Efectos a corto plazo de la RUV en la distribución vertical de Cyrtograpsus altimanus y Alexandrium tamarense de la Patagonia Atlántica

Many marine species spend part of their development in upper layers of the water column, where they may be exposed to solar ultraviolet radiation (UVR). For many of these species, light is one of the key environmental clues which triggers behaviorally-mediated adjustments in vertical distribution. We incubated planktonic larvae of the crab Cyrtograpsus altimanus in column-like aquaria to study their responses with/without UVR (under a solar simulator) and with/without a potential prey (the dinoflagellate Alexandrium tamarense). Their vertical distribution was recorded and used to evaluate the combined effects of UVR and the presence of the dinoflagellate on larval behavior. When UVR was absent, most larvae showed a tendency to swim upwards and to aggregate near the surface, regardless of the dinoflagellate presence. However, UVR inhibited this tendency and induced a repellent effect, which resulted in a more homogeneous vertical distribution of larvae. A. tamarense did not affect the vertical distribution of larvae. These results suggest that UVR-triggered, quick adjustments in vertical distribution might be an important strategy for C. altimanus larvae to cope with high solar radiation, which typically occur during the hatching season.Muchas especies marinas pasan parte de su ciclo vital en las capas superficiales de la columna de agua, donde pueden estar expuestas a radiación ultravioleta (RUV). En muchos casos la luz constituye el factor ambiental que provoca ajustes del comportamiento en la distribución vertical. Se incubaron larvas planctónicas del cangrejo Cyrtograpsus altimanus en acuarios verticales para estudiar sus respuestas con/sin RUV y con/sin una potencial presa (el dinoflagelado Alexandrium tamarense). La distribución vertical de los plancteres fue registrada y se usó para evaluar el efecto combinado de la RUV y la presencia del dinoflagelado en el comportamiento larval. Cuando la RUV estaba ausente, las larvas de C. altimanus tendieron a nadar hacia arriba y agregarse cerca de la superficie, independientemente de la presencia del dinoflagelado. Sin embargo, la RUV inhibió esta tendencia e indujo un efecto repelente que llevó a una distribución vertical de larvas mucho más homogénea. Las larvas no parecieron ser afectadas en ningún caso por la presencia de A. tamarense. Los resultados sugieren que C. altimanus podría ajustar rápidamente su distribución vertical en respuesta a RUV, lo cual sería una estrategia importante para hacer frente a los altos niveles de radiación solar que típicamente ocurren durante sus primeros estadios de desarrollo.Fil: Gonçalves, Rodrigo Javier. Fundación Playa Unión. Estación de Fotobiología Playa Unión; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Hernández Moresino, Rodrigo Daniel. Fundación Playa Unión. Estación de Fotobiología Playa Unión; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Spinelli, Mariela Lorena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biologia Experimental y Aplicada; Argentin

Diversidad de copépodos en aguas costeras de la Patagonia en el Atlántico a lo largo de un ciclo anual

El objetivo de este estudio es analizar la sucesión anual del zooplancton en una estación costera en la Patagonia (Argentina), con especial énfasis en copépodos y sus posibles presas, en relación con la radiación solar y la temperatura como factores ambientales. El ciclo anual del plancton mostró dos periodos, otoño/invierno y primavera/verano. Durante el periodo otoño/invierno, la baja temperatura y la radiación se correlacionaron con la mayor abundancia de diatomeas y la mayor diversidad de copépodos. Este periodo se caracterizó por la dominancia de la cadena clásica herbívora, y el copépodo grande Calanoides carinatus dominó la comunidad. Por el contrario, durante el periodo de primavera/verano, con alta radiación y mayores niveles de temperatura, los flagelados fueron el alimento disponible para el zooplancton y se correlacionaron con las especies pequeñas de copépodos como el harpacticoideo Euterpina acutifrons. Además, la reproducción intensiva de los copépodos pequeños E. acutifrons y Paracalanus parvus se llevó a cabo principalmente en verano. Por otro lado, se encontró una alta diversidad de especies en invierno, cuando la radiación ultravioleta fue baja. El patrón temporal de los copépodos observado en nuestro estudio fue explicado por la disponibilidad de alimento y los factores ambientales (temperatura y radiación solar), aunque otros factores tales como la abundancia de los depredadores pueden ser también importantes en la modulación de la comunidad. Nuestros resultados muestran la importancia de la dinámica de la abundancia de copépodos y destaca su papel clave en las cadenas tróficas pelágicas de las aguas costeras de la Patagonia norte.The aim of this study is to analyze the annual zooplankton succession at a coastal station in Patagonia (Argentina), with special emphasis on copepods and their potential preys, using solar radiation and temperature as environmental factors. The annual plankton cycle exhibited autumn/winter and spring/summer phases. During the autumn/winter phase, low temperature and radiation were correlated with higher diatom abundance and copepod diversity. This period was characterized by a dominant classical herbivorous food web in which the large copepod Calanoides carinatus dominated the community. On the contrary, during the spring/summer period, with high radiation and temperature levels, flagellates were the dominant food available for zooplankton and correlated with smaller species of copepods such as the harpacticoid Euterpina acutifrons. Also, intensive reproduction of the small copepods E. acutifrons and Paracalanus parvus occurred mainly in summer. On the other hand, high species diversity was found in winter when the ultraviolet radiation was low. The temporal pattern of the copepods observed in our study was explained by food availability and environmental factors (temperature and solar radiation), although other factors such as predator abundance may also be important in modulating the community. Our results show the importance of copepod abundance dynamics and highlights their key role in the pelagic food web in northern Patagonian coastal waters.Fil: Spinelli, Mariela Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Gonçalves, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Playa Unión. Estación de Fotobiología Playa Unión; ArgentinaFil: Villafañe, Virginia Estela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Playa Unión. Estación de Fotobiología Playa Unión; ArgentinaFil: Capitanio, Fabiana Lia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentin

