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PubMed2003

Individual good and common good: a communitarian approach to bioethics.

The field of bioethics emerged in the late 1960s and early 1970s. Among its early issues were the protection of human research subjects, the rights of patients, abortion, and reproductive issues. Partly as a reflection of the times, and of those issues, the field became focused on autonomy and individual rights, and liberal individualism came to be the dominant ideology in the 1980s and 1990s. Communitarianism, as an alternative ideology focused more on the common good and the public interest than on autonomy, was a neglected approach. But many bioethical issues can not reasonably be reduced to questions of individualism and choice only. Issues of genetics and reproduction will of necessity touch on the society as a whole, its values, and its social institutions. Serious ethical analysis must take the social implications seriously and not simply assume that they should be left to autonomous choices of individuals. Human beings are social animals and our nature is distorted if we think of ourselves only as co-existing social atoms. Various approaches to communitarianism are outlined, and the question of the relationship between individual good and common good is confronted.

Bioethical Issues↗
PubMed2004

A short core promoter drives expression of the ALF transcription factor in reproductive tissues of male and female mice.

The control of gene expression in reproductive tissues involves a number of unique germ cell-specific transcription factors. One such factor, ALF (TFIIA tau), encodes a protein similar to the large subunit of general transcription factor TFIIA. To understand how this factor is regulated, we characterized transgenic mice that contain the ALF promoter linked to either beta-galactosidase or green fluorescent protein (GFP) reporters. The results show that as little as 133 base pairs are sufficient to drive developmentally accurate and cell-specific expression. Transgene DNA was methylated and inactive in liver, but could be reactivated in vivo by system administration of 5-aza, 2'-deoxycytidine. Fluorescence-activated cell sorting allowed the identification of male germ cells that express the GFP transgene and provides a potential method to collect cells that might be under the control of a nonsomatic transcription system. Finally, we found that transcripts from the endogenous ALF gene and derived transgenes can also be detected in whole ovary and in germinal vesicle-stage oocytes of female mice. The ALF sequence falls into a class of germ cell promoters whose features include small size, high GC content, numerous CpG dinucleotides, and an apparent TATA-like element. Overall, the results define a unique core promoter that is active in both male and female reproductive tissues, and suggest mouse ALF may have a regulatory role in male and female gametogenic gene expression programs.

Animals↗
PubMed2004

Primate models for assisted reproductive technologies.

Although the deliberate creation of human embryos for scientific research is complicated by ethical and practical issues, a detailed understanding of the cellular and molecular events occurring during human fertilization is essential, particularly for understanding infertility. It is clear from cytoskeletal imaging studies of mouse fertilization that this information cannot be extrapolated to humans because of unique differences in centrosomal inheritance. However, the cytoskeletal rearrangements during non-human primate fertilization are very similar to humans, providing a compelling animal model in which to examine sperm--egg interactions. In order to address this key step in primate fertilization and to avoid the complexities in working with fertilized human zygotes, studies are now exploring the molecular foundations of various assisted fertilization techniques in a monkey model. While intracytoplasmic sperm injection with ejaculated or testicular sperm is quite successful in primate models, there are some specific differences when compared with standard IVF that warrant further investigation, particularly in regards to nuclear remodeling, genomic imprinting, Y-chromosome deletions and developmental outcomes. Similarly, primate models have been useful for examining spermatid function during fertilization but these have met with limited success. One area of primate reproductive research that has yet to be mastered is reproductive cloning. Genetically identical primates would provide the ultimate approach for accelerating stem cell-based therapies for a number of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, as well as targeted gene therapies for various metabolic disorders.

Animals↗
PubMed2001

The reproductive biology of Polytrichum formosum: clonal structure and paternity revealed by microsatellites.

Using highly polymorphic microsatellite markers, we assessed clonal structure and paternity in a population of the bryophyte species Polytrichum formosum. Identical multilocus genotypes of individual shoots were almost never observed in spatially separated cushions, but were found to be highly clustered within moss cushions. Therefore, asexual reproduction through dispersal of gametophyte fragments is not very important in P. formosum. However, asexual reproduction on a very localized scale through vegetative growth of genets (branching of gametophytes via clonal growth of rhizomes) is very extensive. The patchy spatial distribution of genets and the absence of intermingling among genets suggest that this species follows a 'phalanx' clonal growth strategy. Vegetative proliferation of genets will increase their size, and, consequently, will have considerable fitness consequences for individuals in terms of increased genet longevity and reproductive output. Although paternity analysis of sporophytes confirmed male genet size, i.e. gamete production, to be an important determinant of male reproductive fitness, it also showed that the spatial distance to female genets is the predominant factor that governs male reproductive success. Moreover, we showed that male gamete dispersal distances in P. formosum are much further than generally assumed, and are in the order of metres rather than centimetres. Combining the findings, we conclude that the high genotypic diversity observed for this facultatively clonal species is most likely explained by a preponderance of sexual reproduction over clonal reproduction.

