BACKGROUND & AIMS: :Antifertility efficacy of oral administration of aqueous fruit extract of Mimusops elengi (200, 400 and 600 mg kg(-1) body weight/day for 35 days) was evaluated in Parkes strain male mice. Various reproductive end points such as histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and fertility indices were assessed; activities of 3β- and 17β-hydroxysteroid dehydrogenases, and immunoblot expressions of StAR and P450scc in the testis were also assessed. Histologically, testes in Mimusops-treated mice showed nonuniform and diverse degenerative changes in the seminiferous tubules; both affected and normal tubules were observed in the same sections of testis. The treatment had adverse effects on testicular hydroxysteroid dehydrogenases and StAR and P450scc, serum level of testosterone and on motility, viability and number of spermatozoa in cauda epididymis. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected by the treatment. Also, libido was not affected in treated males, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, the alterations caused in the above parameters recovered to control levels, suggesting that Mimusops treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Further, there were no detectable signs of toxicity in treated males.

背景与目标： ：在Parkes品系雄性小鼠中评估了口服Mimusops elengi水果水提取物（200、400和600 mg kg（-1）体重/天持续35天）的抗生育功效。评估了各种生殖终点，例如组织病理学，精子参数，睾丸激素水平，血液学，血清生化指标和生育指数。还评估了3β-和17β-羟基类固醇脱氢酶的活性以及StAR和P450scc在睾丸中的免疫印迹表达。从组织学的角度看，用Mimusops处理的小鼠的睾丸在曲细精管中显示出不均匀且多样的变性变化。在睾丸的同一部分观察到了受影响的和正常的肾小管。该疗法对睾丸羟类固醇脱氢酶和StAR和P450scc，血清睾丸激素水平以及附睾马尾精子的活力，生存力和精子数量有不利影响。但是，该治疗不会影响血清丙氨酸转氨酶，天冬氨酸转氨酶和肌酐的水平以及血液学参数。同样，性欲受治疗的男性并未受到影响，但其生育能力明显受到抑制。停药56天后，上述参数引起的改变恢复到控制水平，这表明Mimusops治疗可逆地抑制Parkes小鼠的精子发生和生育能力。此外，在治疗的男性中没有可检测到的毒性迹象。

BACKGROUND & AIMS: :The status of chromatin during spermatogenesis is dynamically regulated by specific histone codes or stage-specific histone changes. The functional links between such epigenetic regulation and proteins regulating meiosis are largely unknown. In mammals, genes encoded on the Y chromosome are thought to possess male-specific biological functions. While genes located within the azoospermia factor region (AZF) are known to be involved in spermatogenesis, the physiological function of individual genes is not known. SMCY is a gene mapped to the AZF, and in this report, we analyzed the function of SMCY protein during spermatogenesis. Biochemical identification of the proteins with which it interacted showed that SMCY formed a distinct complex with MSH5, a critical meiosis-regulatory protein in the human testicular germ cell line, NEC8. As anticipated, histone H3K4 demethylase activity was detected. Immunohistochemical analysis revealed the co-localization of SMCY with MSH5 at a specific stage of meiotic prophase progression during murine spermatogenesis. Our results suggest that SMCY may have a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein to condensed DNA.

背景与目标： ：精子发生过程中染色质的状态由特定的组蛋白编码或特定阶段的组蛋白变化动态调节。这种表观遗传调控与调节减数分裂的蛋白质之间的功能联系在很大程度上是未知的。在哺乳动物中，Y染色体上编码的基因被认为具有雄性特定的生物学功能。虽然已知无精子症因子区域（AZF）中的基因与精子发生有关，但单个基因的生理功能尚不清楚。 SMCY是定位到AZF的基因，在本报告中，我们分析了SMCY蛋白在精子发生过程中的功能。与其相互作用的蛋白质的生化鉴定表明SMCY与MSH5形成了独特的复合物，MSH5是人睾丸生殖细胞系NEC8中的关键减数分裂调节蛋白。如所预期的，检测到组蛋白H3K4脱甲基酶活性。免疫组织化学分析显示，SMCY和MSH5在小鼠精子发生过程中特定阶段的减数分裂前期共定位。我们的结果表明，SMCY可能通过募集减数分裂调节蛋白到浓缩的DNA中，作为组蛋白H3K4脱甲基酶具有男性特异性功能。

