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Modes of reproduction and the accumulation of deleterious mutations with multiplicative fitness effects.

Mutational load depends not only on the number and nature of mutations but also on the reproductive mode. Traditionally, only a few specific reproductive modes are considered in the search of explanations for the maintenance of sex. There are, however, many alternatives. Including these may give radically different conclusions. The theory on deterministic deleterious mutations states that in large populations segregation and recombination may lead to a lower load of deleterious mutations, provided that there are synergistic interactions. Empirical research suggests that effects of deleterious mutations are often multiplicative. Such situations have largely been ignored in the literature, since recombination and segregation have no effect on mutation load in the absence of epistasis. However, this is true only when clonal reproduction and sexual reproduction with equal male and female ploidy are considered. We consider several alternative reproductive modes that are all known to occur in insects: arrhenotoky, paternal genome elimination, apomictic thelytoky, and automictic thelytoky with different cytological mechanisms to restore diploidy. We give a method that is based on probability-generating functions, which provides analytical and numerical results on the distributions of deleterious mutations. Using this, we show that segregation and recombination do make a difference. Furthermore, we prove that a modified form of Haldane's principle holds more generally for thelytokous reproduction. We discuss the implications of our results for evolutionary transitions between different reproductive modes in insects. Since the strength of Muller's ratchet is reduced considerably for several forms of automictic thelytoky, many of our results are expected to be also valid for initially small populations.

Data Interpretation, Statistical↗

Reproductive impact of congenital Müllerian anomalies.

This retrospective longitudinal study was undertaken in order to determine the incidence and reproductive impact of uterine malformations on women desiring to conceive during their reproductive years. A total of 3181 patients in whom the morphology of the uterus was ascertained by hysterosalpingography (HSG) and laparoscopy/laparotomy during the years 1980-1995 was included in the study. The population analysed included fertile, infertile and sterile patients. The overall frequency of uterine malformations was 4.0%. Infertile patients (6.3%) had a significantly (P < 0.05) higher incidence of Müllerian anomalies, in comparison with fertile (3.8%) and sterile (2.4%) women. Septate (33.6%) and arcuate (32.8%) uteri were the most common malformations observed. Each malformation was individually analysed in fertile and infertile patients, in order to ascertain its actual reproductive impact. The performance of the unicornuate and didelphys uteri was similar with a chance of having a living child of 37-40%. The reproductive potential of the bicornuate uterus showed a live birth rate of 62.5% and the septate uterus showed a live birth rate of 62%. In all these abnormalities, early miscarriages (25-38%) and preterm deliveries (25-47%) were quite common. The arcuate uterus presented a live birth rate of 82.7%. It is concluded that uterine anomalies are relatively frequent in fertile women, and more frequent in infertile patients. Nevertheless, fertile patients with normal reproductive performance do exist, and Müllerian defects can permit an absolutely normal obstetric outcome. The reproductive performance of the unicornuate and didelphys uteri was poor, while that of the septate and bicornuate uteri was better than expected. The arcuate uterus had no impact on reproduction.

Abortion, Spontaneous↗

Neoplasms of the reproductive tract: the role of hormone exposure.

Cancers of the reproductive system are a major source of morbidity and mortality among women worldwide. Because the uterus, ovaries, and cervix are hormonally responsive tissues, exposure to endogenous or exogenous sex steroids can profoundly affect the carcinogenic process. Animal models developed to date provide valuable but imperfect systems in which to study neoplasms of the reproductive tract. Nonhuman primate models share the unique primate-specific endometrial physiology of humans, but rarely develop neoplasms of the reproductive tract. Therefore a surrogate marker approach is required for the study of hormonally induced cancer risk in primates. Rodents provide practical models in which tumorigenesis can be assayed in a short time and, with appropriate interpretation, can be used for assessment of risk, prevention, and therapeutic strategies. In addition to the spontaneous strain-dependent incidence of female reproductive cancers, the classical chemical and hormonal carcinogenesis models, and the use of xenograft approaches, novel genetically modified animals provide unique insights into relevant molecular mechanisms. Caveats in the use of rodent models include anatomical differences from the human reproductive tract, the greater possibility of different metabolic responses to hormonal agents than humans, strain variations in tumor type and hormonal responsiveness, and unexpected tumor phenotypes in genetically modified animals. Reported nonmammalian models are limited primarily to the study of ovarian carcinogenesis. Recent progress in the understanding of cervical carcinogenesis is encouraging. Unmet needs in this area of research include models of early events in ovarian carcinogenesis and strongly predictive models of endometrial cancer risk. Nonhuman primates remain indispensable for the study of some aspects of reproductive pathophysiology, but the best understanding of carcinogenesis in the reproductive tract requires a broad approach using complementary human, nonhuman primate, and nonprimate studies.

