RESUMO
Objective: To study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men. METHODS: This case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software. RESULTS: There were statistically significant differences between the control and infertility groups in the semen volume (ï¼»3.51 ± 1.36ï¼½ vs ï¼»3.74 ± 1.71ï¼½ ml, P <0.05), sperm concentration (ï¼»79.21 ± 61.60ï¼½ vs ï¼»27.37 ± 30.80ï¼½ ×106/ml, P <0.01), percentage of progressively motile sperm (ï¼»39.40 ± 9.64ï¼½ % vs ï¼»11.90 ± 14.72ï¼½ %, P <0.01), and levels of serum luteinizing hormone (LH) (ï¼»3.29 ± 1.39ï¼½ vs ï¼»6.25 ± 4.83ï¼½ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (ï¼»4.56 ± 2.31ï¼½ vs ï¼»15.64 ± 17.03ï¼½ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility. CONCLUSIONS: The rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.
Assuntos
Infertilidade Masculina/genética , Hormônio Luteinizante Subunidade beta/genética , Polimorfismo de Nucleotídeo Único , Adulto , Azoospermia/genética , Estudos de Casos e Controles , China , Hormônio Foliculoestimulante , Genótipo , Haplótipos , Humanos , Modelos Logísticos , Hormônio Luteinizante , Masculino , Oligospermia/genética , Contagem de EspermatozoidesRESUMO
<p><b>Objective</b>To study the relationship of the single nucleotide polymorphisms (SNP) rs34349826 (c.104 A>G) and rs6521 (c.114 C>G) of the luteinizing hormone beta-subunit (LHB) gene with male infertility in Chinese men.</p><p><b>METHODS</b>This case-control study included 405 males with primary infertility (the infertility group) and 424 normal fertile men (the control group), the former again divided into subgroups of oligospermia, severe oligozoospermia and azoospermia according to the sperm concentration. Clinical data were collected from all the subjects and genomic DNA obtained from their peripheral blood for genotyping rs34349826 and rs6521 of the LHB gene by Sequence MassArray. We analyzed the correlation of male infertility with the SNPs of the two loci using the logistic regression model as well as its association with their haplotype combination with the SHEsis online software.</p><p><b>RESULTS</b>There were statistically significant differences between the control and infertility groups in the semen volume (［3.51 ± 1.36］ vs ［3.74 ± 1.71］ ml, P <0.05), sperm concentration (［79.21 ± 61.60］ vs ［27.37 ± 30.80］ ×10⁶/ml, P <0.01), percentage of progressively motile sperm (［39.40 ± 9.64］ % vs ［11.90 ± 14.72］ %, P <0.01), and levels of serum luteinizing hormone (LH) (［3.29 ± 1.39］ vs ［6.25 ± 4.83］ IU/L, P <0.01) and follicle-stimulating hormone (FSH) (［4.56 ± 2.31］ vs ［15.64 ± 17.03］ IU/L, P <0.01). Logistic regression analysis revealed no correlation between male infertility and the genotypes of the rs34349826 and rs6521 loci of the LHB gene, and similar results were found in the subgroups of the infertile males. SHEsis analysis on the haplotypes of the rs34349826 and rs6521 loci showed the GG genotype combination to be a protective factor against male infertility.</p><p><b>CONCLUSIONS</b>The rs34349826 and rs6521 loci of the LHB gene were not related to male infertility, which can be further confirmed by larger-sample studies. The GG genotype combination is a protective factor against male infertility.</p>
Assuntos
Adulto , Humanos , Masculino , Azoospermia , Genética , Estudos de Casos e Controles , China , Hormônio Foliculoestimulante , Genótipo , Haplótipos , Infertilidade Masculina , Genética , Modelos Logísticos , Hormônio Luteinizante , Hormônio Luteinizante Subunidade beta , Genética , Oligospermia , Genética , Polimorfismo de Nucleotídeo Único , Contagem de EspermatozoidesRESUMO
Luteinizing hormone beta polypeptide (LHB) gene has been considered important for sexual behavior and has associations with sperm quality. In this study, four SNPs (g.276 T>C, g.377A>C, g.401T>C, and g.412A>G) were detected in the LHB gene of 165 water buffaloes by direct sequencing and identification of overlap peaks, each of which was associated with at least one sperm quality trait of ejaculate volume, sperm concentration, post-thaw sperm motilities, and sperm abnormalities by chi-square analysis. Among them, g.276 T>C was associated with ejaculate volume (F = 2.857, p < 0.05), sperm concentration (F = 2.052, p < 0.05), and post-thaw sperm motilities (F = 3.480, p < 0.05); g.377A>C was related to ejaculate volume (F = 4.178, p < 0.05), g.401T>C had a marker effect on sperm abnormalities (F = 3.332, p < 0.05), g.412A>G was associated with sperm concentration (F = 3.579, p < 0.05), and sperm abnormalities (F = 3.408, p < 0.05). Furthermore, four haplotypes (H1: ACG, H2: CCG, H3: CTA, H4: CCA) were generated by linkage disequilibrium analysis, which composed seven genotypes. Among them, the buffaloes with combined genotype H2H2 had the higher ejaculate volume and the individuals with the combined haplotypes H1H4 had higher sperm concentration. In summary, our study showed that there was a significant association between SNPs of LHB gene and Chinese water buffalo sperm quality traits. To the best of our knowledge, this is the first report addressing the associations between the SNPs in the LHB gene and the sperm qualities of Chinese buffaloes.