Jellyfish biodiversity and abundance patterns in northern Patagonia (Valdés Biosphere Reserve, UNESCO 2014)

Understanding how key components of plankton food webs, such as jellyfish communities, are structured by local hydrography has important management implications for fisheries and higher trophic predators within the ecosystem. Here, we report for the first time on the jellyfish abundance, richness, and diversity distribution across the Nuevo Gulf (42° 42′S, 64° 30′W), a World Heritage Site in Argentine Patagonia and part of the Valdés Biosphere Reserve, during spring (2019 and 2020) and summer (2020 and 2021) at two depths. We found that the most abundant species was the hydromedusae Eucheilota ventricularis, followed by other Leptothecata species, representing more than 50% of the total community's abundance. Abundance and diversity were significantly higher in spring than in summer, with seasonality playing a crucial role in modulating the jellyfish community dynamics and also being related to environmental variables and other mesozooplankton groups. Variability in the abundances across the Gulf and between depths was significantly and positively associated with chlorophyll a and ammonium, but negatively correlated with temperature, agreeing with previous results for the region. Jellyfish were more abundant near the mouth of the Gulf and during spring, possibly due to the connection and exchange of colder and nutrient-enriched water masses with those coming from the continental shelf. Significant correlations were found between jellyfish species and other mesozooplankton groups in spring. Our results highlight the importance of intensifying sampling in the vertical and horizontal dimensions along an annual cycle to begin to elucidate and increase the current scarce knowledge about the jellyfish's distribution and abundance patterns in northern Patagonian gulfs.Fil: Nocera, Ariadna Celina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Dutto, María Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: D'agostino, Valeria Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; ArgentinaFil: Schloss, Irene Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina. Universidad Nacional de Tierra del Fuego; ArgentinaFil: Gonçalves, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentin

Patagonian dust as a source of macronutrients in the Southwest Atlantic ocean

The role of Patagonian wind-borne dust as a source of macronutrients to the surface waters of the Southwest Atlantic Ocean was evaluated for the first time. During spring 2016, a series of experiments with dust was conducted to evaluate the dynamics of macronutrient dissolution in seawater. The results showed a differential contribution of macronutrients to seawater depending on the dust source and the amount added. Addition of a conservative amount of Patagonian dust to the seawater contributed nitrate (NO − 3 ) and silicic acid (Si(OH) 4 ), but not phosphate (PO 4 3– ). Additional dust input to the system resulted in higher macronutrient concentrations. Particles collected from a nearby burned field did not contribute any macronutrients to the seawater. Thus, each dust event may affect biological productivity differently, depending on the source of the particles. Dissolution experiments suggest that macronutrients from dust are available immediately after particle deposition on the sea surface. The study includes field measurements of macronutrient concentrations before and after a dust storm at three nearshore marine stations. The data are consistent with macronutrient increase after the storms. Dust storms could become a very important source of nutrients to the ocean in future global warming scenarios.Fil: Paparazzo, Flavio Emiliano. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Crespi Abril, Augusto Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Gonçalves, Rodrigo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Barbieri, Elena Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Gracia Villalobos, Leilen Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Solis, Miriam Edith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Soria, Rodrigo Gaspar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentin

The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers

Càncer de mama; Genòmica del càncer; Biomarcadors tumoralsCáncer de mama; Genómica del cáncer; Biomarcadores tumoralesBreast cancer; Cancer genomics; Tumour biomarkersThe biology of breast cancer response to neoadjuvant therapy is underrepresented in the literature and provides a window-of-opportunity to explore the genomic and microenvironment modulation of tumours exposed to therapy. Here, we characterised the mutational, gene expression, pathway enrichment and tumour-infiltrating lymphocytes (TILs) dynamics across different timepoints of 35 HER2-negative primary breast cancer patients receiving neoadjuvant eribulin therapy (SOLTI-1007 NEOERIBULIN-NCT01669252). Whole-exome data (N = 88 samples) generated mutational profiles and candidate neoantigens and were analysed along with RNA-Nanostring 545-gene expression (N = 96 samples) and stromal TILs (N = 105 samples). Tumour mutation burden varied across patients at baseline but not across the sampling timepoints for each patient. Mutational signatures were not always conserved across tumours. There was a trend towards higher odds of response and less hazard to relapse when the percentage of subclonal mutations was low, suggesting that more homogenous tumours might have better responses to neoadjuvant therapy. Few driver mutations (5.1%) generated putative neoantigens. Mutation and neoantigen load were positively correlated (R2 = 0.94, p = <0.001); neoantigen load was weakly correlated with stromal TILs (R2 = 0.16, p = 0.02). An enrichment in pathways linked to immune infiltration and reduced programmed cell death expression were seen after 12 weeks of eribulin in good responders. VEGF was downregulated over time in the good responder group and FABP5, an inductor of epithelial mesenchymal transition (EMT), was upregulated in cases that recurred (p < 0.05). Mutational heterogeneity, subclonal architecture and the improvement of immune microenvironment along with remodelling of hypoxia and EMT may influence the response to neoadjuvant treatment.This work was supported by Cancer Research UK. L.D.M.A. was partly funded by Spanish Association against cancer

