Correlation of the single nucleotide polymorphisms rs34349826 and rs6521 of the LHB gene with male infertility in Chinese men / 中华男科学杂志

<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>

Effects of ghrelin on sexual behavior and luteinizing hormone beta-subunit gene expression in male rats

Background: The hormones of hypothalamo-pituitary-gonadal [HPG] axis have facilitative effects on reproductive behavior in mammals. Ghrelin as a starvation hormone has an inhibitory effect on HPG axis' function. Hence, it is postulated that ghrelin may reduce the sexual behavior through inhibiting of HPG axis. The aim of this study was to examine the effects of ghrelin and its antagonist, [D-Lys3]-GHRP-6, on sexual behavior and LH beta-subunit gene expression in male rats

Methods: In this experimental study, 128 male Wistar rats were divided into two groups. Each group was further subdivided into eight subgroups [n=8 rats/subgroup] including the animals that received saline, ghrelin [2, 4 or 8 nmol], [D-Lys3]-GHRP-6 [5 or 10 nmol] or co-administration of ghrelin [4 nmol] and [D-Lys3]-GHRP-6 [5 or 10 nmol] through the stereotaxically implanted cannula into the third cerebral ventricle. The sexual behavior of male rats encountering with females and the hypophyseal LH beta-subunit gene expression were evaluated at two different groups

Data were analyzed by ANOVA and p<0.05 was considered statistically significant. Results: Ghrelin injection [4 and 8 nmol] significantly [p<0.01] increased the latencies to the first mount, intromission and ejaculation as well as the post-ejaculatory interval. Also, 4 and 8 nmol ghrelin significantly [p<0.05] increased the number of mount and decreased the number of ejaculation. In co-administrated groups, [DLys3]- GHRP-6 antagonized the effects of ghrelin. Ghrelin injection [4 and 8 nmol] reduced the LH beta-subunit gene expression while pretreatment with [D-Lys3]- GHRP-6 improved the gene expression

Conclusion: Ghrelin decreased the sexual behavior and LH beta-subunit gene expression in male rats, whereas [D-Lys3]-GHRP-6 antagonizes these effects

luteinizing hormone beta-subunit exon 3 [Gly102Ser] gene mutation and ovarian responses to controlled ovarian hyperstimulation

Despite extensive progress in IVF techniques, one of the most difficult problems is the variability in the response to controlled ovarian hyperstimulation [COH]. Recent studies show the effects of individual genetic variability on COH outcome. To evaluate the correlation between LHbeta G1502A polymorphisms in exon 3 of the LH gene and ovarian response to COH. A total of 220 women treated with a long protocol for ovarian stimulation were studied. Three genotypes of GG, GA and AA were detected by polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] analysis. In total, 34 [17%] patients were poor responders, 154 [77%] were normal responders and 12 [6%] were hyper responders. The most frequent genotype was GA [55.5%] whereas 44.5% of patients showed GG genotype and there was no patient with AA genotype. In total 54.5% of normal responders, 61.8% of poor responders and 50% of hyper responders showed GA genotype. Our results did not establish a significant relationship between this polymorphism and the ovarian response. Therefore it is still very difficult to use the genotype of patients for prediction of the ovarian response to stimulation

Genome association analysis for pregnancy status following parturition in crossbred beef cattle / Estudo de associação genômica de prenhez pós-parto em vacas de corte

The aim of this study was to evaluate genetic diversity of nine molecular markers, six short tandem repeats - STRs (BM4325, BMS3004, ILSTS002, IDVGA51, HEL5, AFZ1) and three single nucleotide polymorphisms (SNPs; LepSau3A1 A-B, LepSau3A1 1-2, and FSHRAlu1), linked to genes involved in reproductive function and their possible effect on reproductive performance. For this purpose, 81 crossbred beef cows were used in this study. The animals were classified into two groups (fertile and sub-fertile cows) based on their pregnancy status after two breeding seasons. High genetic diversity level was observed highlighted by the polymorphic content information ranging 0.23 to 0.87 and expected heterozygosity from 27 to 89%, with an average of 62%. Alleles BM4325 103, BMS3004 129, ILSTS002 137, IDVGA51 177, LEPSau3A1 A, LEPSau3A1 1, HEL5 149, AFZ1 119 and FSHRAlu1 G presented high frequencies. Two STRs (IDVGA51 and ILSTS002), linked to Leptin and LH genes, respectively, were associated to reproductive performance. These data support previous findings suggesting the potential use of IDVGA51 and ILSTS002 STRs for reproductive performance selection.

