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Leptin's actions on the reproductive axis: perspectives and mechanisms.

Energy availability influences reproductive fitness. The activity of the reproductive axis is sensitive to the adequacy of nutrition and the stores of metabolic reserves. The adipocyte-derived hormone leptin is postulated to reflect the state of nutrition and energy reserves and serve as a metabolic gate to the reproductive system. Genetically obese ob/ob mice (lacking endogenous leptin) are infertile, and treatment of these animals with exogenous leptin stimulates the activity of the reproductive endocrine system and induces fertility in both sexes. Severely food-restricted animals have reduced circulating levels of leptin, which are associated with markedly reduced secretion of the gonadotropins, LH, and FSH. Treatment of food-restricted mice, rats, sheep, and monkeys with exogenous leptin reverses the diet-induced inhibition of gonadotropin secretion. Leptin has also been suggested to have a role in timing the onset of puberty in several species, although evidence that leptin is the primary metabolic signal for initiating the onset of puberty in any species is controversial. Notwithstanding this debate, it is undisputed for all species studied to date that adequate levels of leptin in the circulation are essential (but not sufficient) for pubertal progression and that leptin treatment can reverse the delay in sexual maturation caused by food restriction. Double-label in situ hybridization studies in the brain of the mouse, rat, and monkey have revealed that hypothalamic neurons expressing proopiomelanocortin and neuropeptide Y coexpress the leptin receptor, whereas no evidence has been adduced that GnRH neurons express this receptor. Together, these observations suggest that leptin is a metabolic signal to the neuroendocrine reproductive system and that under conditions of inadequate energy reserves, low leptin levels act as a metabolic "gate" to inhibit the activity of the neuroendocrine reproductive axis in both sexes.

Aging↗

STE12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is part of protein-DNA complexes.

The STE12 gene of Saccharomyces cerevisiae is essential for the expression of genes required for mating, such as those involved in pheromone response, and for genes unrelated to mating but regulated by the presence of an adjacent copy of the transposable element Ty1. We show that the STE12 protein is a component of specific DNA-protein complexes that form with transcriptional control elements from Ty1 and the alpha-pheromone receptor gene STE2. Although a sequence involved in pheromone-dependent transcriptional activation is protected in both complexes, competition experiments indicate that the complexes are intrinsically different from each other. We show that another factor involved in cell-type-specific transcription, PRTF/GRM, is a component of the complex with the STE2 fragment but not the Ty1 fragment. We propose that the STE12 product interacts with different transcription factors in different sequence contexts and that PRTF/GRM is one of these factors.

Amino Acid Sequence↗

Heat shock protein 80 of Neurospora crassa: sequence analysis of the gene and expression during the asexual phase.

Heat shock protein 80 (Hsp80) of Neurospora crassa, a member of the stress-90 protein family, is a cytosolic molecular chaperone that interacts directly with Hsp70 to form a hetero-oligomeric complex. The complete nucleotide sequence of the gene encoding this protein, along with the 5'- and 3'-flanking DNA, is reported. The coding sequence is interrupted by two introns, 61 and 30 nucleotides, respectively, in length. The deduced amino acid sequence corresponds to a 695-residue polypeptide with a calculated molecular mass of 78,894 Da and an average pI of 4.94. Primer extension experiments demonstrated two transcription start sites, a major and a minor one. No sequence motifs resembling the standard eukaryotic heat shock elements were evident in the putative promoter region. Immunoblot analysis showed Hsp80 protein to be present in the mature, dormant conidia, while the hsp80 transcripts were not detected. Both the transcripts and the protein were present in the germinating conidia in the absence of externally applied stress.

Amino Acid Sequence↗

Genetic counseling for cancer patients and their families.

Cancer survivors who have undergone chemotherapy, radiotherapy, or surgery worry about the impact of treatment on their future health as well as on their reproductive ability. Genetic counseling--focusing on the probability of later cancers, possible infertility, and the chance of having children who are affected--is vital for cured cancer patients. Since each type of cancer and each type of treatment has unique sequelae, genetic counselors must make a thorough review of the patient's environmental and family history. They must also be alert for cancer family syndromes, including cancers of the breast, ovary, and colon.