Animals↗

Maternal employment and reproductive risk factors.

Studies of reproductive hazards in the workplace must address potential biases related to selection for employment. The National Natality Survey, a probability sample of live births to married women in 1980, was used to examine the relation between female employment during pregnancy and factors that might affect reproductive outcome by analyzing the 5,927 women with complete occupational data. Demographic and behavioral attributes as well as reproductive history were compared for the 3,712 women employed and the 2,215 women not employed during pregnancy. Employed mothers were of more optimal reproductive age, were more highly educated, had higher incomes, began prenatal care earlier, had greater weight gain during pregnancy, and were slightly less likely to be heavy smokers. Employed women had markedly fewer previous births and less favorable reproductive histories (more stillbirths, miscarriages, and induced abortions) than unemployed women, controlling for gravidity. Full- and part-time workers were similar with regard to demographic and behavioral characteristics, but part-time workers had higher parity. Differences were noted by employment sector: professional women had especially favorable demographic and behavioral traits, and women employed as operatives and service workers were less advantaged. These results indicate that substantial differences in pregnancy-related risk factors exist in relation to employment, with working women generally having more favorable demographic and behavioral characteristics and less favorable reproductive histories. This pattern could produce selection bias in studies of work and reproductive health, and it encourages the restriction of comparison groups to other employed women, with a need to consider heterogeneity among working women as well.

Adult↗

Evolution of the expression of the Gld gene in the reproductive tract of Drosophila.

During the preadult development of Drosophila melanogaster, the GLD (glucose dehydrogenase) gene (Gld) is expressed in a variety of tissues, including the immature reproductive tract. At the adult stage the expression of Gld becomes largely restricted to the reproductive tract of males and females. We examined the expression of GLD in the adult reproductive tract of 50 species in the genus Drosophila, as well as in those of a few representative species from four other closely related genera. GLD exhibits considerable organ-specific diversity in the reproductive tract of males and females. Among these species, five male GLD phenotypes and six female GLD phenotypes were found. In contrast, the preadult expression of GLD in representative species from each distinct adult pattern type was determined and found to be highly conserved in both the immature reproductive tract and non-reproductive organs. Moreover, the set of reproductive organs that express GLD during preadult development is equivalent to the sum of the five male and six female adult GLD phenotypes. To initially define the contribution of cis- versus trans-acting factors responsible for differences in adult GLD expression between two of these species--D. melanogaster and D. pseudoobscura--we transferred the D. pseudoobscura Gld to the genome of D. melanogaster and investigated its expression. GLD expression patterns of these transformants displayed characteristics that are unique to both species, suggesting the presence of both cis- and trans-acting differences between these two species.

Age Factors↗

Variability in time reproduction: difference in ADHD combined and inattentive subtypes.

OBJECTIVE: To examine the relationship between time reproduction, performance variability, and sustained attention deficits in children with attention-deficit/hyperactivity disorder (ADHD) combined (ADHD-C) and inattentive (ADHD-I) subtypes, relative to matched controls. METHOD: Participants (age range 7.1-14.1 years) performed a time reproduction task. A subset of the ADHD group was also tested on the Sustained Attention to Response Test. Absolute discrepancy, accuracy coefficient, and intraindividual variability scores on the time reproduction task were compared across the three groups (ADHD-C: N = 20; ADHD-I: N = 19; controls: N = 44) and correlated with the Sustained Attention to Response Test. RESULTS: First, significantly better performance was observed in matched controls than in children with ADHD on the time reproduction task. Second, there was a significant difference between the two ADHD subtypes in the variability of the size of errors made at high time intervals (36-60 seconds). Third, intraindividual performance variability in the direction (over- versus underestimations) of time reproductions correlated with sustained attention performance. CONCLUSIONS: Children with ADHD varied more in the size and direction of their time reproduction errors than control children. Those with ADHD-C demonstrated more intraindividual variability than did those with ADHD-I in the size of their errors. The data provide support for a relationship between sustained attention and time reproduction. This relationship has previously been inferred from common right-lateralized neural circuitry that is thought to subserve these processes.

Adolescent↗

The significance of sperm nuclear DNA strand breaks on reproductive outcome.

