 相似文献
6.
Fever and regional blood flows in wethers and parturient ewes 总被引:1,自引:0,他引:1
Blatteis C. M.; Hales J. R.; Fawcett A. A.; Mashburn T. A. Jr 《Journal of applied physiology》1988,65(1):165-172
To determine whether the reported absence of fever in full-term-pregnant ewes might be associated with shifts of regional blood flows from thermogenic tissues to placenta during this critical period, fevers were induced twice by injections of Escherichia coli lipopolysaccharide (LPS, 0.25 microgram/kg iv) into each of six Merino ewes from 8 to 1 days prepartum, and their regional blood flow distribution was measured with radioactive, 15-microns-diam microspheres before and during the rise in fever (when their rectal temperature had risen approximately 0.4 degree C). Unexpectedly, fever always developed, rising to heights not significantly different at any time before parturition [4-8 days prepartum = 0.81 +/- 0.23 degree C (SE); 1-3 days prepartum = 0.75 +/- 0.17 degree C) and similar to those in three wethers treated similarly (0.90 +/- 0.10 degree C). Generally, during rising fever, blood flow in the ewes shifted away from heat loss tissues (e.g., skin, nose) to heat production tissues (e.g., shivering muscle, fat) and cardiac output increased; blood flow through redistribution organs (e.g., splanchnic bed) decreased. The reverse occurred during defervescence. Utero-placental blood flow remained high in the febrile ewes. These regional blood flow distributions during febrigenesis and lysis are essentially the same as those during exposures to ambient cold and heat, respectively. Some differences in the responses of cardiac output and its redistribution, however, were apparent between wethers and pregnant ewes. We conclude that 1) the previously reported "absence of fever in the full-term-pregnant sheep" should not be regarded as a general phenomenon and 2) full-term-pregnant sheep support fever production without sacrificing placental blood flow. 相似文献
7.
Suppression of spermatogenesis by testosterone in adult male rats: effect on fertility, pregnancy outcome and progeny 总被引:1,自引:0,他引:1
The relationship between decreasing spermatogenic activity and fertility, pregnancy outcome and the progeny is poorly understood. To study this relationship a model where testosterone is given by a sustained release device is used. Adult male Sprague-Dawley rats received empty or testosterone-filled implants measuring 0.5, 1.0, 2.0, 3.0, 4.0 and 8.0 cm. On Day 90 and again on Day 104 each male was exposed to two females in proestrus. Twenty days later the females were killed. Corpora lutea, implantation sites, resorptions and live normal and abnormal fetuses were counted. Sperm counts in the caput-corpus region of the epididymis in the 3.0-, 4.0- and 8.0-cm testosterone treatment groups were 12.6%, 3.0% and 29.9% of control, while those in the caudal region were 19.8%, 4.0% and 50.8% of control, respectively. The number of females with spermatozoa in the vagina after breeding was significantly diminished only in animals treated with the 4.0-cm testosterone implants (control, 95.8%; 4.0-cm, 50%) while the number of pregnant females per sperm-positive females was markedly reduced in the females mated with both the 3.0-cm and 4.0-cm testosterone implants (control, 82.6%; 3.0-cm, 10.0%; 4.0-cm, 7.7%). There was no effect on the numbers of corpora lutea, on the incidence of pre- or post-implantation loss, malformations, or on the numbers of pups/litter. Individual animals with a decrease in caudal epididymal spermatozoal reserves to less than 5 million, however, are infertile. A decrease in epididymal spermatozoal reserves mediated by testosterone does not cause an increase in teratogenicity in the resultant progeny. 相似文献
8.
When adult apterous viviparous females of Myzus persicae, reared in short night conditions at 21–23°C, are treated with the precocene analogue 6-methoxy-7-ethoxy-2,2-dimethylchromene, they deposit males towards the end of their reproductive lives. The first-born normal daughters of the treated females also deposit some males at various times in their reproductive lives. Karyotypic analysis was used to investigate the sequence of male and female embryos in the ovarioles of precociously metamorphosed aphids. The experiments support the hypothesis (Mittler et al., 1979) that juvenile hormone level controls the sex determination process in aphids. Since male aphids have an XO sex chromosome constitution, this implies that juvenile hormone level influences the behaviour of the X-chromosomes at or before the single maturation division of the egg. At this division one X-chromosome is eliminated from eggs which will develop as males. Aphids provide the first example of a specific endocrine influence on chromosome behaviour in sex determination. 相似文献
9.
The action of local anaesthetics on lipolysis and on adenosine 3′:5′-cyclic monophosphate content in isolated rat fat-cells 总被引:2,自引:1,他引:1
1. Local anaesthetics inhibited hormone-stimulated lipolysis in isolated rat fat-cells. The most potent anaesthetic was dibucaine, which inhibited adrenaline-stimulated lipolysis by 50% at a concentration of 0.16mm. 2. The amount of inhibition produced by a given concentration of anaesthetic was very similar with adrenaline, theophylline and dibutyryl cyclic AMP, at submaximal and maximal concentrations. 3. The inhibitory effect of dibucaine on lipolysis was apparent within 5 min and was constant over 1h. 4. Dibucaine inhibited basal, adrenaline-stimulated and insulin-stimulated glucose uptake at concentrations 6-10-fold higher than those inhibiting lipolysis. 5. The effects of dibucaine on lipolysis and glucose uptake were reversed after removal of anaesthetic and washing of cells. 6. Dibucaine further elevated the concentration of cyclic AMP in the presence of adrenaline or adrenaline plus theophylline. 7. Dibucaine had no effect on ATP content at concentrations causing 80% inhibition of lipolysis, but lowered ATP content at higher concentrations. 8. The relative potency of different local anaesthetics as inhibitors of hormone-stimulated lipolysis paralleled their potency as inhibitors of ion movements in other systems. 9. The possibility is discussed that Ca(2+) ions are involved in the regulation of lipolysis, and that local anaesthetics inhibit lipolysis by interfering with Ca(2+) translocation. 相似文献
10.