SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Successful human reproduction is a complex process which requires normal function of 2 individuals. Reproductive toxicants can impair reproduction by acting in the male, female or both. Reproductive toxicants can produce their adverse effects by several direct and indirect mechanisms. The mechanisms by which reproductive toxicants impair reproduction are reviewed.
We tested whether prevention of hibernation in ground squirrels by midwinter exposure to high ambient temperatures influenced timing of the spring phase of reproductive maturation and the phase and period of subsequent circannual rhythms of reproduction and body mass. Exposing hibernating adult male Spermophilus lateralis to 30 degrees C for 6 weeks beginning December 4 advanced the timing of testicular recrudescence by 4-5 weeks, compared to controls left at 4 degrees C. Males exposed to 30 degrees C for 6 weeks beginning at the average time of spontaneous end of hibernation (January 15) reached reproductive maturation at a time intermediate to those of controls and of the December 4 experimental group. However, neither the date of the subsequent fall's body mass peak, the date of the next year's reproductive maturation, nor the periods of circannual rhythms of body mass and reproduction differed among groups. Premature interruption of hibernation appears to allow early expression of reproduction, but does not affect the underlying timing mechanism.
1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappropriate for other effects (e.g. thyroid function and neurochemical effects). More data on a wider range of individual PCB congeners and a method for systematically balancing toxicodynamic and toxicokinetic data are required before the TEF approach can be fully evaluated. 3. With the exception of the teratogenic effects seen in mice and the anti-oestrogenic effects reported in in vitro studies, there are insufficient data on individual PCB congeners to evaluate the structure-activity relationships for the effects of PCBs on reproduction. The data also show that individual PCBs may have opposing effects on a particular aspect of reproduction (for example individual PCB congeners may have either oestrogenic or anti-oestrogenic effects). Studies with individual PCB congeners have shown both enhancement and antagonism of the teratogenic effects of 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) in the mouse. It is not possible to use TEFs to evaluate the reproductive effects of PCBs. 4. The mechanism(s) responsible for the effects of PCBs on postnatal neurobehavioural development in rodents and monkeys have not been elucidated. At least two groups of PCBs which might be responsible for the observed effects have been identified in this review, one affecting the dopaminergic system and the other group affecting thyroid hormone levels. Considerably more research would be required before the TEF approach could be applied to the effects of PCBs on postnatal neurobehavioural development. This would include research on an appropriate animal model to determine whether the critical toxicological mechanism is mediated through the Ah receptor. 5. The reproductive toxicity of complex PCB mixtures such as those found in foods will depend on the identifies and relative proportions of individual PCB congeners in the mixture. It is not possible to give an accurate estimate of a NOAEL or LOAEL from the reproduction studies using commercial PCB mixtures which could be readily applied to the safety assessment of PCBs present as contaminants in food. 6. It is concluded that the data presented in this paper support the hypothesis that there is no satisfactory method derived from the available studies in laboratory animals for evaluating the potential risk of adverse effects on reproduction posed by contamination of foods with PCBs.
A series of four experiments was conducted to examine the previously described phenomenon that the thyroid gland is required for the breeding season to end in female sheep. Exp 1 tested the hypothesis that the thyroid is required because of its secretion of T4. Ewes thyroidectomized (THX) in the anestrous season either received T4 replacement or no further treatment; seasonal reproductive shifts were compared to those of thyroid-intact controls. All ewes were housed in conditions in which the end of the breeding season results from the expression of an endogenous annual rhythm. The ewes were ovariectomized and given constant-release estradiol (E) implants; reproductive state was assessed from serum LH levels to monitor seasonal shifts in response to E negative feedback. THX did not alter onset of the breeding season (LH rise) but, in the absence of T4 replacement, blocked its end (LH fall). T4 replacement reversed this effect of THX. Exp 2 tested the hypothesis that the thyroid is required only until the onset of the breeding season for reproductive activity to end at its normal time. THX after the breeding season began, however, sustained the elevation in LH, suggesting that the thyroid is required after reproductive onset for the breeding season to end. Exp 3 tested the hypothesis that THX causes a widespread disruption of steroid feedback responses. No effect of THX, however, was observed with respect to either the ability of an E rise to elicit the LH surge or the ability of E, or progesterone, to suppress LH secretion in the breeding season. Of the steroid feedback responses tested, THX altered only the seasonal shift in potency of E negative feedback. Exp 4 examined circulating T4 in thyroid-intact ewes over a 2-yr period. An annual cycle of serum T4 was detected; values reached a peak in winter (late breeding season) and a nadir in summer (late anestrus). Our findings support the concept that the thyroid gland plays a fundamental role in seasonal reproduction in the ewe. In this regard, secretion of T4 after the onset of reproductive activity is required for an endogenously generated change in the neuroendocrine axis that leads to an intensified E negative feedback and an end to the breeding season.
