Intrinsic Correlation between the Fraction of Liquidlike Zones and the ß Relaxation in High-Entropy Metallic Glasses.

Lacking the structural information of crystalline solids, the origin of the relaxation dynamics of metallic glasses is unclear. Here, we report the evolution of stress relaxation of high-entropy metallic glasses with distinct ß relaxation behavior. The fraction of liquidlike zones, determined at each temperature by the intensity of stress decay, is shown to be directly related to both the aging process and the spectrum of relaxation modes obtained by mechanical spectroscopy. The results shed light on the intrinsic correlation between the static and dynamic mechanical response in high-entropy and conventional metallic glasses, pointing toward a sluggish diffusion high-entropy effect in the liquid dynamics.

Erratum: Intrinsic Correlation between the Fraction of Liquidlike Zones and the ß Relaxation in High-Entropy Metallic Glasses [Phys. Rev. Lett. 129, 175501 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.175501.

Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

BACKGROUND: Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. RESULTS: Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel n2) to the initiation of puberty. CONCLUSIONS: This study has - for the first time - linked testis maturation to specific miRNAs and their inversely correlated expressed targets in Atlantic salmon. The study indicates a broad functional conservation of already known miRNAs and associated pathways involved in the transition into puberty in vertebrates. The analysis also reveals miRNAs not previously associated with testis tissue or its maturation, which calls for further functional studies in the testis.

INSL3 stimulates spermatogonial differentiation in testis of adult zebrafish (Danio rerio).

INSL3 (insulin-like peptide 3) is a relaxin peptide family member expressed by Leydig cells in the vertebrate testis. In mammals, INSL3 mediates testicular descent during embryogenesis but information on its function in adults is limited. In fish, the testes remain in the body cavity, although the insl3 gene is still expressed, suggesting yet undiscovered, evolutionary older functions. Anti-Müllerian hormone (Amh), in addition to inhibiting spermatogonial differentiation and androgen release, inhibits the Fsh (follicle-stimulating hormone)-induced increase in insl3 transcript levels in zebrafish testis. Therefore, the two growth factors might have antagonistic effects. We examine human INSL3 (hINSL3) effects on zebrafish germ cell proliferation/differentiation and androgen release by using a testis tissue culture system. hINSL3 increases the proliferation of type A undifferentiated (Aund) but not of type A differentiating (Adiff) spermatogonia, while reducing the proliferation of Sertoli cells associated with proliferating Aund. Since the area occupied by Aund decreases and that of Adiff increases, we conclude that hINSL3 recruits Aund into differentiation; this is supported by the hINSL3-induced down-regulation of nanos2 transcript levels, a marker of single Aund spermatogonia in zebrafish and other vertebrates. Pulse-chase experiments with a mitosis marker also indicate that hINSL3 promotes spermatogonial differentiation. However, hINSL3 does not modulate basal or Fsh-stimulated androgen release or growth factor transcript levels, including those of amh. Thus, hINSL3 seems to recruit Aund spermatogonia into differentiation, potentially mediating an Fsh effect on spermatogenesis.

[Translated article] Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis.

OBJECTIVE: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. MATERIAL AND METHOD: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses -PRISMA- standards, and the inclusion criteria following the PICO strategy. Data from included studies were analysed using Review Manager 5.4 software. RESULTS: A total of seven retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group versus 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). CONCLUSION: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.

Return to full duty after anterior cruciate ligament reconstruction surgery in military personnel: A meta-analysis. / Retorno a la actividad completa tras cirugía de reconstrucción de ligamento cruzado anterior en personal militar: metaanálisis.