Assuntos
Búfalos/genética , Hormônio Luteinizante Subunidade beta/genética , Polimorfismo de Nucleotídeo Único/genética , Espermatozoides/fisiologia , Animais , Haplótipos/genética , Desequilíbrio de Ligação , MasculinoRESUMO
Luteinizing hormone (LH) is a pituitary heterodimeric glycoprotein essential in male and female reproduction. Its functional polymorphic variant (V-LH) is determined by two missense mutations (rs1800447, A/G, Trp8Arg; rs34349826, A/G, Ile15Thr) in the LH ß-subunit encoding gene (LHB; 19q13.3; 1111 bp; 3 exons). Among women, V-LH has been associated with higher circulating LH and reduced fertility, but the knowledge of its effect on male reproductive parameters has been inconclusive. The objective of this study was to assess the effect of V-LH on hormonal, seminal and testicular parameters in the Baltic young men cohort (n = 986; age: 20.1 ± 2.1 years) and Estonian idiopathic infertility patients (n = 607; 35.1 ± 5.9 years). V-LH was detected by genotyping of the underlying DNA polymorphisms using PCR-RFLP combined with resequencing of a random subset of subjects. Genetic associations were tested using linear regression under additive model and results were combined in meta-analysis. No significant difference was detected between young men and infertility patients for the V-LH allele frequency (11.0 vs. 9.3%, respectively). V-LH was associated with higher serum LH in both, the young men cohort (p = 0.022, allelic effect = 0.26 IU/L) and the idiopathic infertility group (p = 0.008, effect = 0.59 IU/L). In meta-analysis, the statistical significance was enhanced (p = 0.0007, resistant to Bonferroni correction for multiple testing; effect = 0.33 IU/L). The detected significant association of V-LH with increased serum LH remained unchanged after additional adjustment for the SNPs previously demonstrated to affect LH levels (FSHB -211G/T, FSHR Asn680Ser, FSHR -29A/G). Additionally, a suggestive trend for association with reduced testicular volume was observed among young men, and with lower serum FSH among infertility patients. The V-LH carrier status did not affect sperm parameters and other circulating reproductive hormones. For the first time, we show a conclusive contribution of V-LH to the natural variance in male serum LH levels. Its downstream clinical consequences are still to be learned.
Assuntos
Hormônio Luteinizante Subunidade beta/sangue , Hormônio Luteinizante Subunidade beta/genética , Oligospermia/sangue , Envelhecimento , Estônia , Feminino , Hormônio Foliculoestimulante/sangue , Frequência do Gene/genética , Humanos , Masculino , Mutação/genética , Oligospermia/genética , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Contagem de Espermatozoides , Testículo/fisiologia , Testosterona/sangueRESUMO
Pasqualini and Bur published the first case of eunuchoidism with preserved spermatogenesis in 1950 in Revista de la Asociación Médica Argentina. The hypoandrogenism with spermatogenesis syndrome included: (a) eunuchoidism, (b) testis with normal spermatogenesis and full volume, with mature spermatozoa in a high proportion of seminiferous tubes and undifferentiated and immature Leydig cells (c) full functional compensation through the administration of chorionic gonadotropin hormone, while hCG is administered (d) total urinary gonadotrophins within normal limits (e) this definition supposes the normal activity of the pituitary and the absence of congenital malformations in general. A first step in the understanding of the physiopathogeny of Pasqualini syndrome or the so called "fertile eunuch" syndrome was the absence of LH in plasma and urine of patients. The second breakthrough was the functional and genetic studies that validated the hypothesis of a functional deficit of LH in these men: it will then also be described in some women. Different groups including ours demonstrated in these cases a LH with varying degrees of immunological activity but biologically inactive in most of the patients, due to one or more inactivating mutations in the LHB gene. Finally, the full comprehension of Pasqualini syndrome allowed to reverse the hypoandrogenic phenotype and to restore fertility in these patients through the use of chorionic gonadotropin and the modern in-vitro fertility techniques. This article is an historical review and a tribute to the memory of Rodolfo Q. Pasqualini.
