Objective To determine the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on trophoblast invasiveness. Design Laboratory investigation. Setting Academic medical center. Patient(s) ...Placental tissues discarded after first-trimester terminations were obtained from patients with informed consent. Intervention(s) A cell line, HTR-8/SVneo, established from first-trimester cytotrophoblast, and villous explants, was treated with or without sildenafil, guanosine 3′,5′-cyclic monophosphate (cGMP) analog, cGMP inhibitor, or L-NAME (NG -nitro-L-arginine methyl ester hydrochloride) and cultured on fibronectin or Matrigel. Integrins α6β4 and α1β1 were detected by immunocytochemistry. Main Outcome Measure(s) Trophoblast outgrowth from villous tips, cytotrophoblast cell invasion, and integrin immunostaining were assessed in cytotrophoblast and explant cultures. Result(s) Integrin expression in trophoblast cells ex vivo switched from α6 to α1, and invasiveness increased, when exposed to sildenafil or cGMP agonist. Either cGMP antagonist or L-NAME blocked integrin switching and invasion induced by sildenafil. Elevation of nitric oxide pharmacologically induced invasion, but not when cGMP antagonist was present. Conclusion(s) Sildenafil altered trophoblast phenotype through a process dependent on nitric oxide availability and cGMP accumulation. In addition to its vasoactivity, sildenafil directly stimulates trophoblast extravillous differentiation, which would be favorable for implantation and reduce risk for adverse pregnancy outcomes.
Background: Numerous models show that if morphology and diet are correlated, frequency-dependent competition will lead to fitness differences among phenotypically dissimilar individuals within a ...species. Hypothesis: Selection acts primarily on diet, and only indirectly on morphology via its correlation with diet. Field sites and organism: British Columbia, Canada; 340 individual threespine stickleback (Gasterosteus aculeatus) from McNair Lake and 430 individuals from First Lake. Measurements: Stable isotopes ( delta super(13)C and delta super(15)N; a proxy for diet); trophic morphology (quantitative traits and geometric shape variables); and growth rates (RNA/DNA ratios; a proxy for the component of fitness arising from competitive or foraging ability). Analysis: Linear and quadratic regression of growth rate on stable isotopes and morphological variables to calculate the relationship between growth (a fitness proxy) and diet and/or morphology. When both morphology and isotopes affected growth rates, we used a path analysis to separate their effects. Conclusions: In the McNair Lake population, growth was dependent primarily on diet type and only indirectly on trophic morphology. In a second population, path analysis found that isotopes and body shape separately explain variation in growth rates. We infer that, in stickleback, selection on trophic morphology is often a correlated side-effect of selection on diet composition, rather than direct fitness effects of morphology per se.
Objective To examine the expression pattern of biomarker proteins in extravillous trophoblast (EVT) cells obtained noninvasively by trophoblast retrieval and isolation from the cervix (TRIC) in ...patients with early pregnancy loss compared with control patients with uncomplicated term delivery. Design Case-control study. Setting Academic medical center. Patient(s) Women with either early pregnancy loss (EPL, n = 10) or an uncomplicated term delivery (N = 10). Intervention(s) Endocervical specimens obtained from ongoing pregnancies at gestational ages of 5–10 weeks to generate an archive of EVT cells isolated by TRIC, with medical records examined to select specimens matched for gestational age at the time of endocervical sampling. Main Outcome Measure(s) Known serum biomarkers for adverse pregnancy outcome that are expressed by EVT cells were evaluated by semiquantitative immunocytochemistry, using antibodies against endoglin (ENG), FMS-like tyrosine kinase-1 (FLT-1), α-fetoprotein (AFP), pregnancy-associated plasma protein-A (PAPP-A), galectin-13 (LGALS13), galectin-14 (LGALS14), and placental growth factor (PGF). Result(s) The EVT purity was over 95% in all specimens, based on chorionic gonadotropin expression; however, the number of EVT cells obtained was significantly lower in women with EPL than the control group. There was a statistically significant elevation of AFP, ENG, and FLT-1, and statistically significant reduction of PAPP-A, LGALS14, and PGF in the EPL group compared with controls. Conclusion(s) In this pilot study, EVT cells isolated by TRIC early in gestation exhibited altered protein expression patterns before an EPL compared with uncomplicated term pregnancies.
Abstract
STUDY QUESTION
Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility?
SUMMARY ...ANSWER
MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples.
WHAT IS KNOWN ALREADY
Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility.
STUDY DESIGN, SIZE DURATION
MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells.
PARTICIPANTS/MATERIALS, SETTING METHODS
MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10–13), early-secretory (cycle days 14–19) or mid-secretory (cycle days 20–24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25–28) secretory phases.
