视黄酸在精子发生过程中引发减数分裂的信号通路

视黄酸(RA)是维生素A即视黄醇(ROH)的一类氧化代谢产物,在哺乳动物精子发生过程(如引发减数分裂)中起着重要作用。在哺乳动物睾丸内,RA结合视黄酸受体(RAR),在不同时期、不同类型细胞中调控相应靶基因的转录表达。在特定的时期,通过上调促进减数分裂的基因表达并下调抑制减数分裂的基因表达,最终引发精子发生过程中的减数分裂。而哺乳动物精子发生的研究对生殖生物学、发育生物学、生殖工程等方面都具有广阔的应用前景,所以研究RA在哺乳动物精子发生过程中引发减数分裂的信号通路十分有意义。本文介绍了RA信号传递系统及其作用机制,并对RA在精子发生过程中引发减数分裂的信号通路进行了综述。     

双酚A对男性生殖毒性的研究进展

环境干扰物对男性生殖的毒性作用是研究热点。双酚A(BPA)是一类环境雌激素,与男性生殖健康以及其他疾病如糖尿病、肥胖、心血管疾病及癌症等相关。BPA可通过拟雌激素或抗雄激素作用干扰人体内分泌系统,如干扰下丘脑-垂体-睾丸轴、调节激素合成相关基因的表达和酶活性、影响激素及其受体功能等,也可通过修饰DNA甲基化、表观遗传效应等方式,引起生精障碍、少弱畸精子症等导致男性不育。本文综述BPA暴露对男性精子发生、精液质量及生殖内分泌系统的毒性作用。     

睾丸CR16与精子发生

精子发生是依靠各种激素(FSH、LH、T、17β雌二醇)、细胞因子和基因调节的复杂调控过程。基因调控在精子发生中的研究已逐渐成为热点,已发现的与精子发生相关的基因,如AYZ、DAZ、YRRM、NOSTRIN等。但目前关于CR16在男性生殖方面的报道尚不多见,其在精子发生中的作用机制并不十分清楚,本文主要从支持细胞形成血睾屏障角度,对CR16在男性生殖系统精子发生中的研究做一综述。     

雌激素受体在雄性生殖系统中的分布及其对雄性生殖的作用

与雄激素一样,雌激素对雄性生殖也起重要调控作用。雌激素与雌激素受体(ER)结合后,产生基因组效应或非基因组效应。ER包括ERα和ERβ。在雄性生殖系统包括睾丸、附睾、前列腺及阴茎中均有ER分布。ERα基因敲除小鼠精子发生过程明显受损,而ERβ基因敲除后小鼠精子发生仍可维持正常,提示两种ER亚型对精子发生的作用不同。ERα和ERβ还可能存在相互补偿作用。     

性激素负反馈作用在男性不育诊疗中的应用

下丘脑-垂体-睾丸轴对男性的生殖功能起着关键性作用,下丘脑和垂体共同参与调控睾丸的甾体激素合成与精子发生;复杂的刺激和反馈机制通过神经腺成分来控制激素的合成和分泌。下丘脑和垂体均有大量雄、雌激素的受体,同时受睾酮及其芳香化产物(包括雌激素)的负反馈调节。利用男性生殖内分泌轴系中的负反馈作用,通过给予抗雌激素药物或芳香化酶抑制剂,可减弱睾酮及其芳香化产物的持续负反馈调节作用,增加内源性促性腺激素的分泌,而且还能去除雌激素对生精的副作用,恢复生精或提高精液质量。     

精子发生的内分泌激素调节

下丘脑-垂体-睾丸轴系对男性生殖功能起着关键性作用,精子发生是这个轴系精密调节的结果。下丘脑促性腺激素释放激素(GnRH)脉冲式释放控制了卵泡刺激素(FSH)和黄体生成素(LH)的波动性分泌,GnRH脉冲频率的变化调节垂体促性腺细胞分泌两种不同的激素,是一种独具一格的机制。促性腺激素抑制激素(GnIH)于2000年首次从鹌鹑垂体鉴定出来。GnIH的发现使我们更深入地了解下丘脑激素对垂体促性腺细胞的调节。哺乳动物的GnIH神经元定位于下丘脑背内侧核,轴突延伸至正中隆突。GnIH通过其受体GPR147抑制垂体促性腺细胞的功能。成年男子的精子发生需要FSH和睾酮的共同作用,任何二者之一缺失会损害Sertoli细胞的分化和功能以及生精细胞在精子发生过程的发育。睾酮至少从4个方面促进精子发生:(1)紧密连接(tight junction)的形成和功能;(2)附睾的发育和功能;(3)生精细胞的发育;(4)精子释放。在体研究提示,雌激素亦对精子发生起重要作用,雌二醇调节小鼠精原细胞系和精母细胞系调亡和抗调亡之间的平衡。     