Assuntos
Eunuquismo/história , Hormônio Luteinizante/genética , Espermatogênese/fisiologia , Argentina , Gonadotropina Coriônica/uso terapêutico , Feminino , História do Século XX , História do Século XXI , Homozigoto , Humanos , MasculinoRESUMO
Pasqualini y Bur publican el primer caso de eunucoidismo con espermatogénesis conservada en 1950 en la Revista de la Asociación Médica Argentina. El síndrome de hipoandrogenismo con espermatogénesis incluye: (a) eunucoidismo bien definido, (b) testículos de volumen normal con espermatogénesis completa, llegando a espermatozoides maduros en una elevada proporción de tubos seminíferos, con células de Leydig indiferenciadas e inmaduras, (c) compensación funcional completa mediante la administración de gonadotrofina coriónica, mientras ésta se aplique (d) gonadotrofinas urinarias totales dentro de límites normales, y (e) esta definición fue ampliada con la actividad normal de las otras hormonas adenohipofisarias y la ausencia de malformaciones congénitas en la mayoría de los casos. En la fisiopatogenia del síndrome de Pasqualini, conocido también como síndrome del "eunuco fértil", se demostró primero la ausencia de hormona luteinizante (LH) en el plasma y orina de estos pacientes. El segundo gran avance fueron los estudios funcionales y genéticos que validaron la hipótesis de un déficit funcional de LH en estos hombres, extendido luego a las mujeres. Varios grupos, incluyendo el nuestro, demostrarían en estos casos una LH con diferentes grados de actividad inmunológica pero biológicamente inactiva, a partir de una o más mutaciones invalidantes en el gen LHB. Por último, la comprensión acabada del síndrome de Pasqualini permitiría revertir el fenotipo y la infertilidad de estos pacientes a partir de la utilización de gonadotrofina coriónica y las modernas técnicas de fertilidad in vitro. Este artículo es una revisión histórica y un homenaje a la memoria de Rodolfo Q. Pasqualini.(AU)
Pasqualini and Bur published the first case of eunuchoidism with preserved spermatogenesis in 1950 in Revista de la Asociación Médica Argentina. The hypoandrogenism with spermatogenesis syndrome included: (a) eunuchoidism, (b) testis with normal spermatogenesis and full volume, with mature spermatozoa in a high proportion of seminiferous tubes and undifferentiated and immature Leydig cells (c) full functional compensation through the administration of chorionic gonadotropin hormone, while hCG is administered (d) total urinary gonadotrophins within normal limits (e) this definition supposes the normal activity of the pituitary and the absence of congenital malformations in general. A first step in the understanding of the physiopathogeny of Pasqualini syndrome or the so called "fertile eunuch" syndrome was the absence of LH in plasma and urine of patients. The second breakthrough was the functional and genetic studies that validated the hypothesis of a functional deficit of LH in these men: it will then also be described in some women. Different groups including ours demonstrated in these cases a LH with varying degrees of immunological activity but biologically inactive in most of the patients, due to one or more inactivating mutations in the LHB gene. Finally, the full comprehension of Pasqualini syndrome allowed to reverse the hypoandrogenic phenotype and to restore fertility in these patients through the use of chorionic gonadotropin and the modern in-vitro fertility techniques. This article is an historical review and a tribute to the memory of Rodolfo Q. Pasqualini.(AU)
RESUMO
Pasqualini y Bur publican el primer caso de eunucoidismo con espermatogénesis conservada en 1950 en la Revista de la Asociación Médica Argentina. El síndrome de hipoandrogenismo con espermatogénesis incluye: (a) eunucoidismo bien definido, (b) testículos de volumen normal con espermatogénesis completa, llegando a espermatozoides maduros en una elevada proporción de tubos seminíferos, con células de Leydig indiferenciadas e inmaduras, (c) compensación funcional completa mediante la administración de gonadotrofina coriónica, mientras ésta se aplique (d) gonadotrofinas urinarias totales dentro de límites normales, y (e) esta definición fue ampliada con la actividad normal de las otras hormonas adenohipofisarias y la ausencia de malformaciones congénitas