Bryopsida↗
PubMed2004

Differential reproductive efficiency associated with common apolipoprotein e alleles in postreproductive-aged subjects.

OBJECTIVE: To investigate the possible impact of apolipoprotein E (APOE) polymorphism on reproductive efficiency. DESIGN: Population study. SETTING: University Departments and a Laboratory of National Research Council. PATIENT(S): One hundred sixty healthy unrelated subjects of postreproductive age. INTERVENTION(S): Peripheral blood collection and questionnaire administration. MAIN OUTCOME MEASURE(S): Apolipoprotein E genotypes were detected after PCR amplification and CfoI digestion; plasma total cholesterol was assayed. RESULT(S): The mean number of children of e*2 allele carriers (2.4) was lower than that of e*3/e*3 and e*4/e*3 subjects (3.9). The trend was similar (2.8 vs. 4.8) when the number of pregnancies was considered. Moreover, there was a clear inverse relationship between number of children and e*2-carrying genotype proportions (chi(2) for trend = 6.3). Conversely, the e*3/e*3 genotype was associated with the highest number of children and pregnancies (3.9 and 4.9, respectively), and the e*4/e*3 genotype, with intermediate values (3.7 and 4.4). Carriers of e*2 allele also showed the lowest levels of total cholesterol. CONCLUSION(S): The e*2 allele seems to be associated with the lowest reproductive efficiency and the e*3 allele, with the highest. The different total cholesterol levels associated with APOE genotypes could have an effect on steroidogenesis and determine as a consequence the observed differential fertility.

Aged↗
PubMed2004

Early events in speciation: polymorphism for hybrid male sterility in Drosophila.

Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage.

Age Factors↗
PubMed2001

Whence meiosis?

Sexual reproduction predominates among eukaryotic organisms on our planet. While debate continues over why this should be so, burgeoning genomic and functional information now allows us to begin to think reasonably about some of the events that may have occurred to make sex possible in the first place.

Animals↗
PubMed1977

On the birth of an infant with sickle cell anemia.

This is the first report in the English literature of the birth of an obligate SS infant whose parents both had sickle cell anemia. The young adult SS parents of this infant and their families did not wish to prevent the birth of this child but had, in fact, many positive reasons to continue the pregnancy to term even in the face of the increased personal risk of pregnancy for this mother. This unusual circumstance initiated a re-appraisal of the realistic expectations with respect to reproduction in patients with homozygous recessive genetic disorders. No definitive studies could be found which attempted to evaluate the influence of genetic counseling on reproductive behavior in patients with sickle cell anemia. The questions raised about the 'right to reproduce' and the realistic aims of genetic counseling in adult homozygote patients have been discussed. However, no conclusions seem warranted because of the paucity of available information.

Adult↗
PubMed2002

High male reproductive success of hermaphrodites in the androdioecious Phillyrea angustifolia.

Androdioecy, the coexistence of males and hermaphrodites within a population, is a rare breeding system, often considered as unlikely to evolve because of restrictive conditions for its maintenance. Phillyrea angustifolia, a wind-pollinated shrub, is one of the handful species reported to be androdioecious. Our previous studies have shown that natural populations of this species in southern France exhibit higher male frequencies (approximately 50%) than predicted on theoretical grounds. Thus, the male functionality of hermaphrodites is still debated. To assess the functional breeding system of this species in the wild, a paternity analysis was performed with two highly polymorphic microsatellite loci on 729 seeds collected on 10 maternal shrubs in a natural population of 24 mature individuals of P. angustifolia. A large proportion of seeds were found to have been sired by pollen from outside the population. Analysis of seeds sired by individuals within the study population revealed a high male fertility of hermaphrodites resulting in a low male advantage in fertility for male plants. Intermate distances were found to have a strong impact on male reproductive success, whereas sexual morph had no effect, with males and hermaphrodites performing equivalently. This study is the first to unequivocally document the occurrence of a male function of hermaphrodites in a natural population of an androdioecious species.

Fertility↗
PubMed1993

New technologies and decision making in high producing herds.

New technologies have evolved for improved management of on-farm records and their use in decision making. Computerized on-farm record systems, coupled with automated monitoring of individual animal performance and electronic transfer of data between the on-farm database and mainframe systems, have enhanced the capability for herd management. Electronic aids for decision making may be embedded into on-farm management programs to allow more detailed data to be available with ease and convenience. Technological advances and their application toward improved operational decisions concerning production monitoring, reproductive management, genetic improvement, feeding, and health in a 300-cow dairy herd are presented as examples. Substantial advances have been made in technologies that improve management and decision making. Evolving technologies promise to enhance further the capabilities for improved management and decision making in high producing herds.