精子发生的激素调节

长期以来一致公认 ,垂体促性腺激素——卵泡刺激素 ( FSH)和黄体生成素 ( L H)所介导的睾酮 ( T)是所有哺乳动物和人类精子发生的主要调节物。然而 ,近年来大量的动物实验和一些临床研究结果对上述观点提出了至少两方面的挑战。一方面 ,睾丸产生的相当数量的雌激素也是精子发生和成熟的必须激素。因为敲除雌激素两种受体基因 ( ERαKO、ERβKO)或敲除芳香化酶基因 ( Ar KO)的雄性小白鼠均出现多种生殖功能障碍或不育。临床上也出现了因 ERα基因突变而不育的个别报道 ;另一方面 ,发现了至少已有 5例因 FSH受体 ( FSHR)基因或FSH…     

激素对精子发生的调控

精子发生是一个连续不断的细胞增生与分化的过程 ,是激素依赖的调控 ,其中卵泡刺激素 (FSH)和黄体生成素 (LH)刺激释放的睾酮 (T)是主要的激素调节者。睾丸内T是维持精子发生最关健的因素之一 ,而FSH对正常精子发生的起始和维持同样是必须的。在介导激素调节中 ,Sertoli细胞处于核心地位。同时 ,正常精子发生过程中的生精细胞凋亡也是激素调控的。深入研究精子发生的激素调控 ,为探索安全、可复的男性避孕方法奠定了基础。     

129例原发性男性不育患者的细胞遗传学分析

目前,育龄夫妇中约15%患有不育,其中近50%由男方因素造成.男性生殖是在中枢神经系统、下丘脑-垂体-睾丸性轴系的内分泌激素调节下,通过精子发生、精子成熟、精子运输、精子获能和精子顶体反应等一系列生理活动完成.精子发生受到诸多有序表达的基因控制,染色体结构、数目的畸变可影响这些基因的功能,进而影响精子发生[1].对原发性男性不育患者进行细胞遗传学分析,可明确不育病因,并为运用辅助生殖技术治疗男性不育提供遗传学依据.     

从基因敲除看生殖激素的作用

基因敲除技术已成为研究基因功能的一种重要手段 ,本综述主要介绍了雌激素受体、孕酮受体、前列腺素受体、促性腺激素释放激素、黄体生成素受体、卵泡刺激素受体、雄激素受体、催产素、泌乳素及其受体等主要的生殖激素或受体基因敲除后对小鼠生殖系统的发育、功能以及生殖行为的影响 ,并对这些激素可能的作用机理进行了讨论。     

Androgens and male fertility

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.     

表皮生长因子及其受体对雄性生殖系统的影响

表皮生长因子 (EGF)是首先从小鼠颌下腺分离出来的含 5 3个氨基酸残基的单链多肽 ,通过与其受体(EGFR)相结合发挥多种生物学效应。近年来发现 ,在人类和其他动物的雄性生殖系统有EGF与EGFR表达 ,对雄性生殖器官的发育、维持及变异起着重要的作用 ,同时 ,对雄性激素的分泌和精子发生也有很大的影响。EGFR在睾丸的支持细胞和间质细胞上均有表达 ,可影响睾酮的分泌 ;能维持正常前列腺组织的生长发育 ,刺激前列腺增生组织和前列腺癌组织的生长和分化 ;EGF参与精子发生 ,其作用点主要在减数分裂过程 ;可影响性分化 ,在雄激素诱导下使胚胎向雄性方向发育。     

Quantitative maintenance of spermatogenesis in cyclosporine-treated rats by exogenous administration of testosterone propionate

The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague-Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicles-stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose-dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA-induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.     