The steroid hormone progesterone plays a central role in the reproductive events associated with pregnancy establishment and maintenance. Physiological effects of progesterone are mediated by interaction of the hormone with specific intracellular progesterone receptors (PRs) that are expressed as two protein isoforms, PR-A and PR-B. Both proteins arise from the same gene and are members of the nuclear receptor superfamily of transcription factors. Since these two isoforms were identified in the early 1970s, extensive controversy has existed regarding the selective contributions of the individual PR proteins to the physiological functions of progesterone. During the past decade, significant progress has been made in this regard using two complimentary approaches. First, analysis of the structural and functional relationships of each isoform using in vitro systems has generated compelling evidence to support the conclusion that PR-A and PR-B have different transcription activation properties when liganded to progesterone. Second, the advent of gene-targeting approaches to introduce subtle mutations into the mouse genome has facilitated the evaluation of the significance of observations made in vitro in a physiological context. Selective ablation of PR-A and PR-B proteins in mice using these technologies has allowed us to address the spatiotemporal expression and contribution of the individual PR isoforms to the pleiotropic reproductive activities of progesterone. Analysis of the phenotypic consequences of these mutations on female reproductive function has provided proof of concept that the distinct transcriptional responses to PR-A and PR-B observed in cell-based transactivation assays are, indeed, reflected in an ability of the individual isoforms to elicit distinct, physiological responses to progesterone. In PR-A knockout mice, in which the expression of the PR-A isoform is selectively ablated (PRAKO), the PR-B isoform functions in a tissue-specific manner to mediate a subset of the reproductive functions of PRs. Ablation of PR-A does not affect responses of the mammary gland or thymus to progesterone but instead results in severe abnormalities in ovarian and uterine function, leading to female infertility. These tissue-selective activities of PR-B are due to this isoform's ability to regulate a subset of progesterone-responsive target genes in reproductive tissues rather than to differences in its spatiotemporal expression relative to the PR-A isoform. More recent studies using PR-B knockout (PRBKO) mice have shown that ablation of PR-B does not affect ovarian, uterine, or thymic responses to progesterone but rather results in reduced mammary ductal morphogenesis. Thus, PR-A is both necessary and sufficient to elicit the progesterone-dependent reproductive responses necessary for female fertility, while PR-B is required to elicit normal proliferative responses of the mammary gland to progesterone. This chapter will summarize recent progress in our understanding of the selective contribution of the two PR isoforms to progesterone action.
The choice of experimental animal can have a large impact on experimental results, an example is the anecdotal evidence suggesting that Dark Agouti (DA) rats have a lower reproductive capacity than other rat strains. In this paper we report on an investigation into male reproductive characteristics in three rat strains--Wistar, Sprague-Dawley (outbred strains) and DA (an inbred strain). Reproductive organ weights, blood testosterone levels and sperm counts were measured in mature age-matched male rats. DA animals had significantly smaller testis weights than the Sprague-Dawley and Wistar animals, and this did not appear to be related to the overall smaller body mass of the DAs. There were no differences between the three strains in testicular histology or sperm counts (per gram testis). Although there was also no significant difference in epididymal sperm count, the DA animals had a much greater variability in sperm count than the other strains. There were no differences in relative (to body weight) epididymal, seminal vesicle or ventral prostate weights or in the blood testosterone levels. These results suggest that differences in reproductive capacity in DAs are neither the result of morphological differences in the reproductive organs nor in circulating testosterone levels. Sperm production appears to be normal but the lowered testicular weight and variability in epididymal sperm counts suggests that there are other factors in the testicular or epididymal environment which alter male reproductive function.
Internationally, reproductive performance of dairy cattle is declining. Under the low production, pasture-based and seasonal calving system used in New Zealand, reproductive performance is also declining, but remains higher than for many other industries. The seasonal calving system requires a high level of reproductive performance to ensure a 365 day inter-calving interval. About 80% of cows are detected in oestrus and inseminated in the first 3 weeks of the seasonal breeding programme and have a conception rate of 55% to 65% to this first insemination. This results in approximately 75% and approximately 90% of cows being pregnant by 6 weeks and by the end of the breeding programme, respectively. However, reproductive performance is declining due to multiple factors including increasing herd size, reduced oestrus detection sensitivity and specificity, declining body condition score at calving and increased rate of body condition score loss postpartum. Continuing selection for increased milk production is also having negative effects on reproduction. The mechanisms by which high production and negative energy balance are reducing reproductive performance are becoming better understood. However, practical solutions for the problem are challenging for veterinarians and consultants, especially given the consumer preference for less interventions.