OBJECTIVE: A meta-analysis was carried out to evaluate the clinical-functional results of anterior cruciate ligament surgery in military population, as well as the complications associated with it. MATERIAL AND METHOD: Three major database sources up to December 2022 (PubMed, Google Scholar, and ScienceDirect) were searched for outcomes after anterior cruciate ligament surgery in military personnel. The systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses -PRISMA- standards, and the inclusion criteria following the PICO strategy. Data from included studies were analyzed using Review Manager 5.4 software. RESULTS: A total of 7 retrospective studies were selected. The general rate of return to full duty in military personnel was 62.3% (61.5% for the non-officer group vs. 68.3% for the officer group) without this difference being significant (p=0.92). The general rate of meniscal injury in the military was 58.8%, without this difference being significant (p=0.88). The homogeneity in both cases was good (I2=0%, p=0.99). CONCLUSION: Return to full military duty can be used in the military population as a marker of success after anterior cruciate ligament reconstruction. It should be noted that a large number of military personnel experience permanent activity limitations that prevent full return to service.

Non-pharmacological interventions to reduce physical restraints in critical care units.

Physical restraint use in critical care units is a frequent low-value care practice influenced by numerous factors creating a local culture. The translation of evidence-based recommendations into clinical practice is scarce so, the analysis of interventions to de-adopt this practice is needed. This update aims to describe and identify nonpharmacological interventions that contribute to minimising the use of physical restraints in adult critically ill patients. Interventions are classified into two groups: those that include education alone and those that combine training with one or more components (multicomponent interventions). These components include less restrictive restraint alternatives, use of physical and cognitive stimulation, decision support tools, institutional multidisciplinary committees, and team involvement. The heterogeneity in the design of the programmes and the low quality of the evidence of the interventions do not allow us to establish recommendations on their effectiveness. However, multicomponent interventions including training, physical and cognitive stimulation of the patient and a culture change of professionals and the organisations towards making restraints visible might be the most effective. The implementation of these programmes should underpin on a prior analysis of each local context to design the most effective-tailored combination of interventions to help reduce or eliminate them from clinical practice.

Appropriateness of behavioural scales in the monitoring of pain in the critically ill patient unable to self-report.

Appropriateness is a dimension of quality that evaluates the effective use of technologies, resources or interventions in specific situations or populations, assessing whether our interventions do more benefit than harm. The evidence regarding pain monitoring in the critically ill patient points to the periodic assessment of pain using appropriate tools, with the aim of improving pain management and more efficient use of analgesics in the intensive care unit. The first step would be to assess the patient's ability to communicate or self-report and, based on this, to select the most appropriate pain assessment tool. In patients who are unable to self-report, behavioural pain assessment tools are recommended. When we talk about the suitability of behavioural scales for pain monitoring in critically ill patients unable to self-report, we refer to their use with a clear clinical benefit, i.e. using the right tool for pain assessment to be effective, efficient and consistent with bioethical principles. To our knowledge, there are no published data on the suitability of pain assessment tools in unable to self-report critically ill patients, so, in the framework of continuous quality improvement in pain care, new research should incorporate this approach by integrating the best scientific evidence with current clinical practice.

Stability in air of silver and silver oxide nanoparticle shells deposited over silica spheres without using coupling agents.

The deposition of silver nanoparticles on the surface of silica was carried out using our simple, robust and rapid chemical method without surface modification of silica or added coupling agents. The process was carried out at room temperature using water/methanol mixtures, tetraethyl orthosilicate as Si source and silver nanoparticles (NPs) in a single-pot reaction. Using EDS, XRD, HRTEM and High Angle Annular Dark Field (HAADF) STEM characterization techniques, we have found the coexistence of silver NPs and silver oxides NPs anchored to the surface of sub-micron silica spheres, with Ag NPs predominating sizes around 2-3 nm approximately, and Ag2O NPs sizes over 10 nm.

Communication: are metallic glasses different from other glasses? A closer look at their high frequency dynamics.

Using high resolution inelastic x-ray scattering we studied the collective dynamics of the Pd(77)Si(16.5)Cu(6.5) metallic glass, focusing on the energy-momentum region where the boson peak appears. The dispersion relation and the width of the acoustic excitations are determined showing how the longitudinal acoustic modes maintain their dispersive character for frequencies well above the boson peak frequencies. Moreover, we prove that close to these frequencies there is a softening of the apparent sound speed indicating a failure of the Debye continuum approximation at the boson peak frequencies and challenging previous results on other metallic glasses.