PURPOSE OF REVIEW: A growing body of evidence indicates that ejaculated spermatozoa from men being treated with intracytoplasmic sperm injection contain nuclear abnormalities. Many of these nuclear anomalies manifest themselves as breaks in the sperm nuclear DNA. This review examines the mechanisms involved in generating DNA strand breaks during spermatogenesis in the human, the main techniques used to assess the sperm nucleus and the evidence, in relation to assisted reproduction, showing that sperm nuclear DNA strand breaks may impact on reproductive outcome. RECENT FINDINGS: Techniques such as the TUNEL assay and the sperm chromatin structure assay both show increased levels of DNA abnormalities in spermatozoa from men who have poor semen parameters. The reproductive parameters affected by an increased presence of DNA abnormalities in ejaculated spermatozoa include fertilization, blastocyst development, and pregnancy rates. SUMMARY: There is accumulating evidence linking sperm nuclear DNA anomalies to poor reproductive outcome in relation to assisted reproduction technologies. The tests currently available only provide an inkling of the impact of sperm nuclear DNA abnormalities on reproductive outcomes. Although the impact an abnormal paternal genome may have on reproductive outcome is unquestionably less than that of its female counterpart, it cannot be ignored.

Chromatin↗

Effect of shading individual soybean reproductive structures on their abscisic Acid content, metabolism, and partitioning.

Pod set in soybean is related to carbon partitioning and may be, at least partially, regulated by abscisic acid (ABA) concentrations. The studies reported here examine the relationship between carbon and ABA partitioning, reproductive abscission and ABA metabolism. The partitioning of radiolabeled ABA and photoassimilates from leaves to flowers and endogenous ABA concentrations were determined in shaded and unshaded reproductive structures. Aluminum foil was gently placed over individual soybean reproductive structures for 48 hours at 0, 4, 12, 17, and 22 days after anthesis (DAA). Shading of flowers at 12, 17, and 22 DAA resulted in significantly reduced concentration of ABA. However, shading had no effect on the catabolism of exogenously supplied [(3)H] ABA. The shading treatment on the first four of the five dates reduced partitioning of photoassimilates and ABA from the subtending leaf to the flower. Shading of reproductive structures also caused a significant reduction in the amount of assimilate exported from the subtending leaf, at 17 DAA. We conclude that shade-induced premature reproductive abscission in soybean is not stimulated by high levels of ABA within reproductive structures, but that ABA may inhibit abscission of reproductive structures by playing a role in preferential assimilate partitioning.

Journal Article↗

Reproductive rates in schizophrenic outpatients.

We investigated the marriage rates, the reproductive rates and the marital reproductivity of schizophrenic outpatients in Japan. A total of 553 patients with DSM-III-R-diagnosed schizophrenia at the Teikyo University Hospital, Tokyo, Japan were compared with age- and sex-matched outpatients at surgical clinics of the same hospital. Our findings indicate that the reproductivity of schizophrenics is reduced, even though the sample consists of outpatient population and modern operational diagnostic criteria have been used. The marriage rate and reproductive rate of the schizophrenics were reduced, especially in men. The number of married men was significantly less than that of married women and the reduced marital reproductivity was found in women but not men. These findings indicate that the reduced reproductivity of men in accounted for largely by a reduced rate of marriage, and that in women is accounted for partly by lower rate of reproductivity within marriage.

Adult↗

Dietary L-Tyrosine Sustains Egg Production and Quality by Modulating Promoter CpG Methylation, Gene Expression, and Hormone Profiles in Reproductive Signalling Pathways of Aged Laying Hens.

Managing prolactin (PRL)-mediated reproductive suppression is critical for maintaining egg production in commercial laying hens. L-tyrosine (TYR), a precursor of dopamine (DA), may counteract age-related reproductive decline by suppressing PRL, thereby sustaining productivity and egg quality in late-phase laying hens. The present study evaluated the effects of dietary L-tyrosine supplementation on laying performance, egg quality, reproductive hormone profiles, gene expression, and promoter CpG methylation in aged laying hens. A total of 180 Atak-S laying hens (71 weeks old) were randomly assigned to three dietary treatments, each with six replicates of 10 hens, and were fed a basal diet without L-tyrosine (control) or the basal diet supplemented with 0.5&#x2009;g/kg (TYR0.5) or 1&#x2009;g/kg (TYR1) L-tyrosine for 12 weeks. Hens in the TYR1 group exhibited higher hen-day egg production, improved feed conversion ratio, and significantly greater eggshell weight, shell thickness, Haugh unit, yolk index, and albumen index than the control group (p&#x2009;<&#x2009;0.05). Dietary L-tyrosine increased plasma DA and serum estradiol while reducing serum PRL (p&#x2009;<&#x2009;0.05). L-tyrosine also upregulated the expression of key dopaminergic and reproductive signalling genes, with corresponding promoter hypomethylation (p&#x2009;<&#x2009;0.05), whereas PRL mRNA expression tended to decrease with concurrent promoter hypermethylation. A significant negative correlation was observed between target gene expression and promoter CpG methylation levels (p&#x2009;<&#x2009;0.05). These findings indicate that dietary L-tyrosine modulates reproductive hormone profiles and molecular responses within reproductive signalling pathways, resulting in improved laying performance and egg quality. Therefore, L-tyrosine may represent a promising nutritional intervention to sustain reproductive function and productivity in late-phase laying hens.