en la mayoría de los casos. En la fisiopatogenia del síndrome de Pasqualini, conocido también como síndrome del "eunuco fértil", se demostró primero la ausencia de hormona luteinizante (LH) en el plasma y orina de estos pacientes. El segundo gran avance fueron los estudios funcionales y genéticos que validaron la hipótesis de un déficit funcional de LH en estos hombres, extendido luego a las mujeres. Varios grupos, incluyendo el nuestro, demostrarían en estos casos una LH con diferentes grados de actividad inmunológica pero biológicamente inactiva, a partir de una o más mutaciones invalidantes en el gen LHB. Por último, la comprensión acabada del síndrome de Pasqualini permitiría revertir el fenotipo y la infertilidad de estos pacientes a partir de la utilización de gonadotrofina coriónica y las modernas técnicas de fertilidad in vitro. Este artículo es una revisión histórica y un homenaje a la memoria de Rodolfo Q. Pasqualini.
Pasqualini and Bur published the first case of eunuchoidism with preserved spermatogenesis in 1950 in Revista de la Asociación Médica Argentina. The hypoandrogenism with spermatogenesis syndrome included: (a) eunuchoidism, (b) testis with normal spermatogenesis and full volume, with mature spermatozoa in a high proportion of seminiferous tubes and undifferentiated and immature Leydig cells (c) full functional compensation through the administration of chorionic gonadotropin hormone, while hCG is administered (d) total urinary gonadotrophins within normal limits (e) this definition supposes the normal activity of the pituitary and the absence of congenital malformations in general. A first step in the understanding of the physiopathogeny of Pasqualini syndrome or the so called "fertile eunuch" syndrome was the absence of LH in plasma and urine of patients. The second breakthrough was the functional and genetic studies that validated the hypothesis of a functional deficit of LH in these men: it will then also be described in some women. Different groups including ours demonstrated in these cases a LH with varying degrees of immunological activity but biologically inactive in most of the patients, due to one or more inactivating mutations in the LHB gene. Finally, the full comprehension of Pasqualini syndrome allowed to reverse the hypoandrogenic phenotype and to restore fertility in these patients through the use of chorionic gonadotropin and the modern in-vitro fertility techniques. This article is an historical review and a tribute to the memory of Rodolfo Q. Pasqualini.
Assuntos
Feminino , História do Século XX , História do Século XXI , Humanos , Masculino , Eunuquismo/história , Hormônio Luteinizante/genética , Espermatogênese/fisiologia , Argentina , Gonadotropina Coriônica/uso terapêutico , HomozigotoRESUMO
INTRODUCTION: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial etiology, which affects 6-10% of women of reproductive age. It is considered the leading cause of anovulatory infertility, menstrual disorders and hyperandrogenism in this population. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the heterogenic presentation of the disease. MATERIALS AND METHODS: 130 Brazilian women, aged 14-42 years, who met the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy women constituted the control group. Presence of hirsutism was classified using the modified Ferriman-Gallwey score (F-G score) as absent (≤7), mild (8-14), and severe (≥15). Blood levels of luteinizing hormone (LH), total testosterone (TT), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified and sequenced. Differences in allelic and genotypic frequency distribution of each polymorphism across controls and cases were estimated by the Mantel-Haenszel chi-square or Fisher's exact test (p<0.05), and the probability of an association between the detection of a polymorphism and presence of a diagnosis of PCOS, by logistic regression. RESULT(S): Sequencing detected 8 polymorphisms in the LHB gene coding region. Two polymorphisms in linkage disequilibrium were significantly more prevalent in the presence of hyperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.02). CONCLUSION(S): In this series, a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS was observed; however, this finding needs to be replicated in other populations.