Traditionally, drug toxicity in the reproductive system has been a concern only as it affects fertility and fecundity in young individuals. The purpose of this report is to address the potential problem of synergy between drug actions and abnormal secretion of reproductive hormones that together produce disease in older individuals. Thus, reproductive toxicity has different, but no less serious implications in aging individuals. During aging, the coordinated function of elements within the reproductive neuroendocrine axis degrades. This change promotes atypical secretion of hormones producing abnormal responses in target organs and thus creates a condition with pathogenic potential. Certain drugs may contribute to reproductive toxicity in aging individuals either by accelerating the process of dysregulation and/or by synergizing with hormones to stimulate pathologic changes in target tissues. The geriatric population of the world is increasing, and since it consumes a proportionately larger percentage of drugs than younger groups, this novel form of reproductive toxicity may represent a problem in drug safety that warrants serious consideration.
Development of approaches to risk assessment for reproductive toxicity has aided in the critical evaluation of the scientific basis for interpretation of data and the description of assumptions underlying the process. In addition, it has helped to standardize, to the extent possible, the use of qualitative and quantitative data in the hazard identification and dose-response processes and to identify research needed to fill gaps in the available database. The standard study protocols for evaluating reproductive and developmental hazards include developmental toxicity studies and both short-term and longer-term reproductive studies. These study protocols have been in use for several decades, but development of risk assessment approaches has prompted the recommendation of additional end point measures to these protocols. These include evaluation of specific neurologic and behavioral function of offspring following prenatal and postnatal exposure, evaluation of sperm production and quality, reproductive organ weights, and more in-depth testicular histopathology in males, as well as measures of age at vaginal opening, vaginal cytology, oocyte toxicity, time to mating, gestation length, and reproductive organ weights in females. Current approaches to risk assessment in reproductive toxicity involve the determination of a no-observed-adverse-effect level (NOAEL) and the application of uncertainty factors (UFs) to account for differences between the experimental animal species and humans, variability in sensitivity within the human population, and other factors as necessary to derive the reference dose (RfD), or a specified RfD for developmental toxicity to account for the short period of exposure required.(ABSTRACT TRUNCATED AT 250 WORDS)
This summary report focuses on current studies on reproductive effects reported at the workshop on Perinatal Exposure to Dioxin-like Compounds and supporting data noted in the discussion. Recent laboratory studies have suggested that altered development (e.g., low birth weight, spontaneous abortion, congenital malformation) and reproductive health (e.g., fertility, sex organ development, reproductive behavior) may be among the most sensitive end points when examining the effects of dioxinlike compounds. Thus, future research should target the reproductive health of both males and females exposed postnatally and prenatally. Studies in humans are needed and are on-going. In animal models, postnatal exposure to dioxin or dioxinlike compounds has been associated with abnormal spermatogenesis and abnormal testicular morphology and size in males and with reduced fertility and endometriosis in females. In utero exposure may also produce profound reproductive consequences in both males and females including delays in sexual maturation, abnormalities in development of sexual organs, and abnormal sexual behavior. The mechanism by which dioxin-like compounds cause reproductive effects is not well delineated.
Although chemical exposure has been associated with reduced reproduction in certain North American fish, reptiles, and mammals, definitive cause-and-effect data are lacking in many instances. Because the increasing use and global transport of industrial chemicals pose significant risk to successful reproduction, methods should be developed that can define the geographic extent and magnitude of injury and risk to wildlife. Because industrial chemicals are articles of commerce, information about injury to wildlife has been contentious and too often ineffective in changing societal behavior. The following strategies are advocated for inferring causal relationships. First, a balanced and comprehensive assessment of the data is necessary to determine the geographic extent of exposure and reproductive effects associated with environmental pollution. Initial efforts to document reproductive injury should focus on specific ecosystems in which detrimental effects have been observed, but lack sufficient causal data. Model systems (including experimental mesocosms or field ecosystems) should be identified or designed that can adequately test multigenerational reproductive effects. Mechanistic data from supportive laboratory studies on reproductive toxicity, quantitative structure-activity relationships, and bioaccumulation can be used to predict effects of related pollutants and to determine risk. Such information is essential to prevent future injury to wildlife and to prioritize the numerous remediation decisions facing our society.