MAIN RESULTS AND THE ROLE OF CHANCE
MSX1 transcript increased 5-fold (P < 0.05) between the late-proliferative and early secretory phase and was then down-regulated (P < 0.05) prior to receptivity for implantation. In fertile patients, MSX1 protein displayed strong nuclear localization in the luminal epithelium and glands, while it was weakly expressed in nuclei of the stroma. MSX1 protein levels accumulated throughout the secretory phase in all endometrial cellular compartments. MSX1 protein decreased (P < 0.05) in the glands between mid- and late-secretory phases. However, infertile patients demonstrated a broad reduction (P < 0.001) of MSX1 accumulation in all cell types throughout the secretory phase that was most pronounced (∼3-fold) in stroma and glands. Infertility was associated with persistent co-localization of E-cadherin and β-catenin in epithelial cell junctions in the mid- and late-secretory phases.
LIMITATIONS, REASONS FOR CAUTION
Details of the infertility diagnoses and other patient demographic data were not available. Therefore, patients with uterine abnormalities (Mullerian) could not be distinguished from other sources of infertility. Antibody against human MSX2 is not available, limiting the study to MSX1. However, both RNAs in the human endometrium are similarly regulated. In mice, Msx1 and Msx2 are imperative for murine embryo implantation, with Msx2 compensating for genetic ablation of Msx1 through its up-regulation in a knockout model.
WIDER IMPLICATIONS OF THE FINDINGS
This investigation establishes that the MSX1 homeobox protein accumulation is associated with the secretory phase in endometrium of fertile couples, and is widely disrupted in infertile patients. It is the first study to examine MSX1 protein localization in the human endometrium, and supported by genetic findings in mice, suggests that genes regulated by MSX1 are linked to the loss of epithelial cell polarity required for uterine receptivity during implantation.
STUDY FUNDING/COMPETING INTERESTS
This research was supported by the NICHD National Cooperative Reproductive Medicine Network grant HD039005 (M.P.D.), NIH grants HD068524 (S.K.D.), HD071408 (D.R.A., M.P.D.), and HL128628 (S.D.), the Intramural Research Program of the NICHD, March of Dimes (S.K.D., S.D.) and JSPS KAKENHI grant 26112506 (Y.H.). There were no conflicts or competing interests.
A recent study of the foraging gene in Drosophila illustrates a long-standing economic maxim that competition favors rare strategies. Two foraging alleles, rovers and sitters, each have higher ...fitness when rare — but only when competition is strong.
Question: Host races of phytophagous insects originate when a population adapts to a novel resource (host) while other populations remain resident on their ancestral host. The derived and ancestral ...host race populations will be subject to unequal selection intensity and genetic drift. Is this asymmetry responsible for asymmetric reproductive isolation observed in some populations? Hypothesis: Unequal intensity of selection and/or genetic drift between populations may lead to asymmetric reproductive isolation. Methods: We reared populations of Tribolium castaneum flour beetles on wheat or corn flour, which represent ancestral and suboptimal novel resources respectively. After approximately 43 generations, we assayed the fitness of wheat - and corn-evolved beetles on wheat and corn flour, and measured reciprocal pre-mating, pre-zygotic, and post-zygotic reproductive isolation between the ecotypes. Results: Three of our four corn-evolved populations went extinct. The one surviving corn population exhibited evidence of adaptation to corn half way through the experiment, but by the final generation we found little evidence of adaptation. Instead, the corn-evolved population had lower survival than the wheat-evolved population, independent of rearing environment. This result is consistent with maladaptation due to fixation of deleterious alleles via genetic drift. Pre-mating and post-zygotic reproductive isolation were both asymmetric, favouring the higher-fitness ancestral population. Females from both wheat-and corn-evolved populations avoided mating with corn-evolved males. This bias improved female fitness, because corn-evolved males had offspring with lower survival, regardless of female genotype or rearing medium. Conclusion: Strong selection in the derived (corn) population appears to have decreased population size to the extent that genetic drift led to the fixation of deleterious alleles that reduced corn-evolved male fitness. We posit that asymmetric pre-mating isolation arose because of this drift-induced maladaptation. Although our study is limited to a single pair of derived and ancestral populations, the results of our extensive pre-and post-mating reproductive isolation tests are consistent with this conclusion. This study highlights the importance of recognizing the fundamental entangling of drift and selection in the evolution of reproductive isolation, which complicates the frequently invoked dichotomy of selection and drift as distinct alternative forces in speciation.