BACKGROUND & AIMS: :In order to clarify the mechanism of synergism between follicle-stimulatory hormone(FSH) and testosterone (T) in the hormonal regulation of spermatogenesis, we studied the effects of recombinant human FSH (rhFSH) on the induction of spermatogenesis by testosterone in congenitally gonadotropin-deficient hpg mice. Weanling (day 21) homozygous hpg mice were administered daily subcutaneous injections of 1, 5, or 10 IU of rhFSH alone or in combination with a subdermal testosterone implant until day 70 of age. Spermatogenesis was quantitated by stereological estimation of germ cell populations and Sertoli cells as well as measurement of diameter of seminiferous tubules and their lumina in perfusion-fixed testes and by counting homogenization-resistant condensed testicular spermatids. Recombinant human FSH alone increased the absolute numbers of spermatogonia (x3.5-fold) and spermatocytes (x3-fold) compared with untreated hpg mice but did not significantly increase Sertoli cell numbers or form any condensed spermatids or tubular lumen. Relative to Sertoli cell numbers, rhFSH alone increased populations of spermatogonia (x2-fold) and spermatocytes (x2-fold). The addition of T to rhFSH further increased the absolute numbers of spermatogonia (x5-fold) and spermatocytes (x3.5-fold) compared with untreated hpg mice as well as increasing tubular diameter and forming tubular lumina. In addition administration of T allowed the completion of spermatogenesis in the presence of intratesticular T levels that were approximately 2% of non-hpg controls. All effects of the FSH + T combination were however no greater than the effects of the equivalent dose of T alone. The present study therefore indicates that rhFSH alone increases proliferation of premeiotic spermatogenic cells but has no effect on the completion of spermiogenesis or on Sertoli cell maturation. Furthermore we were unable to identify any additive effects of FSH with T in the hormonal regulation of spermatogenesis in the hpg mouse. This suggests that FSH or T both may stimulate initial spermatogenic development, but only T can complete spermiogenesis.

背景与目标： ：为了阐明卵泡刺激激素（FSH）和睾丸激素（T）之间在增生激素调节中的协同作用，我们研究了重组人FSH（rhFSH）对先天性促性腺激素诱导睾丸激素生精的影响。缺陷的hpg小鼠。每天给断奶（第21天）纯合的hpg小鼠皮下注射1、5或10 IU rhFSH或与皮下睾丸激素植入物组合注射，直到70岁。通过对生殖细胞群体和支持细胞的体视学估计以及在灌注固定的睾丸中生精小管及其管腔的直径的测量以及通过计数抗均质性的浓缩睾丸精子来定量精子发生。与未经治疗的hpg小鼠相比，重组人FSH单独增加了精原细胞的绝对数量（x3.5倍）和精母细胞的绝对数量（x3倍），但并没有显着增加Sertoli细胞数量或形成任何精子或管状管腔。相对于Sertoli细胞数，单独的rhFSH会增加精原细胞（x2倍）和精母细胞（x2倍）的数量。与未治疗的hpg小鼠相比，向rhFSH中添加T进一步增加了精原细胞的绝对数量（x5倍）和精母细胞的绝对数量（x3.5倍），并且增加了肾小管的直径并形成了管状的管腔。另外，在睾丸内T水平的存在下，T的施用允许完成精子发生，该水平约为非hpg对照的2％。但是，FSH T组合的所有作用均不大于同等剂量的T的作用。因此，本研究表明，仅rhFSH可增加减数分裂前生精细胞的增殖，但对精子发生的完成或对支持细胞的成熟没有影响。此外，我们无法确定FSH与T在hpg小鼠精子发生激素调节中的任何累加作用。这表明FSH或T均可刺激最初的生精过程，但只有T才能完成生精。

BACKGROUND & AIMS: :The radioprotective action of a preparation from Hippophae rhamnoides berries RH-3, already reported to render >80% survival against whole body 10 Gy gamma irradiation, was further investigated with respect to the testicular system. RH-3 was administered to mice 30 min before gamma irradiation (5 and 10 Gy) and histological parameters such as testis weight, sperm count, frequency of abnormal sperm, repopulation index, stem cell survival index and seminiferous tubular diameter were assessed on the 35th day. RH-3 administration partially countered radiation induced reduction in testis weight, sperm count, repopulation index and stem cell survival index (p < 0.01). The increase in the frequency of abnormal sperm (15.17 +/- 1.046%) caused by irradiation (5 Gy) was counteracted by pre-irradiation treatment with RH-3, which significantly decreased the level of abnormal spermatozoa to 7.99 +/- 0.918% (p < 0.001), i.e. 52% abnormalities in comparison with 5 Gy irradiated group. RH-3 treatment alone did not elicit any toxic or adverse effect on the process of spermatogenesis. The present study suggests that RH-3 treatment protected spermatogenesis by enhancing the spermatogonial proliferation, enhancing the stem cell survival and reducing sperm abnormalities. The presence of polyphenolic flavonoids and tannins in the extract and the radical scavenging activity might be responsible for the radioprotective action of RH-3.