This paper explores the social contexts of reproductive decision making among poor African-American women in inner-city distressed households by focusing on women's narratives of their reproductive and maternal experiences. We explore the hidden agendas and motivations that underpin women's reproductive decisions and perceived choices within the turmoil of poverty, domestic instability, economic uncertainty, and addiction. The political economy of reproduction, within which birthing and motherhood in distressed inner-city households take place, generates the conditions for absent fathers, brittle unions, and a highly skewed gendered division of parenting. Locally constituted notions of gender, agency and autonomy are key dimensions in the cultural constructions of motherhood in these female headed households. Woven into the local maternal experiences is also the desire to 'give and receive love'. By focusing on women's own formulations of responsibility and agency in their reproductive decisions, we can see how they make sense of their reproductive histories and maternal experiences amidst the constraints of poverty, class, race, and substance abuse.
Differences in the ways in which males and females maximize evolutionary fitness can lead to intra-locus sexual conflict in which genes delivering fitness benefits to one sex are costly when expressed in the other. Trade-offs between current reproductive effort and future reproduction and survival are fundamental to the evolutionary biology of ageing. This leads to the prediction that sex differences in the optimization of age-dependent reproductive effort may generate intra-locus sexual conflict over ageing rates. Here we test for intra-locus sexual conflict over age-dependent reproductive effort and longevity in the black field cricket, Teleogryllus commodus. Using a half-sib breeding design, we show that the most important components of male and female reproductive effort (male calling effort and the number of eggs laid by females) were positively genetically correlated, especially in early adulthood. However, the genetic relationships between longevity and reproductive effort were different for males and females, leading to low genetic covariation between male and female longevity. The apparent absence of intra-locus sexual conflict over ageing suggests that male and female longevity can evolve largely independently of one another.
Long-term cycles in diameter of the testes, colouration of the sexual skin and plasma concentrations of testosterone, FSH and prolactin were monitored in groups of pinealectomized (PINX), superior cervical ganglionectomized (SCGX), and control Soay rams living near Edinburgh (56 degrees N). In Exp. 1, PINX, SCGX and control rams were kept outside for 4 years, and well defined seasonal cycles in each of the reproductive parameters were evident in all 3 groups (e.g. testosterone cycle length assessed by sine-wave analysis: 12.08 +/- 0.17, 12.39 +/- 0.14 and 12.15 +/- 0.10 months for PINX, SCGX and control rams respectively). Qualitative differences, however, were apparent between the groups in the timing and amplitude of the reproductive cycle. The seasonal peak in reproductive function occurred from July to September in the PINX and SCGX rams, some 2 months earlier in the year than in controls, while the amplitude of the cycle was less marked in the PINX and SCGX rams. There were no significant differences between the experimental groups in the seasonal cycle in the plasma concentrations of prolactin. In Exp. 2, SCGX and control rams were kept indoors under an artificial environment with a 32-week light cycle and constant nutrition for 4 years. Compared to the controls, in which the reproductive changes were synchronized to the driving light cycle, the SCGX rams showed poorly defined reproductive cycles of lower amplitude and longer period (e.g. testosterone cycle length: 57.8 +/- 6.1 and 32.1 +/- 0.2 weeks for SCGX and control rams, respectively). There was evidence of a cycle in some of the reproductive parameters in the SCGX rams with a period close to 32 weeks during the second half of the study (e.g. testosterone cycle 32.4 +/- 0.8 weeks), which was taken to indicate social induction from the neighbouring control rams. In two further short-term experiments, SCGX rams showed a decline in testicular activity in response to receiving a restricted diet (60% of controls) and an increase in testosterone secretion in response to exposure to oestrous ewes. The overall results illustrate that PINX and SCGX rams can generate long-term synchronized cycles in pituitary and testicular activity. The animals are apparently unable to respond to changes in daylength due to the loss of the functional pineal gland but they remain competent to respond to other environmental cues such as changes in nutrition, temperature and social factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Ovaries were collected from 26 Ross seals shot in the King Haakon VII Sea south of the 60 degrees latitude during 3 periods, between 12 January and 2 February 1980-1982. The structure of the ovaries resembled that of other pinnipeds. A corpus luteum was found in 18 of 26 females, which therefore were regarded as reproductive. However, no females were lactating or visibly pregnant (presence of fetus in the uterus). Of the remaining 8 females (non-reproductive), 3 had neither a corpus luteum nor a corpus albicans. Ovulation did not alternate between ovaries in 4 of 10 females. Ovarian weight was greater in reproductive females than in non-reproductive females, and was also correlated with presence of a corpus luteum. Follicular development was more advanced in reproductive females than in non-reproductive females, and it was also more pronounced in the ovary containing a corpus luteum. The finding of a high percentage of females with a corpus luteum, but with no fetus in the uterus, together with histological characteristics of the ovarian structures in the present study, and earlier published data on mating, pupping and moulting, provide circumstantial evidence for delayed implantation in Ross seals.