Influence of oceanic and climate conditions on the early life history of European seabass Dicentrarchus labrax.

Understanding how marine fish early-life history is affected in the long-term by environmental and oceanographic factors is fundamental given its importance to population dynamics and connectivity. This work aimed at determining the influence of these processes on the interannual variability in hatch day and early-life growth patterns of European seabass, over a seven-year period (2011-2017) in the Atlantic Iberian coast. To accomplish this, otolith microstructure analysis was used to determine seabass hatch day and to develop early-growth correlations. In most years, hatching occurred from February to April, with two exceptions: in 2012, hatching started in early-January, and in 2016 an exceptionally long hatching period was registered. Using generalized additive models (GAM), we observed that sea surface temperature (SST), the North Atlantic Oscillation index (NAOi) and Chlorophyll-a (Chla) were the main drivers behind the inter-annual variability in seabass hatch day. Analysis of correlations between growth increments allowed assessing important periods of seabass growth and how future growth is affected. Since seawater temperature is among the main drivers for seabass recruitment and growth, its life cycle may be hampered due to ocean warming and an increasingly unstable climate, with consequences for the natural marine stocks and their harvest.

The role of dopamine receptors in lymphocytes and their changes in schizophrenia.

Dopamine and its 5 receptors, which are grouped into two families (D1-like and D2-like), modulate functions at a systemic level in both the central nervous system and periphery. The central nervous system and the immune system are the main adaptive systems, which participate in a continuous and functional crosstalk to guarantee homeostasis. On binding to its 5 dopamine receptors, dopamine acts as a co-regulator of the immune system, contributing to the interaction of the central nervous system and inflammatory events and as a source of communication between the different immune cells. Dopaminergic perturbations in the central nervous system are observed in several neurological and psychiatric disorders. Schizophrenia is one of the most common mental disorders with a poorly understood pathoaetiology that includes genetic and environmental components that promote alterations in the dopaminergic system. Interestingly, abnormalities in dopamine receptors expression in lymphocytes of schizophrenia patients have been reported, often significantly correlating with the severity of the psychotic illness. Here, we review the current literature regarding the dopaminergic system in human lymphocytes and its alterations in schizophrenia.

Spatiotemporal Oscillatory Patterns During Working Memory Maintenance in Mild Cognitive Impairment and Subjective Cognitive Decline.

Working memory (WM) is a crucial cognitive process and its disruption is among the earliest symptoms of Alzheimer's disease. While alterations of the neuronal processes underlying WM have been evidenced in mild cognitive impairment (MCI), scarce literature is available in subjective cognitive decline (SCD). We used magnetoencephalography during a WM task performed by MCI (n = 45), SCD (n = 49) and healthy elders (n = 49) to examine group differences during the maintenance period (0-4000ms). Data were analyzed using time-frequency analysis and significant oscillatory differences were localized at the source level. Our results indicated significant differences between groups, mainly during the early maintenance (250-1250ms) in the theta, alpha and beta bands and in the late maintenance (2750-3750ms) in the theta band. MCI showed lower local synchronization in fronto-temporal cortical regions in the early theta-alpha window relative to controls (p = 2 × 10-03) and SCD (p = 4 × 10-03), and in the late theta window relative to controls (p = 1 × 1003) and SCD (p = 0.01). Early theta-alpha power was significantly correlated with memory scores (rho = 0.24,p = 0.02) and late theta power was correlated with task performance (rho = 0.24,p = 0.03) and functional activity scores (rho = -0.23,p = 0.02). In the early beta window, MCI showed reduced power in temporo-posterior regions relative to controls (p = 3 × 10-03) and SCD (p = 0.02). Our results may suggest that these alterations would reflect that memory-related networks are damaged.

