Male Infertility and Its Causes in Human

Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings

Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

金沢大学医薬保健研究域医学系Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormad1 is essential for mammalian gametogenesis as knockout male mice are infertile. Hormad1-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonemal complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 (c. 163A>G), SNP2 (c. 501T>G) and SNP3 (c. 918C>T), were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest (P<0.05). We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis. © 2012 AJA, SIMM & SJTU. All rights reserved

A single nucleotide polymorphism in SPATA17 may be a genetic risk factor for Japanese patients with meiotic arrest

金沢大学医薬保健研究域医学系Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis were identified by microarray analysis of human testicular tissue. One of these is spermatogenesis-associated 17 (SPATA17). To investigate whether defects in the SPATA17 gene are associated with azoospermia due to meiotic arrest, a mutational analysis was conducted, in which the SPATA17 coding regions of 18 Japanese patients with this condition were sequenced. A statistical analysis was carried out that included 18 patients with meiotic arrest, 20 patients with Sertoli-cell-only syndrome (SCOS) and 96 healthy control men. No mutations were found in SPATA17. However, three coding single nucleotide polymorphisms (cSNPs: SNP1-SNP3) were detected in the patients with meiotic arrest. No significant differences in the genotype or allele frequencies of SNP1 and SNP2 were found between patients with meiotic arrest and the others. However, the frequency of the SNP3 allele was significantly elevated in the meiotic arrest group (P < 0.05). This study suggests that SPATA17 may play a critical role in human spermatogenesis, especially in meiosis

切迫性ならびに腹圧性尿失禁に対するプロビベリンの臨床効果に関する検討

プロピベリン(20mg/日, 28日間)の臨床効果を49名の患者を対象に多施設協同研究で調査した.排尿回数の中等度以上の改善を切迫性及び腹圧性尿失禁で52%及び54%の患者で達成出来た.尿意切迫感はそれぞれ91%及び58%の症例で改善した.尿失禁はそれぞれ97%及び71%の症例で改善した.日常生活の制限はそれぞれ94%及び64%の症例で改善が見られた.軽度の副作用を5名に, 臨床検査値の変動を2名に認めたThe efficacy and tolerability of propiverine hydrochloride (20 mg/day) were evaluated in the treatment of a total of 49 Japanese patients (35 with urge incontinence and 14 with stress incontinence) in an open multicenter trial lasting 28 days. The effects on the frequency of urination, urinary incontinence, urinary urgency, and daily living activities were evaluated through the voiding diaries filled out by the patients. Moderate or greater degree of improvement was attained in micturition frequency by 52 and 54% of the patients with urge incontinence and with stress incontinence, respectively, in urinary urgency by 91 and 58%, in urinary incontinence by 97 and 71%, and in daily living activities by 94 and 64%. Although minor adverse reactions (5 patients) and abnormal values in blood chemistry (2 patients) were recorded in 7 patients, all of these patients completed the trial. These results suggest that propiverine hydrochloride is a safe and effective drug of choice for the treatment of not only urge incontinence but also stress incontinence in patients diagnosed in a clinical setting

学会の動向：第47回日本化学療法学会東日本支部総会 合同学会を終えて

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生殖医療補助技術の現状と展望

出版社版世界初の体外受精児の誕生からわずか20数年の間に、生殖医療補助技術(Assisted reproductive technology:ART)は不妊治療法として急速に臨床に普及し、従来、妊娠が困難であった難治性不妊患者に多くの福音をもたらした。一方、多胎妊娠、未熟児出産の増加、卵巣過剰刺激症候群発症などの弊害も生まれた。また、新たな生命倫理に関わる問題も提起されるようになり、早急に解決すべき多くの課題が残されている現状にある。近年、胞胚移植、assisted hatching技術の導入により妊娠率の向上を認めるが、本邦における生産率は未だ20%前後と低値である。さらには、高齢婦人、精子、卵子が先天的、後天的に欠如した症例、悪性腫瘍で抗癌剤治療を必要とする患者の妊孕性の確保・温存など今後のさらなる技術革新が期待される

学会の動向：第19回日本産婦人科感染症研究会

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