Animals↗

A Wiener filter approach to the binaural reproduction of stereo sound.

This paper considers authentic binaural reproduction with loudspeakers using cross-talk cancellation. A systematic time domain deconvolution method is presented using both stochastic and deterministic Wiener filters. This method has advantages in that the Wiener filter is inherently causal and stable so that no additional stabilization process, as generally required in the frequency domain methods, is needed. Errors involved in the authentic reproduction are classified into modeling, inverse, and repeatability errors. In addition, the reproduction error is used as the performance measure of a reproduction system. Finally, a series of monaural and binaural reproduction tests were conducted in an anechoic chamber using a PC based reproduction system with a soundcard by changing the length of the inverse filter used. Test results demonstrated that the performance was improved in proportion to the length of the filter used. The reproduction performance error and its test procedure presented here can be used for objectively assessing the performance of a subjective auditory perception test system.

Journal Article↗

Sound-field reproduction in-room using optimal control techniques: simulations in the frequency domain.

This paper describes the simulations and results obtained when applying optimal control to progressive sound-field reproduction (mainly for audio applications) over an area using multiple monopole loudspeakers. The model simulates a reproduction system that operates either in free field or in a closed space approaching a typical listening room, and is based on optimal control in the frequency domain. This rather simple approach is chosen for the purpose of physical investigation, especially in terms of sensing microphones and reproduction loudspeakers configurations. Other issues of interest concern the comparison with wave-field synthesis and the control mechanisms. The results suggest that in-room reproduction of sound field using active control can be achieved with a residual normalized squared error significantly lower than open-loop wave-field synthesis in the same situation. Active reproduction techniques have the advantage of automatically compensating for the room's natural dynamics. For the considered cases, the simulations show that optimal control results are not sensitive (in terms of reproduction error) to wall absorption in the reproduction room. A special surrounding configuration of sensors is introduced for a sensor-free listening area in free field.

Journal Article↗

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract.

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350-353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

Animals↗

Regulation of VEGF in the reproductive tract by sex-steroid hormones.

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. In adults, angiogenesis is an infrequent event in the normal tissue except in the female reproductive tract where angiogenesis occurs frequently during the cyclical repair and regeneration of the endometrium as well as in the ovary. Little is known about angiogenesis in the male reproductive tract. The role of VEGF in controlling reproductive tract physiology and the role of hormones in regulating this key regulator of angiogenesis is not well understood. Since reproductive tract physiology is largely under sex-steroid regulation, we have reviewed some recent studies describing the role of sex-steroid hormones in regulating VEGF. We have also included studies on the role of sex-steroids in regulating VEGF and angiogenesis in endometrial, breast and prostate pathologies. We have provided an extensive review of the classical VEGF and VEGF receptors with examples drawn from numerous studies in the literature using diverse biological systems to encourage similar studies in the area of reproductive tract physiology. It is speculated that such studies will provide insights into understanding the role of VEGF in reproductive tract development, causes of infertility, and cancer. Such knowledge would allow us to target VEGF for improving human reproductive tract abnormalities, for enhancing implantation and fertility, and for designing drugs for treatment of endocrine dependent cancers.

Adult↗

Evolutionary expressed sequence tag analysis of Drosophila female reproductive tracts identifies genes subjected to positive selection.

Genes whose products are involved in reproduction include some of the fastest-evolving genes found within the genomes of several organisms. Drosophila has long been used to study the function and evolutionary dynamics of genes thought to be involved in sperm competition and sexual conflict, two processes that have been hypothesized to drive the adaptive evolution of reproductive molecules. Several seminal fluid proteins (Acps) made in the Drosophila male reproductive tract show evidence of rapid adaptive evolution. To identify candidate genes in the female reproductive tract that may be involved in female-male interactions and that may thus have been subjected to adaptive evolution, we used an evolutionary bioinformatics approach to analyze sequences from a cDNA library that we have generated from Drosophila female reproductive tracts. We further demonstrate that several of these genes have been subjected to positive selection. Their expression in female reproductive tracts, presence of signal sequences/transmembrane domains, and rapid adaptive evolution indicate that they are prime candidates to encode female reproductive molecules that interact with rapidly evolving male Acps.