Tadalafil has no detrimental effect on human spermatogenesis or reproductive hormones

PURPOSE: We assessed the effects on spermatogenesis of placebo vs 10 or 20 mg tadalafil administered daily for 6 months to healthy men and men with mild erectile dysfunction. MATERIALS AND METHODS: In 2 studies 421 healthy men or men with mild erectile dysfunction who were 45 years or older and met semen criteria derived from WHO reference values were randomized to 6 months of treatment with placebo (101) or 10 mg tadalafil (103), or to placebo (106) or 20 mg tadalafil (111). Semen samples and serum for reproductive hormones (testosterone, luteinizing hormone and follicle-stimulating hormone) were collected at baseline, after 3 months and at the end of treatment. RESULTS: Tadalafil had no adverse effects on spermatogenesis, as assessed by sperm concentration, sperm count per ejaculate, percent sperm motility, normal morphology or serum reproductive hormones. Tadalafil was well tolerated. Common adverse events were headache, dyspepsia and back pain. CONCLUSIONS: Chronic daily administration of tadalafil at doses of 10 and 20 mg for 6 months had no adverse effects on spermatogenesis or on reproductive hormones in men older than 45 years.     

Infertility in spinal-cord injured male

Sterility in spinal-cord injured (SCI) men is believed to be caused by ejaculatory dysfunction, genital ductal blockage secondary to infection, and/or impaired spermatogenesis. Semen from SCI men demonstrates diminished numbers of motile, morphologically normal sperm. Testicular biopsies demonstrate impaired spermatogenesis. Leydig and Sertoli cells appear to be normal. Endocrine evaluations reveal normal testosterone levels with an adequate Leydig cell reserve. Luteinizing hormone (LD) and follicle-stimulating hormone (FSH) levels are normal or high with normal or exaggerated stimulation responses. Acute depressions in testosterone, FSH, and LH levels can be seen following SCI, most markedly in quadriplegics. A normal hypothalamic-pituitary-testicular axis is implied by these findings, indicating a primary hypogonadism. Causes of impaired spermatogenesis may include local testicular temperature elevations, nondrainage of the reproductive tract, antisperm antibodies, and recurrent genitourinary infections. Treatment of infertility involves removal of these offending factors, and research is needed to correlate the impaired spermatogenesis with these factors.     

NEW INDICATION OF TESTIS BIOPSY FOR AZOOSPERMIA: A CLINICAL STUDY IN JAPANESE PATIENTS

Because of the progress made with assisted reproductive techniques, we decided to clarify the indication for testis biopsy in Japanese azoospermic patients. A total of 88 azoospermic patients were recruited with testis histologies obtained by bilateral biopsy. Testicular histology was evaluated using Johnsen's score count. Patients with at least 1 testis containing sperm were assigned to the active spermatogenesis group. Patients whose testes had no sperm were assigned to the hypospermatogenesis group. Differences in terms of the clinical data between the 2 groups were analyzed. Clinical data consisted of past history, physical examination and hormone concentrations. The unpaired t test was generally used to examine the statistical significance of any differences between the 2 groups. 1) There were significant differences between the 2 groups in the levels of serum testosterone and luteinizing hormone. 2) There were markedly significant differences between the 2 groups in terms of testis volume and the concentration of serum follicle-stimulating hormone (FSH). 3) The smallest testis volume and the highest serum FSH value in the active spermatogenesis group were 7 ml and 32.7 mlU/ml (normal range 2.9-8.2), respectively. In conclusion, although the presence or absence of active spermatogenesis can be accurately predicted by measuring the testis volume and serum FSH, testis biopsy should be carried out in patients with a testis volume greater than 7 ml or a serum FSH less than 4 times normal when the use of assisted reproductive techniques are planned.     

Effect of nonylphenol on spermatogenesis: A systematic review

Nonylphenol (NP) is known as an environmental pollutant that has adverse effects on the spermatogenesis process. In this review, we focus on (1999–2020) studies on the effect of this pollutant on the sperm parameters and the male reproductive system. Spermatogenesis is a process in which male spermatogonia (primary germ cells) is divided into meiosis and produce spermatozoa. NP and its isomers can cause oxidative stress and alter the production of sex hormones, and thereby disrupting this vital process. By searching in the scientific databases of PubMed, Google Scholar, Science Direct, Springer and Web of Science related articles were extracted. As a result, all observations have confirmed that NP can cause multiple damages to the spermatogenesis and male reproductive system.