背景与目标： ：关于睾丸系统，进一步研究了沙棘浆果RH-3制剂的辐射防护作用，该制剂已报道其对全身10 Gyγ射线的存活率> 80％。在γ射线照射（5 Gy和10 Gy）前30分钟向小鼠施用RH-3，并在35日评估组织学参数，如睾丸重量，精子计数，精子异常频率，再填充指数，干细胞存活指数和生精小管直径。日。 RH-3给药部分抵消了辐射引起的睾丸重量，精子数量，再填充指数和干细胞存活指数的降低（p <0.01）。辐射（5 Gy）引起的异常精子频率增加（15.17 /-1.046％）被RH-3的预辐射处理所抵消，这使异常精子的水平显着降低至7.99 /-0.918％（p <0.001），即与5 Gy照射组相比，异常率为52％。单独使用RH-3处理不会对精子发生过程产生任何毒性或不利影响。本研究表明，RH-3处理可通过增强精原细胞的增殖，增强干细胞存活率和减少精子异常来保护精子发生。提取物中多酚类黄酮和单宁的存在以及自由基清除活性可能是RH-3辐射防护作用的原因。

BACKGROUND & AIMS: :Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli cells, we perform a Sertoli-specific conditional deletion of Rac1, which encodes a Rho GTPase required for apicobasal cell polarity. Rac1 conditional knockout adults exhibit spermatogenic arrest at the round spermatid stage, with severe disruption of Sertoli cell polarity, and show increased germline and Sertoli cell apoptosis. Thus, Sertoli Rac1 function is critical for the progression of spermatogenesis but, surprisingly, is dispensable for fetal testicular development, adult maintenance of undifferentiated spermatogonia, and meiotic entry. Our data indicate that Sertoli Rac1 function is required only for certain aspects of spermatogenesis and reveal that there are distinct requirements for cell polarity during cellular differentiation.

背景与目标： ：Sertoli细胞是睾丸生精小管的支持细胞，为精子发生提供了滋养的环境。成年的支持细胞呈极化状态，因此它们可以同时支持基础的早期生精细胞（例如，精原细胞）和顶端的晚期细胞（例如，精子）。为了测试破坏Sertoli细胞中细胞极性的后果，我们对Seracoli进行条件特异性的Rac1缺失，该缺失编码了Apobobasal细胞极性所需的Rho GTPase。 Rac1条件性基因敲除的成年人在圆形精子阶段表现出生精停滞，严重破坏了Sertoli细胞的极性，并显示出种系和Sertoli细胞凋亡的增加。因此，Sertoli Rac1功能对于精子发生的进展至关重要，但令人惊讶的是，对于胎儿睾丸发育，成人未分化的精原细胞的维持以及减数分裂的进入都是必不可少的。我们的数据表明Sertoli Rac1功能仅在精子发生的某些方面才是必需的，并且揭示在细胞分化过程中对细胞极性有不同的要求。

BACKGROUND & AIMS: :Diabetes mellitus in human and animal models has been correlated with low sperm count, testicular abnormalities, high levels of germ cell death, and oxidative stress. In this study, we focus on three questions: (1) Is germ cell apoptosis stage-specific in diabetic male rats? (2) Could ascorbic acid (AA) reverse oxidative and histological damage and restore testicular dysfunction? (3) Could AA treatment restore fertility parameters in diabetic rats? Adult Sprague-Dawley rats were divided into four groups: control, diabetic, control plus AA, and diabetic plus AA. Seminiferous tubules underwent severe histological damage, together with a change in frequency of some stages of the seminiferous cycle, and germ cell apoptosis was increased in a stage-dependent manner in diabetic rats. We found a significant decrease in testosterone and higher levels of lipid peroxidation in diabetic rats when compared with controls. A major finding was that AA reversed the histological damage and peroxidation levels to control levels in diabetic rats, but testosterone levels remained unchanged. The pregnancy rate was decreased in females that mated with diabetic rats and those treated with AA, but the litter size was only reduced in the second case. Interestingly, spermatozoa from diabetic and AA-treated rats showed reduced motility and hyperactivation, but only diabetic rats had higher levels of apoptosis when compared with controls. These results suggest that treatment with AA reverses testicular damage in diabetic rats but is insufficient to restore testosterone levels, sperm motility, and fertility in a rat model.

背景与目标： 人和动物模型中的糖尿病与精子数量低，睾丸异常，生殖细胞死亡水平高和氧化应激有关。在这项研究中，我们关注三个问题：（1）糖尿病雄性大鼠生殖细胞凋亡是否具有阶段特异性？ （2）抗坏血酸（AA）能逆转氧化和组织损伤并恢复睾丸功能障碍吗？ （3）AA治疗能恢复糖尿病大鼠的生育能力吗？将成年的Sprague-Dawley大鼠分为四组：对照组，糖尿病，对照组加AA和糖尿病加AA。曲细精管经历了严重的组织学损伤，并伴有曲细精循环某些阶段的频率变化，并且在糖尿病大鼠中生殖细胞凋亡以阶段依赖性的方式增加。我们发现与对照组相比，糖尿病大鼠睾丸激素显着降低，脂质过氧化水平更高。一个主要发现是，AA使糖尿病大鼠的组织学损伤和过氧化水平逆转至对照水平，但睾丸激素水平保持不变。与糖尿病大鼠交配的雌性和接受AA治疗的雌性，其妊娠率降低，但仅在第二种情况下，其产仔数减少。有趣的是，来自糖尿病和AA治疗的大鼠的精子显示出降低的运动性和过度激活，但是与对照组相比，只有糖尿病大鼠具有更高的细胞凋亡水平。这些结果表明，AA治疗可以逆转糖尿病大鼠的睾丸损伤，但不足以恢复大鼠模型中的睾丸激素水平，精子活动性和受精能力。