The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers.

The biology of breast cancer response to neoadjuvant therapy is underrepresented in the literature and provides a window-of-opportunity to explore the genomic and microenvironment modulation of tumours exposed to therapy. Here, we characterised the mutational, gene expression, pathway enrichment and tumour-infiltrating lymphocytes (TILs) dynamics across different timepoints of 35 HER2-negative primary breast cancer patients receiving neoadjuvant eribulin therapy (SOLTI-1007 NEOERIBULIN-NCT01669252). Whole-exome data (N = 88 samples) generated mutational profiles and candidate neoantigens and were analysed along with RNA-Nanostring 545-gene expression (N = 96 samples) and stromal TILs (N = 105 samples). Tumour mutation burden varied across patients at baseline but not across the sampling timepoints for each patient. Mutational signatures were not always conserved across tumours. There was a trend towards higher odds of response and less hazard to relapse when the percentage of subclonal mutations was low, suggesting that more homogenous tumours might have better responses to neoadjuvant therapy. Few driver mutations (5.1%) generated putative neoantigens. Mutation and neoantigen load were positively correlated (R2 = 0.94, p = 2 = 0.16, p = 0.02). An enrichment in pathways linked to immune infiltration and reduced programmed cell death expression were seen after 12 weeks of eribulin in good responders. VEGF was downregulated over time in the good responder group and FABP5, an inductor of epithelial mesenchymal transition (EMT), was upregulated in cases that recurred (p < 0.05). Mutational heterogeneity, subclonal architecture and the improvement of immune microenvironment along with remodelling of hypoxia and EMT may influence the response to neoadjuvant treatment

Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia

Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF.Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants.Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33-02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis.Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait

Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia

Lisbon clinical group co-authors and IVIRMA group co-authors Ana Aguiar, (Unidade de Medicina da Reproducao, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal); Carlos Calhaz-Jorge, (Unidade de Medicina da Reproducao, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal); Joaquim Nunes, (Unidade de Medicina da Reproducao, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal); Sandra Sousa (Unidade de Medicina da Reproducao, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisboa, Portugal), and Sónia Correia (Centro de Medicina Reprodutiva, Maternidade Alfredo da Costa, Centro Hospitalar Lisboa Central, Lisboa, Portugal); Maria Graça Pinto(Centro de Medicina Reprodutiva, Maternidade Alfredo da Costa, Centro Hospitalar Lisboa Central, Lisboa, Portugal). Alberto Pacheco, (IVIRMA Madrid, Spain); Cristina González, (IVIRMA Sevilla, Spain); Susana Gómez, (IVIRMA Lisboa, Portugal); David Amorós, (IVIRMA Barcelona, Spain); Jesús Aguilar, (IVIRMA Vigo, Spain); Fernando Quintana, (IVIRMA Bilbao, Spain).Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF. Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants. Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33–02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis. Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait.This work was supported by the Spanish Ministry of Science and Innovation through the Spanish National Plan for Scientific and Technical Research and Innovation (PID 2020-120157RB-I00) and the Andalusian Government through the research projects of “Plan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI 2020)” (ref. PY20_00212) and “Programa Operativo FEDER 2020” (ref. B-CTS-584-UGR20). LB-C was supported by the Spanish Ministry of Science and Innovation through the “Juan de la Cierva Incorporacion” program (Grant ref. IJC 2018-038026- I, funded by MCIN/AEI/10.13039/501100011033), which includes FEDER funds. AG-J was funded by MCIN/AEI/ 10.13039/501100011033 and FSE “El FSE invierte en tu futuro” (grant ref. FPU20/02926). IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds (projects PEstC/SAU/LA0003/2013 and POCI-01-0145-FEDER-007274). PM is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the Programa Operacional do Capital Humano. ToxOmics—Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Nova Medical School, Lisbon, is also partially supported by FCT (UID/BIM/00009/2016 and UIDB/00009/2020). SL received support from Instituto de Salud Carlos III (grant: DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe-), and from “Generalitat de Catalunya” (grant 2017SGR191). SL is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). This article is related to the Ph.D. Doctoral Thesis of AG-J.info:eu-repo/semantics/publishedVersio

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546047/Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermato genic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case–control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Tech nology and High Education and from the European Social Fund, available through the ‘Programa Operacional do Capital Humano’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health— ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).info:eu-repo/semantics/publishedVersio