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Embryonic Modulation of Endometrial Receptivity 子宫内膜容受性的胚胎调节
Pub Date : 2018-10-01 DOI: 10.1274/jmor.35.53
Sakae Goto
Abstract: Implantation requires a receptive endometrium, a functionally normal embryo and communication between the developing embryo and maternal tissues (cross-talk). Two-step embryo transfer (two-step ET) and stimulation of endometrium embryo transfer (SEET) are procedures for ET based on concept of embryonic modulation of endometrial receptivity. In two-step ET, a cleaved embryo is transferred on day 2, and a blastocyst is transferred on day 5. The pregnancy and implantation rates with two-step ET were found to be higher than those with cleaved ET and double blastocyst transfer. We speculated that the cleaved embryos transferred on day 2 modulate endometrial receptivity and improve the implantation rate for blastocysts transferred on day 5. In SEET, embryo culture supernatant (ECS) is injected into the uterine cavity prior to blastocyst transfer to stimulate the endometrium and provide an optimum environment for implantation of forthcoming blastocysts. The pregnancy and implantation rates with SEET were found to be higher than those with blastocyst transfer. Higher implantation and pregnancy rates with SEET could be explained by embryonic factors produced in the culture medium that modulate endometrial receptivity. Lysophosphatidic acid was detected in ECS. Two-step ET and SEET are effective options for ET based on the concept of crosstalk between embryos and maternal tissues.
着床需要一个可接受的子宫内膜、一个功能正常的胚胎以及发育中的胚胎与母体组织之间的通信(串扰)。两步胚胎移植(Two-step embryo transfer,简称Two-step ET)和子宫内膜刺激胚胎移植(stimulation of endometrium embryo transfer,简称SEET)是基于胚胎调节子宫内膜容受性概念的胚胎移植程序。在两步体外受精中,在第2天移植一个卵裂胚胎,在第5天移植一个囊胚。两步体外受精的受孕率和着床率高于劈裂体外受精和双囊胚移植。我们推测第2天移植的卵裂胚胎调节子宫内膜容受性,提高第5天移植囊胚的着床率。在SEET中,胚胎培养上清(ECS)在囊胚移植前注入子宫腔,以刺激子宫内膜,为即将到来的囊胚着床提供最佳环境。SEET的妊娠和着床率高于囊胚移植。SEET患者较高的着床率和妊娠率可以解释为培养基中产生的调节子宫内膜容受性的胚胎因子。ECS检测溶血磷脂酸。基于胚胎与母体组织间串扰的概念,两步体外受精和单步体外受精是体外受精的有效选择。
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引用次数: 1
Expression of Genes Involved in the Non-Neuronal Cholinergic System and Their Possible Functions during Ovarian Follicular Development in Mice 小鼠卵巢卵泡发育过程中非神经元胆碱能系统相关基因的表达及其可能功能
Pub Date : 2018-10-01 DOI: 10.1274/jmor.35.61
Mizuki Ueno, Haruka Ito, Takuya Kanke, Yuta Matsuno, W. Fujii, K. Naito, K. Sugiura
Abstract: The regulatory roles of the non-neuronal cholinergic system, such as its growth promoting effects on mural granulosa cells during ovarian folliculogenesis, have been reported for several mammalian species; however, its roles in the early stages of follicles are not well-understood. This study was conducted to examine the expression of transcripts involved in the non-neuronal cholinergic system, and the effects of activating acetylcholine (ACh) signaling in mouse ovaries. The transcripts encoding proteins required in processes critical for ACh metabolism and a nicotinic cholinergic receptor, CHRNA7, were detected in ovaries and isolated mural granulosa cells. Stimulation with carbachol, a cholinergic agonist, promoted proliferation of mural granulosa cells in vitro. Moreover, carbachol treatment of neonatal ovaries significantly increased the numbers of primordial follicles compared with control untreated ovaries in organ cultures. These results suggest that a functional non-neuronal cholinergic system exists in mouse ovaries, and that it promotes the proliferation of mural granulosa cells and the formation/survival of primordial follicles.