Foi avaliada a diversidade genética de nove marcadores moleculares, dos quais seis do tipo short tandem repeats - STR (BM4325, BMS3004, ILSTS002, IDVGA51, HEL5, AFZ1) e três do tipo single nucleotide polymorphisms - SNPs (LepSau3A1 A-B, LepSau3A1 1-2 e FSHRAlu1), ligados a genes envolvidos na reprodução e seus efeitos na performance reprodutiva. Foram examinadas amostras de sangue de 81 vacas sem raça definida, os animais foram classificados em dois grupos (vacas férteis e subférteis) baseado nas taxas de prenhez de duas estações reprodutivas. Alto nível de diversidade genética foi observado, revelando alto conteúdo de informação polimórfica, variando de 0,23 a 0,87 e heterozigosidade esperada de 27 a 89% com 62% em média. Os alelos mais frequentes foram BM4325 103*, BMS3004 129*, ILSTS002 137*, IDVGA51 177*, LEPSau3A1 A, LEPSau3A1 1, HEL5 149*, AFZ1 119* e FSHRAlu1 G. Os marcadores IDVGA51 e ILSTS002, ligados aos genes da leptina e LH, respectivamente, foram associados a performance reprodutiva. Esses dados suportam achados prévios que sugerem o potencial uso desses marcadores na seleção de animais com maior performance reprodutiva.

Función hormonal y flujo sanguíneo útero-ovárico en pacientes sometidos a salpingectomía / Hormonal function and uterine and ovary blood flow in patients under salpingectomy

El objetivo de la investigación fue comparar los efectos de la salpingectomía sobre la función hormonal y el flujo sanguíneo útero-ovárico. Se incluyeron 33 mujeres sanas con ciclos menstruales regulares. La salpingectomía fue realizada inmediatamente en los 5 días siguientes a la menstruación. Se tomaron muestras de sangre venosa para determinar las concentraciones de las hormonas folículo estimulante y luteinizante, estradiol y progesterona antes y luego de 3 meses de la cirugía. El flujo sanguíneo fue evaluado usando Doppler color y de pulso para medir el índice de resistencia, índice de pulsatilidad y velocidad sistólica pico en la vasculatura ovárica y las arterias uterinas. Se observó un aumento estadísticamente significativo en las concentraciones de hormonas folículo estimulante y luteinizante después de 3 meses de la salpingectomía (P<0,05). No se encontraron diferencias estadísticas significativas en las concentraciones de estradiol y progesterona (P=ns). Se observaron variaciones estadísticas significativas en los valores de velocidad sistólica pico, índice de resistencia e índice de pulsatilidad de la arteria ovárica al comparar los valores antes y 3 meses después de la salpingectomia (P<0,05). También se observó un aumento estadísticamente significativo en el volumen de los ovarios después de 3 meses de la cirugía (P<0,05). Se concluye que luego de 3 meses, la salpingectomía produce cambios en las concentraciones de gonadotropinas, tamaño de los ovarios y en los parámetros ecográficos Doppler de las arterias ováricas

The objetive of research was to compare the effects of salpingectomy over hormonal function and uterine and ovary blood flow. Thirty-three healthy women with normal menstrual cycles were included. Salpingectomy was performed immediately in five days following menstruation. A venous blood sample was taken to determine folicular stimulant and luteinizant hormones, estradiol and progesterone before and after three months of surgery. Bood flow was evaluated using color and pulse Doppler to measure resistance index, pulsatility index and peak systolic flow in ovary vasculare and uterine artery. There were statically significant increased in folicular stimulant and luteinizant hormones concentrations after three months of salpingectomy (P<0.05). There were not significant differences in estradiol and progesterone concentrations (P=ns). There were statistically significant variations in values of peak systolic flow, resistance index and pulsatility index of ovarian arteries when values before and three moths after salpingectomy were compared (P<0.05). There was also a statistically significant increase in ovary volume after three months of surgery (P=0.05). It is concluded that after three months, salpingectomy produces changes in gonadotropins concentrations, ovary size and ultrasound Doppler parameters of ovarian artery