Family↗

Sexual reproduction plays a major role in the genetic structure of populations of the fungus Mycosphaerella graminicola.

The relative contributions of sexual and asexual reproduction to the genetic structure of populations can be difficult to determine for fungi that use a mixture of both types of propagation. Nuclear RFLPs and DNA fingerprints were used to make indirect and direct measures of departures from random mating in a population of the plant pathogenic fungus Mycosphaerella graminicola during the course of an epidemic cycle. DNA fingerprints resolved 617 different genotypes among 673 isolates sampled from a single field over a 3-month period. Only 7% of the isolates represented asexual clones that were found more than once in the sample. The most common clone was found four times. Genotypic diversity averaged 85% of its maximum possible value during the course of the epidemic. Analyses of multilocus structure showed that allelic distributions among RFLP loci were independent. Pairwise comparisons between individual RFLP loci showed that the majority of alleles at these loci were in gametic equilibrium. Though this fungus has the capacity for a significant level of asexual reproduction, each analysis suggested that M. graminicola populations maintain a genetic structure more consistent with random-mating over the course of an epidemic cycle.

Ascomycota↗

[Genetic structure of species community of macromycetes of the genus Leccinum Gray (Basidiomycetes, Boletaceae) of the right-bank Poles'ye].

The biochemical gene marking of the macromycete community of the genus Leccinum revealed nine reproductively isolated genetically differentiated forms instead of 2-5 forms traditionally recognized in Poles'ye. From 20 to 85% of the loci studied were found to have genetic distinctions and the degree of genetic variation did not always correlate with the morphological features of the forms identified. The variation of the locus number was found to be an important differentiating factor characteristic for this genus. In the group of L. scabrum s. I., every second locus was duplicated, whereas multiple isozymes were absent in L. aurantiacum s. I. The extremely high level of allozyme variation in macromycetes was found. The equilibrium between the expected and observed genotypes in the fruit body samples was established and discussed. It was the evidence of the fact that a panmictic model can be applied to the mushrooms of this genus, and that each fruit body is an individual organism.

Basidiomycota↗

Fitness of indirectly transmitted pathogens: restraint and constraint.

Many pathogens of medical and veterinary importance have obligatory multihost life cycles. Yet, theoretical models aiming to predict patterns of pathogen reproductive success and the limited empirical data available with which to evaluate them, focus on directly transmitted microparasites. Patterns of host exploitation and the relative fitness of individual pathogen genotypes throughout the different host stages of multihost life cycles have thus remained ignored. We examined correlated responses to artificial selection of Schistosoma mansoni lines selected for high or low infection intensity in the intermediate host. Pathogen fitness in the intermediate host was strongly inversely correlated with pathogen fitness in the definitive host. Moreover, high pathogen infection intensity was associated with decreased, rather than increased, virulence to its intermediate host. These results raise important implications regarding the impact of genetic constraints on the maintenance of genetic and phenotypic polymorphisms in natural populations, the evolution and coevolution of parasite virulence and host specialization, as well as the success of host-directed control programs.

Animals↗

Genetic variation and gene flow of broadcast spawning and planula brooding coral, Goniastrea aspera (Scleractinia) in the Ryukyu Archipelago, southern Japan.

The scleractinian coral Goniastrea aspera (Verrill) undergoes both broadcast spawning and planulae brooding in the Ryukyu Archipelago of southern Japan. Genetic variation and gene flow in G. aspera were studied using allozyme electrophoresis. We tested the hypothesis that gene flow is determined by the competency period of the planulae. We also assessed the relative contributions of sexual and asexual reproduction to recruitment. For the five staining systems surveyed, G. aspera encoded five polymorphic loci and one monomorphic locus. The genotype frequencies in each population significantly differed from the expected Hardy-Weinberg equilibrium (HWE), indicating that the local populations of G. aspera are not fully panmictic. The high ratio of the observed number of genotypes to the number of individuals (0.90 +/- 0.07, mean NG:N +/- SD) and the observed to expected genotypic diversity (0.84 +/- 0.11, mean GO:GE +/- SD) suggested that each population is likely maintained by sexual reproduction. The genetic differentiation (FST) and value of average number of migrants per generation (Nem) among and within regions ranged from 0.025 to 0.104 and 2.2 to 9.6, respectively. Comparisons with other species demonstrated that larva survival rates also influence gene flow. In addition, gene flow on distant reefs by planulae originating from spawning might prevent divergence by planulae originating from brooding for short-distant dispersal among and within populations of G. aspera in the Ryukyu Archipelago.