摘要:非神经元胆碱能系统在卵巢卵泡形成过程中的调节作用,如对壁粒细胞的促生长作用,已经在几种哺乳动物中得到了报道;然而,它在卵泡早期阶段的作用尚不清楚。本研究旨在检测小鼠卵巢非神经元胆碱能系统相关转录本的表达,以及激活乙酰胆碱(ACh)信号的作用。在卵巢和分离的壁粒细胞中检测到编码乙酰胆碱代谢关键过程所需蛋白质和尼古丁胆碱能受体CHRNA7的转录本。胆碱能激动剂胆碱醇刺激可促进体外壁颗粒细胞的增殖。此外,在器官培养中,与未处理的对照卵巢相比,carbachol处理的新生儿卵巢显著增加了原始卵泡的数量。这些结果表明,小鼠卵巢中存在一个功能性的非神经元胆碱能系统,并促进壁粒细胞的增殖和原始卵泡的形成/存活。
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引用次数: 0
The Role of Phospholipase in Sperm Physiology and its Therapeutic Potential in Male Infertility 磷脂酶在精子生理中的作用及其在男性不育症中的治疗潜力
Pub Date : 2018-10-01 DOI: 10.1274/jmor.35.43
F. Kimura, K. Kishida, Chisako Horikawa, M. Izuno, Akiko Nakamura, Jun Kitazawa, Aina Morimune, Shoko Tsuji, A. Takebayashi, A. Takashima, S. Kaku, T. Murakami
Abstract: In mammals, the role of sperm in the process of fertilization is complex, and several well-defined steps must occur for the sperm to fertilize with the oocyte. Phospholipases (PLs), which regulate the lipid composition of the sperm by hydrolyzation of the phospholipids, are involved in the regulation of the flagellar beat, capacitation, and the acrosomal reaction, as well as in the triggering of the calcium oscillations in the oocyte that lead to oocyte activation. The emerging important role of phospholipases is also revealed by the fact that alterations of sperm lipids can lead to infertility. Phospholipases, especially PLCζ, could represent therapeutic targets to overcome male infertility.
摘要:在哺乳动物中,精子在受精过程中的作用是复杂的,精子与卵母细胞受精必须经过几个明确的步骤。磷脂酶(PLs)通过磷脂水解来调节精子的脂质组成,参与鞭毛跳动、获能和顶体反应的调节,以及触发卵母细胞内导致卵母细胞活化的钙振荡。磷脂酶的重要作用也在精子脂质的改变可导致不育的事实中得到揭示。磷脂酶,尤其是PLCζ,可能是克服男性不育的治疗靶点。
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引用次数: 0
Ovarian Stimulation in in vitro Fertilization 体外受精中的卵巢刺激
Pub Date : 2018-10-01 DOI: 10.1274/jmor.35.35
Y. Fukuda, Y. Katagiri, M. Morita
Abstract: In assisted reproductive technology (ART) treatments, the ovarian stimulation method is important for obtaining many good quality oocytes. The first ovarian stimulation treatments used high stimulation in long and short protocols with gonadotropin releasing hormone (GnRH) agonists. It was formulated to suppress the luteinizing hormone (LH) surge while the follicles are developing. Subsequently, a moderate stimulation with an antagonist was introduced following the development of GnRH antagonists, and low stimulation that inhibits the LH surge with continuous administration of clomiphene citrate. However, cases have been reported occurred in which estrogen replacement therapy was selected to facilitate follicular development by supplementing estrogen in ovarian insufficiency. Otherwise ART cryopreservation technology has also developed. These practices are referred to as oncofertility, and have given rise to new ovarian stimulation methods in infertility treatment. Ovarian stimulation with the random start or double stimulation methods, which are not readily affected by the menstrual cycle, and progestin-primed ovarian stimulation (PPOS) that inhibits the LH surge with a progestogen have come to be performed and are showing good outcomes. As the social and medical backgrounds change, the methods of ovarian stimulation may futher improve in the future.