Animal Feed↗
PubMed2001

TestSmart-high production volume chemicals: an approach to implementing alternatives into regulatory toxicology.

This article examines the status and application of alternatives defined as replacements, refinements, and reduction for screening high production volume (HPV) chemicals. It specifically focuses on the Screening Information Data Set (SIDS), a series of toxicological tests recommended by the Organization for Economic Cooperation and Development to screen such chemicals. Alternative tests associated with acute, repeat-dose, genetic, and reproductive and developmental toxicity were examined at 2 meetings of academic, industry, and regulatory scientists and their status determined. Tests were placed in 1 of 3 categories: ready for immediate use, in need of or currently undergoing validation, or needing research/developmental work. With respect to traditional acute toxicity testing, the basal cytotoxicity approach was placed in the category of research with the up-and-down, fixed-dose, limit test, and the acute toxic class categorized as available for immediate use and the neutral red assay under validation. Cell culture methods that could provide information on acute target organ toxicity were all categorized in the research stage. Studies of the Ah receptor were placed under validation. All alternative tests for repeat-dose toxicity were placed in the category of research. With regard to genetic toxicity, the Ames, mouse lymphoma, and Chinese hamster ovary methods were considered ready for immediate use, while the in vitro micronucleus and Syrian hamster ovary assays were placed in the validation category. All alternatives for developmental toxicity, with the exception of gene chip technology, were placed in the category of validation. Gene chip technology is considered to be in the research stage. For reproductive toxicity, sperm motility and morphology were considered as ready for immediate use, with the other assays categorized as needing validation or in the research stage. Follow-up to these results is obvious. Work needs to be conducted to move those tests from the research stage to the validation and use stage. This is one approach to the development of alternatives to SIDS. Progress along these lines would apply not only to SIDS but also to toxicology in general.

Animal Testing Alternatives↗
PubMed2001

Expression of rolB in apomictic Hieracium piloselloides Vill. causes ectopic meristems in planta and changes in ovule formation, where apomixis initiates at higher frequency.

The effects of the Agrobacterium rhizogenes rolB oncogene on apomixis were examined in the facultative apomictic plant Hieracium piloselloides because the oncogene has been shown to alter plant growth, morphogenesis and cellular sensitivity to auxin. Introduction of rolB under the control of either its own promoter or the CaMV35S promoter induced ectopic meristem formation from the inflorescence, confirming in planta a meristem-inducing role for this oncogene previously observed only in tissue culture. These ectopic meristems formed vegetative rosettes and floral plant organs. Upon immersion in water these meristems generated roots, suggesting that meristem commitment towards the generation of a specific organ type is a separate and later event that is dependent upon the developmental context. Ovule identity and form was altered in ectopically induced florets in plants expressing the CaMV35S::rolB construct. In contrast to the ovules of untransformed apomictic plants, the sexual process ceased earlier, prior to meiosis, yet surprisingly, apomixis initiated from a greater number of cells, and embryos and endosperm continued to develop in the structurally altered ovules. The alternative possibilities that the effects on reproduction might result from rolB influencing cellular response to auxin, or from alterations in cell signaling caused by changes in ovule morphology that are induced because of the expression of the oncogene are discussed.

Asteraceae↗
PubMed2005

Negotiating responsibility: case studies of reproductive decision-making and prenatal genetic testing in families facing Huntington disease.

Three case studies are presented to further our understanding of how responsibility is negotiated in families when making decisions about genetic risk. These draw on a model of responsibility generated in a study of reproductive decision-making in families facing Huntington disease (HD) to illustrate the impact of prenatal testing on this process. This involves analyzing: how people present themselves as acting responsibly whether or not they utilize genetic testing; who they feel responsible to in their family and elsewhere; the impact that testing has on these relationships; and, how negotiating responsibility changes over time with repeated use of prenatal testing, changing risk status and maturational changes. Two key findings are: how decision-making is perceived can become as important as what is decided; and, how responsibility is negotiated depends on which of these relationships are prioritized. Implications of the findings for clinical practice are noted and suggestions made for further applications of the model.

Adult↗
PubMed1975

Clades versus clones in evolution: why we have sex.

Sexual reproduction predominates among organisms mainly because most evolutionary change is concentrated in speciation events, and asexual species cannot speciate in the normal sense. Asexual clones seldom diversify rapidly enough to overcome normal rates of extinction. In contrast, phylogenetic groups of sexual species (clades) commonly develop broad, heterogeneous adaptive zones rapidly enough to ensure survival.