Animals↗

Genetic analysis of two distinct reproductive strategies in sexual and asexual field populations of an endoparasitic wasp, Venturia canescens.

Asexual (thelytokous) females of the parasitoid Venturia canescens, which develop inside another insect, exhibit evolutionarily stable mixtures of life-history strategies, allowing two genetically distinct wasp lines to coexist sympatrically on the same host resources. Since the two asexual lines differ in a virus-like particle protein-coding gene (VLP1), the question is whether the VLP1 gene is genetically associated with the phenotype. The recent isolation of facultative sexual (arrhenotokous) and asexual V. canescens strains from the same location in Southern France has enabled an investigation of the genetic basis for the observed phenotypic differences, by comparing the two asexual lines with the corresponding homozygous VLP1 genotypes in arrhenotokous strains. This analysis showed similar patterns of morphological and functional differences exist in the ovaries of the two asexual VLP1 lines and in the two homozygous VLP1 genotypes from the field, suggesting that the VLP1 gene alteration either causes the ovarian phenotype or is genetically closely linked to the putative gene. However, the VLP1-gene may not be the only gene contributing to the phenotypic effects observed in the asexual lines. Although the two VLP1-alleles segregate with the relative differences in the ovary distribution of eggs, the absolute egg numbers differ in the corresponding asexual and sexual genotypes. This suggests that an additional unlinked gene may be involved in the transfer of eggs from the ovarioles into the oviduct.

Animals↗

Detection of genetically divergent clone mates in apomictic dandelions.

This study aims to identify genetically diverged clone mates in apomictic dandelions. Clone mates are defined as individuals that may have diverged as a result of mutation accumulation and that have undergone only clonal reproduction since their most recent common ancestor. Based on distinctive morphology and an aberrant and rare chloroplast haplotype, northwest European individuals of Taraxacum section Naevosa are well suited for the detection of clonal lineages in which mutation has occurred. In the case of strictly clonal reproduction, nuclear genetic variability was expected to be hierarchically organized. Nucleotide polymorphisms in internal transcribed spacer (ITS) sequences, however, were incompatible with a clonal structure of the Norwegian individuals, probably due to persistent ancestral polymorphisms that pre-date the origin of the Naevosa clone. This interpretation is supported by the presence of ITS variants in section Naevosa that were also found in distantly related dandelions. In contrast to the ITS sequence data, amplified fragment length polymorphisms (AFLPs), isozymes and microsatellites strongly supported the contention of prolonged clonal reproduction and mutation accumulation in Norwegian Naevosa. Because these markers are generally considered to be more variable and more rapidly evolving than ITS sequences, mutations in these markers probably evolved after the origin of the clone. Within the Norwegian clone, a surprising number of markers distinguished the clone mates. As a consequence, incorporation of mutation in the detection of clone mates is anticipated to have a big impact on estimates of size, geographical range and age of clones as well as on experimental designs of studies of clonal plants.

Asteraceae↗

Just ignore it? Parents and genetic information.

This paper discusses whether prospective parents ought to find out about their genetic constitution for reproductive reasons. It is argued that ignoring genetic information can be in line with responsible parenthood or perhaps even recommendable. This is because parenthood is essentially an unconditional project in which parents ought to commit themselves to nurturing any kind of child. Besides, the traditional reasons offered for the unfortunateness of impairments and the tragic fate of families with disabled children are not convincing. Other morally problematic outcomes of genetics, such as discrimination against individuals with impairments, and limiting free parental decision making, are also considered.

Child↗

Multicolor FISH analysis of chromosomal breaks, duplications, deletions, and numerical abnormalities in the sperm of healthy men.