BACKGROUND & AIMS: :Maintaining the integrity of spermatogenic stem cells is essential to transfer genetic information to a descendant. However, knowledge of maintenance of genetic stability in stem cells is still limited. RAD18 is critical for postreplication repair through mono- and multi-ubiquitination of proliferating cell nuclear antigen (PCNA) to maintain genomic stability. Mammalian RAD18 is highly expressed in the spermatocytes and the nuclei of a few spermatogonia in adult mice. To elucidate the physiological function of RAD18, we analyzed a phenotype of Rad18-/- mice. The mice were born and appeared to grow normally. Although the mice were fertile, fertility and testis weight decreased with age. Histological examination revealed normal spermatogenesis in almost all seminiferous tubules in Rad18-/- testes at 2 months old, and abnormal sperm could not be detected in the epididymis. However, 25% of the tubules lost almost all germ cells at 12 months. The seminiferous tubules frequently retained only late differentiated phase germ cells, suggesting that the exhaustion of spermatogonial stem cells leads to the loss of all germ cells in the seminiferous tubules. Wild-type germ cells were successfully transplanted into and colonized in the seminiferous tubules of aged Rad18-/- mice, indicating that Sertoli cells have a normal supportive function even in aged testes. We conclude that RAD18 is intrinsically required for the long-term maintenance of spermatogenesis.

背景与目标： ：维持生精干细胞的完整性对于将遗传信息传递给后代至关重要。但是，维持干细胞遗传稳定性的知识仍然有限。 RAD18通过增殖细胞核抗原（PCNA）的单泛素化和多泛素化来维持基因组稳定性，对于复制后修复至关重要。哺乳动物RAD18在成年小鼠的精细胞和少数精原细胞的核中高度表达。为了阐明RAD18的生理功能，我们分析了Rad18-/-小鼠的表型。小鼠出生并且看上去正常生长。尽管小鼠具有生育能力，但其生育力和睾丸重量会随着年龄的增长而下降。组织学检查显示，在两个月大的Rad18-/-睾丸中，几乎所有曲细精管中的精子发生均正常，并且在附睾中未检测到异常的精子。但是，在12个月时，有25％的肾小管几乎失去了所有生殖细胞。曲细精管经常仅保留晚期分化期的生殖细胞，这表明精原干细胞的耗尽导致了曲细精管中所有生殖细胞的丢失。野生型生殖细胞已成功移植到老年Rad18-/-小鼠的生精小管中并在其中繁殖，这表明Sertoli细胞即使在老年睾丸中也具有正常的支持功能。我们得出结论，RAD18是精子发生长期维持的内在要求。

BACKGROUND & AIMS: BACKGROUND:Histone to protamine exchange, in man, is only 80% complete and spermatozoal histones are highly acetylated suggesting that their associated genes may be involved in early gene expression in the embryo. METHODS:Using in situ hybridization and immunocytochemistry, we analyzed expression of protamine-1 and protamine-2, and histone H4 specifically acetylated at lysine 5 (H4K5ac), 8 (H4K8ac), 12 (H4K12ac) and 16 (H4K16ac) in human (n = 22) and marmoset (n = 6) testes and ejaculates. RESULTS:Protamine-1 and protamine-2 mRNA was present in round and elongating spermatids. All antibodies against acetylated histones revealed positive signals in these cells. Human spermatogonia showed positive signals for H4K8ac and H4K16ac, whereas marmoset spermatogonia were positive for H4K8ac and H4K12ac. In man, H4K16ac already displayed a positive immunoreaction with pachytene spermatocytes, starting at stage III of the seminiferous epithelial cycle. All antibodies showed positive immunostaining in ejaculated spermatozoa of both species. CONCLUSIONS:The common marmoset represents a suitable animal model for studies on nuclear protein expression during human spermatogenesis. The two species exhibit a similar organization of seminiferous epithelium and an identical expression pattern of protamine-1 and protamine-2 mRNA in round and elongating spermatids. The presence of specifically acetylated histones H4 in testicular spermatids and ejaculated spermatozoa demonstrates an incomplete histone to protamine exchange in both species. As acetylated histones are known to be associated with genes involved in gene expression, the common marmoset may, in future, be used as a model for investigations on early embryo development which, in man, are not possible for ethical reasons.