The 32 species of the Centrarchidae are ecologically important components of the diverse fish communities that characterize North American freshwater ecosystems. In spite of a rich history of ...systematic investigations of centrarchid fishes there is extensive conflict among previous hypotheses that may be due to restricted taxon or character sampling. We present the first phylogenetic analysis of the Centrarchidae that combines DNA sequence data from both the mitochondrial and nuclear genomes and includes all described species. Gene sequence data were collected from a complete mtDNA protein coding gene (NADH subunit 2), a nuclear DNA intron (S7 ribosomal protein intron 1), and a portion of a nuclear DNA protein-coding region (
Tmo-4C4). Phylogenetic trees generated from analysis of the three-gene dataset were used to test alternative hypotheses of centrarchid relationships that were gathered from the literature. Four major centrarchid lineages are present in trees generated in maximum parsimony (MP) and Bayesian maximum likelihood analyses (BML). These lineages are
Acantharchus pomotis,
Micropterus,
Lepomis, and a clade containing
Ambloplites,
Archoplites,
Centrarchus,
Enneacanthus, and
Pomoxis. Phylogenetic trees resulting from MP and BML analyses are highly consistent but differ with regard to the placement of
A. pomotis. Significant phylogenetic incongruence between mtDNA and nuclear genes appears to result from different placement of
Micropterus treculi, and is not characteristic of relationships in all other parts of the centrarchid phylogeny. Slightly more than half of the 27 previously proposed hypotheses of centrarchid relationships were rejected based on the Shomodaira–Hasegawa test.
Many quantitative genetic and adaptive dynamic models suggest that disruptive selection can maintain genetic polymorphism and be the driving force causing evolutionary divergence. These models also ...suggest that disruptive selection arises from frequency-dependent intraspecific competition. For convenience or historical precedence, these models assume that carrying capacity and competition functions follow a Gaussian distribution. Here, we propose a new analytical framework that relaxes the assumption of Gaussian competition and carrying capacity functions, and investigate how alternative shapes affect the likelihood of disruptive selection. We found that the shape of both carrying capacity and competition kernels interact to determine the likelihood of disruptive selection. For certain regions of the parametric space disruptive selection is facilitated, whereas for others it becomes more difficult. Our results suggest that the relationship between the degree of frequency dependence and the likelihood of disruptive selection is more complex than previously thought, depending on how resources are distributed and competition interference takes place. It is now important to describe the empirical patterns of resource distribution and competition in nature as a way to determine the likelihood of disruptive selection in natural populations.
Multiple biological processes can generate sexual selection on male visual signals such as color. For example, females may prefer colorful males because those males are more readily detected ...(perceptual bias), or because male color conveys information about male quality and associated direct or indirect benefits to females. For example, male threespine stickleback often exhibit red throat coloration, which females prefer both because red is more visible in certain environments, and red color is correlated with male immune function and parasite load. However, not all light environments favor red nuptial coloration: more tannin-stained water tends to favor the evolution of a melanic male phenotype. Do such population differences in stickleback male color, driven by divergent light environments, lead to changes in the relationship between color and immunity? Here, we show that, within stickleback populations, multiple components of male color (brightness and hue of four body parts) are correlated with multiple immune variables (ROS production, phagocytosis rates, and lymphocyte:leukocyte ratios). Some of these color-immune associations persist across stickleback populations with very different male color patterns, whereas other color-immune associations are population-specific. Overall, lakes with red males exhibit stronger color-immune covariance while melanic male populations exhibit weak if any color-immune associations. Our finding that color-immunity relationships are labile implies that any evolution of male color traits (e.g., due to female perceptual bias in a given light environment), can alter the utility of color as an indicator of male quality.
Causes of maladaptation Brady, Steven P.; Bolnick, Daniel I.; Angert, Amy L. ...
Evolutionary applications,
August 2019, Letnik:
12, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Evolutionary biologists tend to approach the study of the natural world within a framework of adaptation, inspired perhaps by the power of natural selection to produce fitness advantages that drive ...population persistence and biological diversity. In contrast, evolution has rarely been studied through the lens of adaptation's complement, maladaptation. This contrast is surprising because maladaptation is a prevalent feature of evolution: population trait values are rarely distributed optimally; local populations often have lower fitness than imported ones; populations decline; and local and global extinctions are common. Yet we lack a general framework for understanding maladaptation; for instance in terms of distribution, severity, and dynamics. Similar uncertainties apply to the causes of maladaptation. We suggest that incorporating maladaptation‐based perspectives into evolutionary biology would facilitate better understanding of the natural world. Approaches within a maladaptation framework might be especially profitable in applied evolution contexts – where reductions in fitness are common. Toward advancing a more balanced study of evolution, here we present a conceptual framework describing causes of maladaptation. As the introductory article for a Special Feature on maladaptation, we also summarize the studies in this Issue, highlighting the causes of maladaptation in each study. We hope that our framework and the papers in this Special Issue will help catalyze the study of maladaptation in applied evolution, supporting greater understanding of evolutionary dynamics in our rapidly changing world.
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