Zdrojewicz Zygmunt, Konieczny Radosław, Papier Paulina, Szten Filip
Department of Endocrinology, Diabetes and Radionuclide Therapy, Wroclaw Medical University, Poland.
Students of Medical Department, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2015 Jul-Aug;24(4):705-14. doi: 10.17219/acem/33827.
Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper). Both are responsible for sperm motility. Drugs such as thioridazine used in schizophrenia treatment and phenoxybenzamine (antihypertensive activity) exhibit a contraceptive effect. Similar action exhibits an analogue of lonidamine--adjudin and an antagonist of retinoic acid receptors (BMS-189453). Researchers are working on a contraceptive vaccine, whose active ingredient is epididymal protease inhibitor (Eppin). Another promising method acts by blocking Bromodomain testis-specific proteins (Brdt) involved in the process of spermatogenesis. JQ1-the Brdt inhibitor causes reversible infertility without affecting the endocrine signaling pathways. A recent discovery of Juno as the binding partner for Izumo1 identifies these proteins as the cell-surface receptor pair, essential for gamete recognition and this interaction can be inhibited by an anti-Juno monoclonal antibody. Our review shows that the situation of men can change and investigators are close to the optimal solution. In the near future men will be able to choose the best contraceptive suited to their needs.
与高效且安全的女性避孕方法相比，输精管切除术和避孕套是男性仅有的选择。男性避孕方法的选择有限，所以避孕主要落在女性肩上。人们考虑了几种概念：给予睾酮——抑制垂体分泌促黄体生成素（LH）和促卵泡生成素（FSH），给予孕激素——影响促性腺激素和促性腺激素释放激素（GnRH）拮抗剂的分泌。发现了非激素男性避孕的新潜在靶点：甘油醛 - 3 - 磷酸脱氢酶（GAPDHS）——男性生殖细胞特有的，以及电压门控阳离子通道（CatSper）。两者都负责精子的运动。用于治疗精神分裂症的药物如硫利达嗪和苯氧苄胺（具有抗高血压活性）具有避孕作用。类似的作用还表现于洛尼达明类似物——阿地君和视黄酸受体拮抗剂（BMS - 189453）。研究人员正在研发一种避孕疫苗，其活性成分是附睾蛋白酶抑制剂（Eppin）。另一种有前景的方法是通过阻断参与精子发生过程的睾丸特异性溴结构域蛋白（Brdt）起作用。Brdt抑制剂JQ1可导致可逆性不育而不影响内分泌信号通路。最近发现Juno是Izumo1的结合伴侣，确定这些蛋白质为细胞表面受体对，对配子识别至关重要，并且这种相互作用可被抗Juno单克隆抗体抑制。我们的综述表明男性的情况可能会改变，研究人员已接近最佳解决方案。在不久的将来，男性将能够选择最适合其需求的最佳避孕方法。