Red deer stags were treated with melatonin implants in 2 experiments designed to examine the control of reproductive seasonality. In Exp. 1, stags (n = 24) were allocated to 4 treatment groups: 2 groups were treated with 3 implants per stag each month from 8 November to 5 February (EM) or 9 December to 5 February (LM), 1 untreated group of control stags remained with the melatonin-treated stags (CC) and the other untreated control group remained isolated (IC). Melatonin treatment advanced the seasonal changes in scrotal circumference, liveweight, antler state and coat type compared with control stags. The extent of advancement was greater in EM than LM stags. In EM and LM stags, size of testes regressed rapidly and antlers were cast shortly after melatonin implants became exhausted in March. This was followed by an additional antler cycle and reproductive development and decline from June to November. EM and LM stags became synchronized with control stags 14-15 months after melatonin treatment began. The extra cycle of seasonal changes was more pronounced in EM than in LM stags. In Exp. 2, stags (n = 30) were allocated to 6 treatment groups: 4 groups were treated with 3 implants per stag at monthly intervals for 6 months from 22 June (J), 4 August (A), 16 September (S) and 23 October (O), a further group of stags was treated in the same manner for 12 months from 22 June (Y), and the remaining group was untreated (C). Compared with control stags, testicular regression and antler casting was delayed in Groups J, A and Y. These events occurred at the same time as in control stags in Groups S and O. Subsequent reproductive development was advanced in Groups S and O and delayed in Groups J, A and Y. The results demonstrated that treatment with melatonin implants in November or December advanced reproductive development. However, when stags were treated with melatonin implants from June to August, reproductive development was delayed, indicating a change in response to melatonin treatment during the year. The change in response to melatonin treatment between late winter and early spring was interpreted as a resetting of an endogenous circannual rhythm caused by a photoperiodic cue responsible for initiating the final stages of reproductive regression.
Female reproductive success varies with social rank in many gregarious mammals, including primates, ungulates and carnivores. Social groups of spotted hyaenas (Crocuta crocuta) are structured by hierarchical dominance relationships that determine individuals' priority of access to food and other resources. The influence of female social rank on several measures of reproductive success was examined in a population of free-living Crocuta in Kenya. The study population was continuously observed for seven years, making it possible to document litter sizes, interbirth intervals, ages of cubs at weaning, intervals between weaning one litter and conceiving the next, annual rates of production of cubs, and survival of offspring to reproductive maturity. The relationship between availability of food, social rank, and female fertility was examined by monitoring abundance of prey throughout the study period. Most measures of reproductive performance were strongly influenced by social rank. High-ranking females began breeding a younger ages, were more frequently able to support pregnancy and lactation concurrently experienced shorter intervals between litters, and produced more surviving offspring than did lower-ranking females. Low-ranking females exhibited better reproductive performance when prey animals were abundant than when prey were relatively scarce. By contrast, reproductive performance among high-ranking females was always superior to that exhibited by low-ranking females, and did not vary with prey abundance. Fertility among high-ranking females thus appeared to be less vulnerable to fluctuations in the food supply than was that among low-ranking females.
Effects of age at first-pairing on the reproductive performance of the gerbil were studied throughout the reproductive life. Six groups of 7-30 female gerbils were paired monogamously with males at different ages. Out of 101 pairs in 6 groups, 79 (78.2%) produced 1 or more litters. The mean litter size at birth and mean weaning rate of 846 litters were 4.4 (totally 3,733 pups) and 67.4% (2,517 pups), respectively. Reproduction was compared in the 6 age groups. The littering rate (No. of females with litters/No. of female paired) was significantly lower in two groups in which mature females were paired with age-matched males (Group 4) or the oldest females with younger, sexually mature males (Group 6). The interval from pairing to the first litter was shortest in two groups in which mature females were paired with one month older, sexually mature males (Groups 3 and 5). Although the oldest pairs (Group 6) produced about 7 litters, the pairs from the other 5 groups produced about 10 or more litters throughout their reproductive life. The weaning rate was significantly higher in Group 6 (the oldest pairs) than in the younger groups. The effects of parity on reproduction were estimated from the data for the 61 pairs which produced more than 8 litters in the 6 groups. The number of pups at birth and the weaning rate were decreased in last 20-30% of the total parity in all 6 groups, although the age at the last litter in all groups was significantly different. The data suggest that any decline in reproduction may be due to not age but parity in the Mongolian gerbil.