Animals↗
PubMed1996

Oxytocin is required for nursing but is not essential for parturition or reproductive behavior.

Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential for mammalian reproduction. In addition to uterine contractions during labor and milk ejection during nursing, oxytocin has been implicated in anterior pituitary function, paracrine effects in the testis and ovary and the neural control of maternal and sexual behaviors. To determine the essential role(s) of oxytocin in mammalian reproductive function, mice deficient in oxytocin have been generated using embryonic stem cell technology. A deletion of exon 1 encoding the oxytocin peptide was generated in embryonic stem cells at a high frequency and was successfully transmitted in the germ line. Southern blot analysis of genomic DNA from homozygote offspring and in situ hybridization with an exonic probe 3' of the deletion failed to detect any oxytocin or neurophysin sequences, respectively, confirming that the mutation was a null mutation. Mice lacking oxytocin are both viable and fertile. Males do not have any reproductive behavioral or functional defects in the absence of oxytocin. Similarly, females lacking oxytocin have no obvious deficits in fertility or reproduction, including gestation and parturition. However, although oxytocin-deficient females demonstrate normal maternal behavior, all offspring die shortly after birth because of the dam's inability to nurse. Postpartum injections of oxytocin to the oxytocin deficient mothers restore milk ejection and rescue the offspring. Thus, despite the multiple reproductive activities that have been attributed to oxytocin, oxytocin plays an essential role only in milk ejection in the mouse.

Animals↗
PubMed2000

Insect juvenile hormone: from "status quo" to high society.

Juvenile hormone (JH) exerts pleiotropic functions during insect life cycles. The regulation of JH biosynthesis by neuropeptides and biogenic amines, as well as the transport of JH by specific binding proteins is now well understood. In contrast, comprehending its mode of action on target organs is still hampered by the difficulties in isolating specific receptors. In concert with ecdysteroids, JH orchestrates molting and metamorphosis, and its modulatory function in molting processes has gained it the attribute "status quo" hormone. Whereas the metamorphic role of JH appears to have been widely conserved, its role in reproduction has been subject to many modifications. In many species, JH stimulates vitellogenin synthesis and uptake. In mosquitoes, however, this function has been transferred to ecdysteroids, and JH primes the ecdysteroid response of developing follicles. As reproduction includes a variety of specific behaviors, including migration and diapause, JH has come to function as a master regulator in insect reproduction. The peak of pleiotropy was definitely reached in insects exhibiting facultative polymorphisms. In wing-dimorphic crickets, differential activation of JH esterase determines wing length. The evolution of sociality in Isoptera and Hymenoptera has also extensively relied on JH. In primitively social wasps and bumble bees, JH integrates dominance position with reproductive status. In highly social insects, such as the honey bee, JH has lost its gonadotropic role and now regulates division of labor in the worker caste. Its metamorphic role has been extensively explored in the morphological differentiation of queens and workers, and in the generation of worker polymorphism, such as observed in ants.

Animals↗
PubMed2002

The evolution of reproductive isolation in spatially structured populations.

Recent models of speciation have incorporated population structure and migration into the classic model of speciation in which reproductive isolation arises as a by-product of divergence. In this paper, we expanded these models to explore the joint effects of migration and population subdivision on speciation in a spatially explicit context. The results of our simulation support previous results concerning the influence of population subdivision on the accumulation of reproductive isolation. The simulation also shows that speciation in subdivided populations occurs most rapidly when subpopulations are not strictly allopatric. These results counter the widespread notion that speciation is most likely to occur in allopatric populations and suggest that there are useful insights to be gained by incorporating increasingly realistic types of population structure into models of speciation.

Biological Evolution↗
PubMed1986

The cost of sex in hermaphrodite populations with variation in functional sex.

In this paper an analysis is made of a model of selection for asexual reproduction in hermaphrodite (or monoecious) populations in which variation occurs in relative female and male fertilities. It is shown that the advantage of an asexual mutant (the cost of sex) increases with increasing degree of differentiation in functional sex. This effect is very marked at low levels of selfing, but weak with a high selfing rate. In general, the advantage of an asexual mutant in a hermaphrodite population depends on the relative resource allocation to male and female gametes, and increases with increasing bias to femaleness. Thus the cost of sex in gynodioecious populations is (with a low level of selfing) as high as in a dioecious population. This applies, however, to a nuclear genetic determination of gynodioecy, which is presumably rare. In a more realistic model assuming nuclear-cytoplasmic determination of gynodioecy the cost of sex is considerably lower.

Animals↗