Transmitted de novo structural chromosomal abnormalities, the majority of which are paternally derived, can lead to abnormal reproductive outcomes as well as genetic diseases in offspring. We developed and validated a new multicolor FISH procedure (sperm ACM, which utilizes DNA probes specific for the alpha [1cen], classical, [1q12], and midi [1p36.3] satellites of chromosome 1) which utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical abnormalities plus two categories of structural aberrations: (1) duplications and deletions of 1pter and 1cen, and (2) chromosomal breaks within the 1cen-1q12 region. In healthy men, the average frequencies of sperm with duplications and deletions were (a) 4.5 +/- 0.5 and 4.1 +/- 1.3 per 10(4) involving 1pter and (b) 0.9 +/- 0.4 and 0.8 +/- 0.3 per 10(4) involving 1cen, respectively. The frequency of sperm exhibiting breaks within the 1cen-1q12 region was 14.1 +/- 1.2 per 10(4). Structural aberrations accounted for 71% of the abnormalities detected by sperm ACM, which was significantly higher than numerical abnormalities (P=2x10-8). Our findings also suggest that, for healthy men, (a) sperm carrying postmeiotic chromosomal breaks appear to be more prevalent than those carrying products of premeiotic or meiotic breakage or rearrangements, (b) the high frequency of chromosome breaks measured after "fertilization" by the hamster-egg cytogenetic method already appear to be present and detectable within human sperm by FISH, and (c) there are nonrandom and donor-specific distributions of breakpoint locations within 1q12 in sperm. FISH facilitates the analysis of much larger numbers of sperm than was possible when the hamster-egg method was used. Therefore, FISH-based procedures for simultaneously detecting chromosomal breaks, rearrangements, and numerical abnormalities in sperm may have widespread applications in human genetics, genetic toxicology, and reproductive medicine.

Animals↗

Reproductive performance and variation in body weight during annual cycles for crossbred beef cows with different genetic potential for milk.

Reproductive performance and body weights were studied in 81, 79 and 88 spring-calving beef cows from three groups, reasonably similar in growth rate and mature size but different in level of milk production (low [L] = Hereford x Angus, medium [M] = Red Poll x Angus and high [H] = Milking Shorthorn x Angus). Milk group did not have a significant effect on dates of first postpartum estrus and first and last breeding or in the intervals from calving to first estrus, to first breeding and to last breeding. A significant age-of-cow x milk-group interaction was found for pregnancy rate (PR, P less than .10) and calf-crop percentage (CC, P less than .05). In heifers, PR and CC were lowest for the L (85.6 and 73.6%) and highest for the M group (94.2 and 92.5%); in 2-yr-olds there were no differences, and in older cows, PR was highest for the L (94.8%) and lowest for the H group (91.6%), and there were no differences in CC. As estimated from Brody's growth curves, mature sizes were 530 +/- 5.7, 471 +/- 4.6 and 499 +/- 4.2 kg for the L, M and H groups, respectively. Of weights taken on four occasions during the year, October weight was the highest for all cows. February weight, minus the estimated gravid uterus weight, was the lowest for L and M cows, and May weight was lowest for H cows. Weight fluctuation over an annual cycle was greatest for the L group. Under these experimental conditions, cows in all groups were able to consume sufficient energy and gain or lose body reserves to achieve similar reproductive performance while differing in lactation performance.

Animals↗

Polymorphism and reproductive mode in the rotifer, Asplanchna sieboldi: relationship between meiotic oogenesis and shape of body-wall outgrowths.

Sexuality and polymorphism are closely coupled in the rotifer Asplanchna sieboldi. In a graded response to dietary tocopherol, embryos develop body-wall outgrowths of various sizes and shapes. Also in a graded response to this compound, some of the affected females produce eggs undergoing meiotic instead of mitotic oogenesis. The haploid eggs of such mictic females develop parthenogenetically into males instead of females. The incidence of mictic females among animals with different shapes was studied among cohorts from mothers subjected to different inducing conditions. The hypothesis that external tocopherol concentrations absolutely fix the probability of meiotic oogenesis was rejected. The other extreme hypothesis, that the probability of meiotic oogenesis is fixed by morphotype, was rejected for animals at the low end of the morphotypic scale but accepted for the more strongly-affected individuals. The probability of meiotic oogenesis is thus constant for the higher morphotypes. The ascertainment of morphotype frequencies in natural or laboratory populations may suffice for estimating the incidence of sexual forms; furthermore studies of factors affecting the body-wall-outgrowth response may also bear directly upon regulation of sexual reproduction in this species.

Animals↗