背景与目标： 背景：在人类中，组蛋白与鱼精蛋白的交换仅完成了80％，精子组蛋白高度乙酰化，表明它们的相关基因可能参与了胚胎的早期基因表达。
方法：使用原位杂交和免疫细胞化学技术，分析人（ n = 22）和mar（n = 6）睾丸和射精。
结果：在精子和圆形精子中都存在鱼精蛋白1和鱼精蛋白2的mRNA。所有针对乙酰化组蛋白的抗体在这些细胞中均显示阳性信号。人精原细胞对H4K8ac和H4K16ac呈阳性信号，而mar猴精原细胞对H4K8ac和H4K12ac呈阳性信号。在人类中，H4K16ac从生精上皮细胞周期的第III阶段开始就已经显示出与粗精子细胞的阳性免疫反应。所有抗体在两个物种的射精精子中均显示阳性免疫染色。
结论：普通mar猴是研究人类精子发生过程中核蛋白表达的合适动物模型。这两个物种的生精上皮组织相似，在圆形和延伸的精子细胞中，鱼精蛋白-1和鱼精蛋白2 mRNA的表达模式相同。睾丸精子和射精的精子中特异乙酰化组蛋白H4的存在表明这两种物种中鱼精蛋白交换的组蛋白不完全。由于已知乙酰化的组蛋白与参与基因表达的基因有关，因此普通mar猴将来可能被用作研究早期胚胎发育的模型，而在人类中，出于伦理原因，这是不可能的。

BACKGROUND & AIMS: :Exposure of male rats to cyclophosphamide, a commonly used anticancer and immunosuppressive drug, has been shown to alter fertility and progeny outcome in a male germ cell phase-specific manner. The effect of toxicant exposure on male germ cells depends in part on the stress response mechanisms present during the different stages of spermatogenesis. To assess how acute cyclophosphamide exposure affects the expression of stress response genes, we examined the expression of 216 genes, using gene expression arrays, in isolated rat spermatogenic cell types (pachytene spermatocytes, round spermatids, and elongating spermatids). Cyclophosphamide exposure affected gene expression in all cell types but most dramatically in round spermatids. Increased transcript levels were observed for 30 genes in round spermatids compared to seven genes in pachytene spermatocytes and two in elongating spermatids. The expression of genes involved in apoptosis, DNA-damage recognition and repair, transcriptional activation, and in the heat shock protein-chaperone response was most affected by cyclophosphamide in round spermatids. Our results demonstrate that cyclophosphamide alters the expression of stress response genes during spermatogenesis in a germ cell-specific manner. The greater response of round spermatids to cyclophosphamide suggests that this cell type may be more susceptible to the damaging effects induced by this drug, possibly due to the chromatin remodeling that is taking place at this stage of spermatogenesis. This observation is consistent with the reported higher level of abnormal progeny outcome seen when the germ cells were first exposed to cyclophosphamide as round spermatids.

背景与目标： ：雄性大鼠接触环磷酰胺是一种常用的抗癌和免疫抑制药物，已显示出以雄性生殖细胞阶段特异性的方式改变生育力和后代结局。有毒物质对雄性生殖细胞的影响部分取决于在精子发生不同阶段存在的应激反应机制。为了评估急性环磷酰胺暴露如何影响应激反应基因的表达，我们使用基因表达阵列检查了分离的大鼠生精细胞类型（粗大精细胞，圆形精细胞和伸长精细胞）中216个基因的表达。环磷酰胺暴露会影响所有细胞类型中的基因表达，但在圆形精子细胞中最显着。圆形精子中的30个基因的转录水平增加，而粗线精子细胞中的7个基因和伸长精子中的2个基因的转录水平增加。圆形精子中环磷酰胺对细胞凋亡，DNA损伤识别和修复，转录激活以及热休克蛋白-伴侣应答中涉及的基因表达的影响最大。我们的结果表明，环磷酰胺以生殖细胞特异性方式改变了精子发生过程中应激反应基因的表达。圆形精子对环磷酰胺的更大反应表明，这种细胞类型可能更容易受到这种药物诱导的破坏作用的影响，这可能是由于在精子发生这一阶段发生的染色质重塑。该观察结果与报告的较高水平的异常子代结局水平相一致，这是当生殖细胞首次以圆形精子细胞暴露于环磷酰胺时看到的。

BACKGROUND & AIMS: :The Azoospermia Factor c (AZFc) region on the Y chromosome long arm is one of the least stable regions in the human genome. It consists almost entirely of very long repeats and is prone to rearrangement. Numerous structures at AZFc have been identified, and some of them have been reported to be associated with male infertility. We screened 580 Han Chinese in Taiwan for AZFc deletion and duplication using three PCR assays, and characterized the DAZ genes in selected subjects with additional Southern analyses. About 9.5% of our subjects have AZFc partial deletion, 2.8% have partial deletion followed by duplication, and 1.7% have partial duplication. The overall rearrangement frequencies vary significantly between different Y chromosome haplogroups (Yhgs), ranging from 2.9% in O3e to 100% in N and Q. All individuals in Yhg-N lack the sY1191 marker, but one out of three of them actually have four DAZ genes, indicating further duplication after the b2/b3 deletion. Our additional screening of 142 oligospermic men and 107 fertile controls found no significant difference in the frequencies of the gr/gr and the b2/b3 deletion. However, the frequency of AZFc partial duplication in the infertile group (7.0%) was significantly higher than that in the fertile control group (0.9%) and the general Taiwanese population (1.7%). Our results indicate that AZFc partial deletion and partial duplication are common polymorphisms in Han Chinese, and that the AZFc partial duplication, but not the AZFc partial deletion, is a risk factor for male infertility in the Taiwanese population.

