Muratori Monica, Baldi Elisabetta
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Department Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Front Endocrinol (Lausanne). 2018 Dec 11;9:734. doi: 10.3389/fendo.2018.00734. eCollection 2018.
Sperm DNA fragmentation (sDF) is an important reproductive problem, associated to an increased time-to-pregnancy and a reduced success rate in natural and fertilization. sDF may virtually originate at any time of sperm's life: in the testis, in the epididymis, during transit in the ejaculatory ducts and even following ejaculation. Studies demonstrate that an apoptotic pathway, mainly occurring in the testis, and oxidative stress, likely acting in the male genital tract, are responsible for provoking the DNA strand breaks present in ejaculated spermatozoa. Although several pharmacological anti-oxidants tools have been used to reduce sDF, the efficacy of this type of therapies is questioned. Clearly, anti-apoptotic agents cannot be used because of the ubiquitous role of the apoptotic process in the body. A notable exception is represented by Follicle-stimulating hormone (FSH), which regulates testis development and function and has been demonstrated to exert anti-apoptotic actions on germ cells. Here, we review the existing clinical studies evaluating the effect of FSH administration on sDF and discuss the possible mechanisms through which the hormone may reduce sDF levels in infertile subjects. Although there is evidence for a beneficial effect of the hormone on sDF, further studies with clear and univocal patient inclusion criteria, including sDF cut-off levels and considering the use of a pharmacogenetic approach for patients selection are warranted to draw firm conclusions.
精子DNA碎片化（sDF）是一个重要的生殖问题，与受孕时间延长以及自然受孕和受精成功率降低相关。sDF实际上可能在精子生命的任何阶段产生：在睾丸、附睾中，在射精管运输过程中，甚至在射精后。研究表明，主要发生在睾丸中的凋亡途径以及可能作用于男性生殖道的氧化应激，是导致射出精子中出现DNA链断裂的原因。尽管已经使用了几种药理学抗氧化剂来降低sDF，但这类疗法的疗效受到质疑。显然，由于凋亡过程在体内的普遍作用，抗凋亡药物不能使用。一个显著的例外是促卵泡生成素（FSH），它调节睾丸发育和功能，并已被证明对生殖细胞具有抗凋亡作用。在此，我们综述了评估FSH给药对sDF影响的现有临床研究，并讨论了该激素可能降低不育患者sDF水平的潜在机制。尽管有证据表明该激素对sDF有有益作用，但仍需要进一步开展研究，采用明确且统一的患者纳入标准，包括sDF临界值水平，并考虑使用药物遗传学方法进行患者选择，以便得出确凿的结论。