Hipogonadismo hipogonadotrófico: diagnóstico pré-puberal e papel das isoformas e variantes gênicas do hormônio luteinizante no fenótipo da doença / Hypogonadotropic hypogonadism: pre-pubertal diagnosis and the role of the isoforms and allelic variants of the luteinizing hormone in the disease phenotype

A resposta do LH e do FSH ao estímulo com GnRH, realizado em estádio pré-puberal em pacientes com hipopituitarismo acompanhados até a idade puberal, são úteis para predizer o diagnóstico da deficiência de gonadotrofinas, principalmente nas meninas. O estudo da região codificadora do gene LH em pacientes com hipogonadismo hipogonadotrófico e concentrações normais de LH revelou 5 variantes alélicas. A freqüência das variantes alélicas Arg8 e Thr15 foi similar entre hipogonádicos e adultos normais e a sua presença não interferiu nas concentrações séricas do LH. O estudo das isoformas do LH mostrou um predomínio das isoformas ácidas do LH em hipogonádicos e indivíduos normais, não permitindo atribuir à sua presença a baixa atividade biológica do LH imunorreativo encontrado em 13 por cento dos hipogonádicos / LH and FSH responses to GnRH stimulation carried out in the pre-pubertal stage in patients with hypopituitarism followed until the pubertal stage are useful tools for predicting the gonadotropin deficiency diagnosis, especially in girls. The study of the codifying region of the LH gene in patients with hypogonadotropic hypogonadism and normal LH levels disclosed 5 allelic variants. The frequencies of the allelic variants Arg8 and Thr15 were similar between hypogonadic and normal adults, and their presence did not alter serum LH levels. The study of LH isoforms showed a predominance of acid LH isoforms in hypogonadic and normal subjects, which does not allow us to ascribe to their presence the low biological activity of the immunoreactive LH, found in 13 per cent of the hypogonadic individuals...

Frequency of the allelic variant (Trp8Arg/Ile15Thr) of the luteinizing hormone gene in a Brazilian cohort of healthy subjects and in patients with hypogonadotropic hypogonadism

OBJETIVO: Avaliar a freqüência da variante alélica (Trp8Arg/Ile15Thr) do gene da subunidade b do hormônio luteinizante em um grupo de brasileiros saudáveis e em pacientes portadores de hipogonadismo hipogonadotrófico.CASUÍSTICA E MÉTODOS: Duzentos e dois adultos (115 mulheres) com função sexual preservada e 48 pacientes (24 mulheres) portadoras de hipogonadismo hipogonadotrófico foram submetidos a estudo molecular utilizando técnicas de reação em cadeia da polimerase seguida por digestão enzimática com as enzimas de restrição Nco I (para detecção da mutação pontual Trp8Arg) e Fok I (para detecção da mutação pontual Ile15Thr). Os níveis basais de hormônio luteinizante e FSH, testosterona ou estradiol foram dosados em 37 indivíduos normais (21 mulheres) e 27 pacientes portadores de hipogonadismo hipogonadotrófico (13 mulheres) pelo método imunofluorométrico (hLH-Spec and hFSH-Spec, AutoDELFIA, Wallac Oy, Turku, Finland).RESULTADOS: A variante alélica (Arg8/Thr15) do gene da subunidade b do LH apresentou freqüência similar nos indivíduos saudáveis (14.4%) e nos pacientes portadores de hipogonadismo hipogonadotrófico (16.6%). Não houve interferência da variante alélica do gene da subunidade b do LH nos níveis de LH dos indivíduos normais e dos pacientes portadores de hipogonadismo hipogonadotrófico.CONCLUSÃO: Este estudo indica que a variante alélicaArg8/Thr15 do gene da subunidade b do LH é um polimorfismo comum na população brasileira (14.4%). A freqüência similar dessa variante em indivíduos saudáveis e em portadores de hipogonadismo hipogonadotrófico exclui o papel da variante na etiologia do hipogonadismo hipogonadotrófico.

LH-Beta Gene Analysis in Infertility Patients / 대한산부인과학회잡지

No abstract available.