背景与目标： ：Y染色体长臂上的无精子因子c（AZFc）区是人类基因组中最不稳定的区域之一。它几乎完全由很长的重复组成，容易重新排列。已经确定了AZFc的许多结构，并且据报道其中一些与男性不育有关。我们使用三种PCR分析方法筛选了580位中国台湾汉族人群中AZFc缺失和重复的情况，并通过额外的Southern分析对了选定受试者中的DAZ基因进行了表征。我们的受试者中约有9.5％的人有AZFc部分缺失，有2.8％的人部分缺失，然后重复，有1.7％的人有部分重复。在不同的Y染色体单倍组（Yhgs）之间，总体重排频率差异显着，范围从O3e的2.9％到N和Q的100％。Yhg-N中的所有个体都缺乏sY1191标记，但是其中三分之一实际上有四个DAZ基因，表明b2 / b3缺失后进一步重复。我们对142名少精症男性和107名受精对照男性进行了额外筛查，发现gr / gr和b2 / b3缺失的频率没有显着差异。然而，不育组中AZFc部分复制的频率（7.0％）显着高于可育对照组（0.9％）和台湾普通人群（1.7％）。我们的结果表明AZFc部分缺失和部分重复是汉族人的常见多态性，而AZFc部分重复而不是AZFc部分缺失是台湾人群男性不育的危险因素。

BACKGROUND & AIMS: :Exposure to bisphenol A (BPA) has been related to male reproductive disorders. Since this endocrine disruptor also displays genotoxic and epigenotoxic effects, it likely alters the spermatogenesis, a process in which both hormones and chromatin remodeling play crucial roles. The hypothesis of this work is that BPA impairs early embryo development by modifying the spermatic genetic and epigenetic information. Zebrafish males were exposed to 100 and 2000 μg/L BPA during early spermatogenesis and during the whole process. Genotoxic and epigenotoxic effects on spermatozoa (comet assay and immunocytochemistry) as well as progeny development (mortality, DNA repairing activity, apoptosis and epigenetic profile) were evaluated. Exposure to 100 µg/L BPA during mitosis slightly increased sperm chromatin fragmentation, enhancing DNA repairing activity in embryos. The rest of treatments promoted high levels of sperm DNA damage, triggering apoptosis in early embryo and severely impairing survival. Regarding epigenetics, histone acetylation (H3K9Ac and H3K27Ac) was similarly enhanced in spermatozoa and embryos from males exposed to all the treatments. Therefore, BPA male exposure jeopardizes embryonic survival and development due to the transmission of a paternal damaged genome and of a hyper-acetylated histone profile, both alterations depending on the dose of the toxicant and the temporal window of exposure.

背景与目标： ：双酚A（BPA）的暴露与男性生殖系统疾病有关。由于这种内分泌干扰物还具有遗传毒性和表观遗传毒性作用，因此它很可能改变了精子发生过程，在此过程中激素和染色质的重塑都起着至关重要的作用。这项工作的假设是，双酚A通过修饰精子遗传和表观遗传信息来损害早期胚胎发育。斑马鱼的雄性在早期生精过程中和整个过程中都暴露于100和2000μg/ L BPA。评估了对精子的遗传毒性和表观遗传毒性作用（彗星试验和免疫细胞化学）以及子代发育（死亡率，DNA修复活性，细胞凋亡和表观遗传特征）。有丝分裂期间暴露于100μg/ L BPA会稍微增加精子染色质的碎片，从而增强胚胎中的DNA修复活性。其余的治疗促进了高水平的精子DNA损伤，触发了早期胚胎中的细胞凋亡，并严重损害了存活率。关于表观遗传学，在接受所有治疗的雄性精子和胚胎中，组蛋白乙酰化（H3K9Ac和H3K27Ac）同样得到增强。因此，由于父本受损基因组和高乙酰化组蛋白谱的传递，BPA男性暴露危害胚胎存活和发育，这两种改变均取决于毒物的剂量和暴露的时间窗。