Animals↗

Occupational exposure associated with reproductive dysfunction.

Evidence suggestive of harmful effects of occupational exposure on the reproductive system and related outcomes has gradually accumulated in recent decades, and is further compounded by persistent environmental endocrine disruptive chemicals. These chemicals have been found to interfere with the function of the endocrine system, which is responsible for growth, sexual development and many other essential physiological functions. A number of occupations are being reported to be associated with reproductive dysfunction in males as well as in females. Generally, occupations involving the manufacture/or application of some of the persistent chemicals that are not easily degradable as well as bio-accumulative chemicals, occupations involving intensive exposure to heat and radiation, occupations involving the use of toxic solvents as well as toxic fumes are reported to be associated with reproductive dysfunction. Occupational exposure of males to various persistent chemicals have been reported to have male mediated adverse reproductive outcomes in the form of abortion, reduction in fertility etc. with inconclusive or limited evidence. Nevertheless, there is a need for more well designed studies in order to implicate any individual chemical having such effects as in most occupations workers are exposed to raw, intermediate and finished products and there are also several confounding factors associated with lifestyles responsible for reproductive dysfunction. There is an urgent need to look at indiscriminate use of persistent chemicals especially pesticides and persistent organic pollutants (POP's) as these chemicals enter the food chain also and could be potential for exposure during the critical period of development. It is also necessary to impart information, and to educate about the safe use of these chemicals, as a very sensitive reproduction issue is involved with exposure to these chemicals. Occupational exposures often are higher than environmental exposures, so that epidemiological studies should be conducted on these chemicals, on a priority basis, which are reported to have adverse effects on reproduction in the experimental system.

Agricultural Workers' Diseases↗

Oestrogenic and antiandrogenic chemicals in the environment: effects on male reproductive health.

Exposures of human populations to pesticides and industrial pollutants, and to synthetic chemicals present in foods, beverages, and plastics, have raised concern that these substances can interfere with endogenous sex hormone function. Interference with sex hormone action can, in turn, result in a variety of developmental and reproductive anomalies. Compounds in this class are thus referred to as endocrine disruptors (EDs). EDs that affect reproductive processes in vertebrates act primarily by altering oestrogenic and antiandrogenic activities. The recent cloning of a second oestrogen receptor (ER) subtype (ERbeta) and its widespread tissue distribution pattern indicates that the first ER to be cloned, ERalpha, may not be the only, or even the primary, mediator of oestrogen action. It is anticipated that this discovery will lead to development of antagonist compounds specific to either ER subtype, and help to determine the function of each receptor subtype in reproductive and other tissues. Growing evidence suggests that EDs interfere with reproductive function at low exposure levels and cause distinct effects at different concentrations within the same organ. Developing organisms have increased susceptibility to the actions of EDs because differentiating tissues are more vulnerable to changes in hormonal milieu. Thus, children are at greater risk of toxicant-related illnesses than adults. However, most data are collected from laboratory studies, and it remains to be determined that the levels of chemicals in the environment can impair human reproductive health. There is also significant genetic variability between human and animal species in their reactions to chemicals. The effects of low-dose, chronic, and multiple chemical exposures warrant further investigation in order to characterize the risk of environmental agents to humans. The aims of this review, which will focus on male reproduction, are to: 1) identify synthetic chemicals in the environment that fall into the ED class; 2) describe their mechanisms of toxicity in reproductive tissues; and, 3) outline the direction of future research efforts with respect to EDs.

Androgens↗

Genetic relationships and additive genetic variation of productive and reproductive traits in Guernsey dairy cattle.

Data were first lactation production and reproduction records initiated from 1958 to 1981 in two experiment station Guernsey herds. Heritability estimates using paternal half sib groups were .24 +/- .12 for milk yield, .27 +/- .12 for fat yield, and .77 +/- .15 for fat percentage. Heritability estimates for reproductive traits ranged from .01 to .04 for number of services, service period, conception rate, and days open, but were higher for days in milk at first breeding (.12) and age at first calving (.13). Except for age at first calving, coefficients of additive genetic variation were larger for reproductive traits than for productive traits. Genetic correlations between measures of production and reproduction were moderate to large and antagonistic, except that the relationship between production and age at first calving was favorable. Breeding value estimates for milk yield and reproduction were negatively correlated for sires with above average breeding values for milk yield. Huge phenotypic variances for reproductive traits masked substantial additive genetic variation for these traits. When all things are considered it seems unwise to ignore reproductive performance in selection programs for dairy cattle.

Animals↗