Realistic scenarios of environmental disturbance lead to functionally important changes in benthic species-environment interactions.

Changes in community structure concurrent with environmental forcing often form a precursor to changes in species diversity, and can have substantive consequences for ecosystem functioning. Here, we assess the effects of altered levels of evenness that are representative of different levels of eutrophication and changes in salinity associated with altered precipitation patterns, on the mediation of nutrient release by sediment-dwelling invertebrate communities. We find that an adjustment towards a more even distribution of species corresponds with an increase in sediment particle reworking that, in general, translates to increased levels of nutrient release. This response, however, is dependent on the functional role of each species in the community and is influenced by concomitant changes in salinity, especially when salinity extends beyond the range typically experienced by the community. Overall, our findings highlight the dynamic nature of species contributions to functioning and reinforce the importance of understanding when, and how, the mechanistic basis of species-environment interactions are modified as the influence of abiotic and biotic factors flex under periods of directional forcing.

Improving the lipid nutritive value of poultry meat through the incorporation of a dehydrated leguminous-based forage in the diet for broiler chicks.

Dehydrated forages are assumed to be good sources of alpha-linolenic acid (ALA) and lipid-soluble antioxidant compounds (vitamin E homologs and beta-carotene). The effects of including a dehydrated leguminous-based forage in a typical diet for broiler chicken, on performance, meat quality, and fatty acid composition were evaluated. One hundred sixty 1-d-old male commercial broiler chicks (Ross 308) were housed in 20 battery brooders. During the 28-d growth period, the animals were fed ad libitum with a typical maize-soybean high-energy feed having access or not to a dehydrated leguminous-based forage provided in a separate feeder. The results revealed that dehydrated forage intake (which was 11.1% of the total intake) had no impact in broiler performance (P > 0.05). The capacity of ingested forage to modulate broiler meat fatty acid profile and the meat content in total cholesterol, tocopherols, tocotrienols, and beta-carotene was investigated in broiler chicks slaughtered at d 28. Dehydrated forage consumption had no effect on the lipid-soluble antioxidant compounds and cholesterol contents of broiler meat but had a significant effect on meat fatty acid profile. Although forage intake did not affect the linoleic acid and ALA contents in poultry meat, the levels of n-3 long-chain polyunsaturated fatty acids [eicosapentaenoic (P = 0.004), docosapentaenoic (P = 0.010), and docosahexaenoic (P = 0.007)] in breast meat were significantly higher in animals consuming leguminous biomass, which suggest a higher conversion of ALA into its derivatives in these birds. Overall, the data confirms that incorporation of a dehydrated leguminous-based forage in the diet for broiler chicks results in more favorable polyunsaturated fatty acids/saturated fatty acids and n-6/n-3 nutritional ratios for animals slaughtered at earlier stages of grow.

Pasture intake improves the performance and meat sensory attributes of free-range broilers.

Free-range chickens are assumed to consume low to moderate levels of pasture, although the effects of forage intake in broiler performance and poultry meat quality remain to be established. In addition, despite cellulases and hemicellulases being widely used as feed supplements to improve the nutritive value of cereal-based diets for fast-growing broilers, the potential interest of these biocatalysts in the production of free-range chicken is yet to be established. In this study, broilers of the RedBro Cou Nu x RedBro M genotype were fed a cereal-based diet in portable floorless pens located either on a rainfed subterranean clover (Trifolium subterraneum) pasture or on an irrigated white clover (Trifolium repens) pasture. Control birds were maintained at the same site in identical pens but with no access to pastures. The importance of pasture intake and enzyme supplementation in the performance and meat sensory properties of the free-range chicken from d 28 to 56 was investigated. The results revealed that although cellulase and hemicellulase supplementation had no impact on broiler performance (P > 0.05), birds foraging on legume-based pastures reached significantly greater final BW. The data suggest that the improvement in broiler performance results from increased intake of the cereal-based feed rather than from an improvement in the efficiency of nutrient utilization per se. Interestingly, although the intake of the subterranean clover pasture had no impact on the tenderness, juiciness, and flavor of broiler meat, members of a 30-person consumer panel classified the meat from grazing broilers with greater scores for overall appreciation. Together, the results suggest that pasture intake promotes bird performance while contributing to the production of broiler meat with preferred sensory attributes.