BACKGROUND & AIMS: STUDY QUESTION:What is the consequence of Tex19.1 gene deletion in mice? SUMMARY ANSWER:The Tex19.1 gene is important in spermatogenesis and placenta-supported development. WHAT IS KNOWN ALREADY:Tex19.1 is expressed in embryonic stem (ES) cells, primordial germ cells (PGCs), placenta and adult gonads. Its invalidation in mice leads to a variable impairment in spermatogenesis and reduction of perinatal survival. STUDY DESIGN, SIZE, DURATION:We generated knock-out mice and ES cells and compared them with wild-type counterparts. The phenotype of the Tex19.1 knock-out mouse line was investigated during embryogenesis, fetal development and placentation as well as during adulthood. PARTICIPANTS/MATERIALS, SETTING, METHODS:We used a mouse model system to generate a mutant mouse line in which the Tex19.1 gene was deleted in the germline. We performed an extensive analysis of Tex19.1-deficient ES cells and assessed their in vivo differentiation potential by generating chimeric mice after injection of the ES cells into wild-type blastocysts. For mutant animals, a morphological characterization was performed for testes and ovaries and placenta. Finally, we characterized semen parameters of mutant animals and performed real-time RT-PCR for expression levels of retrotransposons in mutant testes and ES cells. MAIN RESULTS AND THE ROLE OF CHANCE:While Tex19.1 is not essential in ES cells, our study points out that it is important for spermatogenesis and for placenta-supported development. Furthermore, we observed an overexpression of the class II LTR-retrotransposon MMERVK10C in Tex19.1-deficient ES cells and testes. LIMITATIONS, REASONS FOR CAUTION:The Tex19.1 knock-out phenotype is variable with testis morphology ranging from severely altered (in sterile males) to almost indistinguishable compared with the control counterparts (in fertile males). This variability in the testis phenotype subsequently hampered the molecular analysis of mutant testes. Furthermore, these results were obtained in the mouse, which has a second isoform (i.e. Tex19.2), while other mammals possess only one Tex19 (e.g. in humans). WIDER IMPLICATIONS OF THE FINDINGS:The fact that one gene has a role in both placentation and spermatogenesis might open new ways of studying human pathologies that might link male fertility impairment and placenta-related pregnancy disorders. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Santé et de la Recherche Médicale (INSERM) (Grant Avenir), the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche, the Université de Strasbourg, the Association Française contre les Myopathies (AFM) and the Fondation pour la Recherche Médicale (FRM) and Hôpitaux Universitaires de Strasbourg.The authors have nothing to disclose.

背景与目标： 研究问题：小鼠Tex19.1基因缺失的后果是什么？
总结答案：Tex19.1基因在精子发生和胎盘支持的发育中很重要。
Tex19.1已在胚胎干（ES）细胞，原始生殖细胞（PGC），胎盘和成年性腺中表达。其在小鼠中的无效导致精子发生的可变性损伤和围产期生存期的减少。
研究设计，大小和持续时间：我们产生了敲除小鼠和ES细胞，并将其与野生型小鼠进行了比较。 Tex19.1基因敲除小鼠系的表型在胚胎发生，胎儿发育和胎盘形成以及成年期间进行了调查。
参与者/材料，设置，方法：我们使用小鼠模型系统生成了一个突变小鼠系，其中在种系中删除了Tex19.1基因。我们对Tex19.1缺陷型ES细胞进行了广泛的分析，并在将ES细胞注射入野生型胚泡后生成了嵌合小鼠，从而评估了它们的体内分化潜能。对于突变动物，对睾丸，卵巢和胎盘进行了形态学表征。最后，我们表征了突变动物的精液参数，并对突变睾丸和ES细胞中反转录转座子的表达水平进行了实时RT-PCR。
主要结果和可能的作用：虽然Tex19.1在ES细胞中不是必需的，但我们的研究指出，它对精子发生和胎盘支持的发育很重要。此外，我们观察到在Tex19.1缺陷的ES细胞和睾丸中II类LTR-反转录转座子MMERVK10C的过表达。
局限性，引起注意的原因：Tex19.1基因敲除表型的睾丸形态可变，从严重改变（在不育雄性中）到与对照组相比（在可育雄性中）几乎无法区分。睾丸表型的这种可变性随后阻碍了突变睾丸的分子分析。此外，这些结果是在具有第二种亚型（即Tex19.2）的小鼠中获得的，而其他哺乳动物仅具有一个Tex19（例如在人类中）。
结果的更广泛含义：一个基因在胎盘发育和精子发生中均起作用的事实可能会为研究可能与男性生育力障碍和胎盘相关的妊娠疾病相关的人类病理学开辟新途径。
研究资金/竞争兴趣：这项工作得到了国家科学研究所中心（CNRS），国家卫生研究中心（INSERM）（格兰特·阿韦尼尔），教育部的支持。法国国家安全研究与研究中心，斯特拉斯堡大学，法国精神病防治协会（AFM）和法国医学研究基金会（FRM）和斯特拉斯堡大学图书馆。