Restricting the intake of a cereal-based feed in free-range-pastured poultry: effects on performance and meat quality.

Pastures are assumed to be good sources of alpha-linolenic acid (ALA) and other bioactive compounds. In this study, we evaluated the effects of restricting the intake of a cereal-based feed on the consumption of a legume-based pasture, and consequently on poultry performance and meat quality. Broilers of the RedBro Cou Nu x RedBro M genotype were fed a cereal-based feed at different intake restriction levels (100, 75, or 50% of ad libitum intake) in portable floorless pens located on a subterranean clover (Trifolium subterraneum) pasture. Control birds were maintained at the same site in identical pens but had no access to pasture. The results revealed that, although the growth rate achieved was below the levels expected for the genotype, restriction of cereal-based feed intake had a significant impact on broiler weight gain and feed conversion while leading to an increase in relative leguminous pasture intake (from 1.6 to 4.9% of the total intake, on a DM basis). In addition, bird performance was positively influenced by pasture consumption. The capacity of ingested pasture to modulate carcass characteristics, broiler meat fatty acid profiles, and the meat content of total cholesterol, tocopherols, and to-cotrienols was investigated in broiler chickens slaughtered on d 64. Pasture intake decreased carcass yield (P < 0.05) and meat pH (P < 0.001) and improved breast skin pigmentation (P < 0.001). Consumption of the leguminous pasture had a marginal effect in the vitamin E profiles and cholesterol contents of broiler meat (P < 0.05), although it significantly affected the meat fatty acid profile. Although pasture intake did not influence the linoleic acid content of poultry meat, the levels of n-3 polyunsaturated fatty acids in breast meat [ALA (P < 0.001), eicosapentaenoic acid (P < 0.001), docosapentaenoic acid (P < 0.001), and docosahexaenoic acid (P < 0.001)] were significantly greater in birds consuming the leguminous biomass. Overall, the data suggest an important deposition of ALA and some conversion of ALA to its derivatives in pastured broilers subjected to a restriction of cereal-based feed.

Crop beta-glucanase activity limits the effectiveness of a recombinant cellulase used to supplement a barley-based feed for free-range broilers.

1. The supplementation of diets rich in soluble polysaccharides with microbial cellulases and hemicellulases decreases digesta viscosity and promotes broiler performance. 2. In contrast, recent experiments suggest that polysaccharidases are ineffective for improving the nutritive value of pasture biomass used by free-range broilers. However, the feasibility of using cellulases and hemicellulases to improve the utilisation of cereal-based feeds by pastured poultry remains to be established. 3. A study was undertaken to investigate the capacity of a recombinant cellulase from Clostridium thermocellum to improve the nutritive value of a barley-based feed for free-range pastured broilers of the RedBro Cou Nu x RedBro M genotype. 4. The results show that supplementation of a barley-based diet with a recombinant beta-glucanase had no effect on the performance of free-range broilers, foraging in legume-based diets from d 28 to 56. In addition, the results confirm that the lack of effect of the recombinant enzyme in improving the nutritive value of the barley-based feed does not result from enzyme proteolysis or inhibition in the gastrointestinal tract. 5. Significantly, beta-glucanase activity was identified in the crop of non-supplemented animals. The data suggest that endogenous cellulases originated both from the barley-based feed and from the crop microflora. 6. The results presented here suggest that in older birds of slow-growing genotypes associated with free-range production systems, previously unknown sources of beta-glucanases, such as the feed and microbial symbiotic microflora, can affect the effectiveness of exogenous enzymes added to the feed.

Does Body Mass Index Influence the Physiological and Perceptual Demands Associated with Defensive Tactics Training in State Patrol Officers?

The purpose of this investigation was to determine the physiological and perceptual demands associated with defensive tactics (DEFTAC) training among state patrol officers of different BMI (body mass index) categories. Twenty-four male state patrol officers (n = 24, age 36.00 + 7.86 yrs) voluntarily agreed to participate in data collection during a DEFTAC gauntlet. Anthropometric information (height (HT) 182.19 + 7.43 cm and weight (WT) 96.31 + 17.45 kg), body mass index (BMI), peak and average heart rates, duty weight, BLa, and RPE, were recorded. Officers were then divided into two-groups (Healthy BMI (BMI ≤ 25), n = 12, Overweight (BMI ≥ 25), n = 12). Analyses of covariance (ANCOVAs) were conducted to determine the effect of BMI on the outcome variables. Furthermore, a Pearson's product-moment correlation coefficient was also conducted to determine if significant relationships between RPE, BLa, and HR existed between groups. Significant mean score differences between healthy and overweight officers were found in measures of age [t(22) 4.12, p< 0.01, R2 = .44], and weight of duty gear [t(21) 3.96, p<0.01, R2 = .33]. When used as a covariate, age also predicted average HR% [ F(1, 21) = 6.19, p < .05, partial η2 = .24]. Significant relationships were found in the healthy group between RPE and DEFTAC time, DEFTAC time and score, as well as score and post BLa. Significant relationships for the overweight group between peak (HR) percentage and post BLa, peak (HR) percentage and RPE, DEFTAC time and duty weight, and between weight and DEFTAC time. The results of this study suggest that overweight officers may have lower DEFTAC scores when compared to their healthy counterparts. Based on the results, it seems reasonable to compare physiological variables from this population to those from combative sports as well as for officers to achieve and maintain a healthy BMI value in order to improve individual DEFTAC performance.

Antagonistic regulation of spermatogonial differentiation in zebrafish (Danio rerio) by Igf3 and Amh.

Fsh-mediated regulation of zebrafish spermatogenesis includes modulating the expression of testicular growth factors. Here, we study if and how two Sertoli cell-derived Fsh-responsive growth factors, anti-Müllerian hormone (Amh; inhibiting steroidogenesis and germ cell differentiation) and insulin-like growth factor 3 (Igf3; stimulating germ cell differentiation), cooperate in regulating spermatogonial development. In dose response and time course experiments with primary testis tissue cultures, Fsh up-regulated igf3 transcript levels and down-regulated amh transcript levels; igf3 transcript levels were more rapidly up-regulated and responded to lower Fsh concentrations than were required to decrease amh mRNA levels. Quantification of immunoreactive Amh and Igf3 on testis sections showed that Fsh increased slightly Igf3 staining but decreased clearly Amh staining. Studying the direct interaction of the two growth factors showed that Amh compromised Igf3-stimulated proliferation of type A (both undifferentiated [Aund] and differentiating [Adiff]) spermatogonia. Also the proliferation of those Sertoli cells associated with Aund spermatogonia was reduced by Amh. To gain more insight into how Amh inhibits germ cell development, we examined Amh-induced changes in testicular gene expression by RNA sequencing. The majority (69%) of the differentially expressed genes was down-regulated by Amh, including several stimulators of spermatogenesis, such as igf3 and steroidogenesis-related genes. At the same time, Amh increased the expression of inhibitory signals, such as inha and id3, or facilitated prostaglandin E2 (PGE2) signaling. Evaluating one of the potentially inhibitory signals, we indeed found in tissue culture experiments that PGE2 promoted the accumulation of Aund at the expense of Adiff and B spermatogonia. Our data suggest that an important aspect of Fsh bioactivity in stimulating spermatogenesis is implemented by restricting the different inhibitory effects of Amh and by counterbalancing them with stimulatory signals, such as Igf3.