BACKGROUND & AIMS: :The Wnt/β-catenin pathway participates in many important physiological events such as cell proliferation and differentiation in the male reproductive system. We found that Kinesin-2 motor KIF3A is highly expressed during spermatogenesis in Eriocheir sinensis; it may potentially promote the intracellular transport of cargoes in this process. However, only a few studies have focused on the relationship between KIF3A and the Wnt/β-catenin pathway in the male reproductive system of decapod crustaceans. In this study, we cloned and characterized the CDS of β-catenin in E. sinensis for the first time. Fluorescence in situ hybridization and immunofluorescence results showed the colocalization of Es-KIF3A and Es-β-catenin at the mRNA and the protein level respectively. To further explore the regulatory function of Es-KIF3A to the Wnt/β-catenin pathway, the es-kif3a was knocked down by double-stranded RNA (dsRNA) in vivo and in primary cultured cells in testes of E. sinensis. Results showed that the expression of es-β-catenin and es-dvl were decreased in the es-kif3a knockdown group. The protein expression level of Es-β-catenin was also reduced and the location of Es-β-catenin was changed from nucleus to cytoplasm in the late stage of spermatogenesis when es-kif3a was knocked down. Besides, the co-IP result demonstrated that Es-KIF3A could bind with Es-β-catenin. In summary, this study indicates that Es-KIF3A can positively regulate the Wnt/β-catenin pathway during spermatogenesis and Es-KIF3A can bind with Es-β-catenin to facilitate the nuclear translocation of Es-β-catenin.

背景与目标： Wnt /β-catenin途径参与许多重要的生理事件，例如男性生殖系统中的细胞增殖和分化。我们发现Kinosin-2电机KIF3A在中华绒螯蟹的精子发生过程中高度表达。它可能会在此过程中促进货物的细胞内运输。然而，只有很少的研究集中在十足纲甲壳纲雄性生殖系统中KIF3A与Wnt /β-catenin途径之间的关系上。在这项研究中，我们首次克隆和表征了中华绒螯蟹中β-catenin的CDS。荧光原位杂交和免疫荧光结果显示Es-KIF3A和Es-β-catenin在mRNA和蛋白水平上共定位。为了进一步探索Es-KIF3A对Wnt /β-catenin途径的调控功能，在体内和中华绒螯蟹的原代培养细胞中，通过双链RNA（dsRNA）敲除了es-kif3a。结果表明，在es-kif3a敲除组中，es-β-catenin和es-dvl的表达降低。当es-kif3a被击倒时，精子形成后期Es-β-catenin的蛋白表达水平也降低，Es-β-catenin的位置从细胞核改变为细胞质。另外，co-IP结果表明Es-KIF3A可以与Es-β-catenin结合。总之，这项研究表明，Es-KIF3A可以在精子发生过程中正调控Wnt /β-catenin途径，Es-KIF3A可以与Es-β-catenin结合，促进Es-β-catenin的核转运。

BACKGROUND & AIMS: :Formin is one of the two major classes of actin binding proteins (ABPs) with nucleation and polymerization activity. However, despite advances in our understanding of its biochemical activity, whether and how formins generate specific architecture of the actin cytoskeleton and function in a physiological context in vivo remain largely obscure. It is also unknown how actin filaments generated by formins interact with other ABPs in the cell. Here, we combine genetic manipulation of formins mammalian diaphanous homolog1 (mDia1) and 3 (mDia3) with superresolution microscopy and single-molecule imaging, and show that the formins mDia1 and mDia3 are dominantly expressed in Sertoli cells of mouse seminiferous tubule and together generate a highly dynamic cortical filamentous actin (F-actin) meshwork that is continuous with the contractile actomyosin bundles. Loss of mDia1/3 impaired these F-actin architectures, induced ectopic noncontractile espin1-containing F-actin bundles, and disrupted Sertoli cell-germ cell interaction, resulting in impaired spermatogenesis. These results together demonstrate the previously unsuspected mDia-dependent regulatory mechanism of cortical F-actin that is indispensable for mammalian sperm development and male fertility.

背景与目标： ：Formin是具有成核和聚合活性的肌动蛋白结合蛋白（ABP）的两大类之一。然而，尽管我们对其生化活性的理解有了进步，但是在体内的生理情况下，福尔马林是否以及如何产生肌动蛋白细胞骨架的特定结构和功能仍不清楚。还不知道由福尔马林产生的肌动蛋白丝如何与细胞中的其他ABP相互作用。在这里，我们结合了formins哺乳动物透明的同系物1（mDia1）和3（mDia3）的基因操作与超分辨率显微镜和单分子成像，并显示formins mDia1和mDia3在小鼠曲细精管的Sertoli细胞中显性表达，并共同产生高度动态的皮质丝状肌动蛋白（F-actin）网状结构，与收缩性肌动蛋白束连续。 mDia1 / 3的丧失会破坏这些F-肌动蛋白的结构，诱导异位的非收缩性含espin1的F-肌动蛋白束，并破坏Sertoli细胞与生殖细胞的相互作用，从而导致精子发生受损。这些结果共同证明了皮质F-肌动蛋白的先前未曾怀疑的依赖mDia的调节机制，这对于哺乳动物的精子发育和雄性育性是必不可少的。

BACKGROUND & AIMS: -2

背景与目标： -2