摘要:在辅助生殖技术(ART)治疗中,卵巢刺激方法是获得大量优质卵母细胞的重要方法。第一次卵巢刺激治疗使用促性腺激素释放激素(GnRH)激动剂的长期和短期高刺激方案。它的配方是抑制黄体生成素(LH)激增,而卵泡正在发育。随后,随着GnRH拮抗剂的发展,引入了拮抗剂的中度刺激,以及通过持续施用克罗米芬抑制LH激增的低刺激。然而,有报道称,在卵巢功能不全的情况下,选择雌激素替代疗法通过补充雌激素来促进卵泡发育。此外,ART冷冻保存技术也得到了发展。这些做法被称为肿瘤生育,并已引起新的卵巢刺激方法在不孕症治疗。不受月经周期影响的随机启动或双重刺激卵巢的方法,以及用黄体酮抑制LH激增的黄体酮诱导卵巢刺激(PPOS)已被实施并显示出良好的效果。随着社会和医学背景的变化,卵巢刺激的方法在未来可能会进一步完善。
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引用次数: 0
Sex Steroid Hormones and Related Substances Involved in Primordial Follicle Activation 性类固醇激素及相关物质参与原始卵泡活化
Pub Date : 2018-05-02 DOI: 10.1274/jmor.35.3
F. Kimura, Luyi Zheng, Chisako Horikawa, Yuji Tanaka, Aina Morimune, T. Murakami
Abstract: Primordial follicles maintain dormancy in the ovary and only a small number of them are activated towards ovulation every day. Several signaling pathways in oocytes and the surrounding flattened pre-granulosa cells have been shown to play crucial roles in primordial follicle activations and sex steroid hormones are also known to affect it. Intrinsic estrogen, estradiol, has been reported to suppress primordial follicle formation and the later primordial follicle activation in rodent neonatal ovaries. Conversely, some phytoestrogens and endocrine disruptors which possess intrinsic estrogen-like biological activity with different binding affinities to estrogen receptors, can activate primordial follicles. Testosterone and dehydroepiandrosterone have been used in fertility treatments in the expectation that they would activate primordial follicle, although evidence of their efficacy is inconclusive. Progesterone suppresses primordial follicle formation and the later primordial follicle activation in rodent neonatal ovaries. Synthetic progestins possess the ability to bind to steroid hormone receptors other than the progesterone receptor. Thus, progestins may regulate primordial follicle activation through other sex hormone receptors. It may be possible to regulate primordial follicle activation by sex steroid hormones in the future. However, it is not yet clear which pathway mediates the effect of these hormones on primordial follicle activation, and this will need to be studied in the future.
摘要:原始卵泡在卵巢中处于休眠状态,每天只有少数卵泡被激活以排卵。卵母细胞和周围扁平的颗粒前细胞中的几种信号通路已被证明在原始卵泡激活中起关键作用,并且已知性类固醇激素也会影响它。据报道,雌性激素雌二醇抑制啮齿动物新生卵巢的原始卵泡形成和后期原始卵泡激活。相反,一些植物雌激素和内分泌干扰物具有内在的雌激素样生物活性,与雌激素受体的结合亲和力不同,可以激活原始卵泡。睾酮和脱氢表雄酮已被用于生育治疗,期望它们能激活原始卵泡,尽管其功效的证据尚无定论。黄体酮抑制啮齿动物新生卵巢原始卵泡形成和后期原始卵泡激活。合成孕激素具有与黄体酮受体以外的类固醇激素受体结合的能力。因此,孕激素可能通过其他性激素受体调节原始卵泡的激活。将来有可能通过性类固醇激素来调节原始卵泡的激活。然而,目前尚不清楚哪种途径介导这些激素对原始卵泡激活的影响,这需要在未来进行研究。
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引用次数: 0
The Regulation of Ovarian Follicular Growth by Anti-Müllerian Hormone 抗<s:1>勒氏激素对卵巢卵泡生长的调节作用
Pub Date : 2018-05-02 DOI: 10.1274/jmor.35.13
Tomoko Nakamura, Tomohiko Murase, S. Osuka, Maki Goto, A. Iwase
Abstract: Anti-Müllerian hormone (AMH) was originally discovered as the factor responsible for the regression of the Müllerian duct during male sexual differentiation. Through studies of AMH knockout mice, AMH has also been found to regulate primordial follicle recruitment and FSH-dependent cyclic recruitment. However, the details of how AMH influences follicular growth have not been elucidated. Since the early 2000s, when serum AMH concentration was found to be a reliable biochemical marker of ovarian reserve, AMH has been in the spotlight in reproductive medicine. Several studies of AMH have led to new insights on the mechanism of AMH-regulated follicular growth. Here, we review from the earliest studies to the latest findings, AMH regulation of follicle growth with reference to the potential clinical uses of AMH and AMH inhibitors.
摘要:抗勒氏管激素(anti - mlerian hormone, AMH)最初被发现是在雄性性分化过程中导致勒氏管退化的因素。通过对AMH敲除小鼠的研究,也发现AMH可以调节原始卵泡募集和fsh依赖性循环募集。然而,AMH如何影响卵泡生长的细节尚未阐明。自21世纪初,血清AMH浓度被发现是卵巢储备的可靠生化指标以来,AMH一直是生殖医学研究的焦点。对AMH的几项研究对AMH调节卵泡生长的机制有了新的认识。在这里,我们回顾了从最早的研究到最新的发现,AMH对卵泡生长的调节,并参考了AMH和AMH抑制剂的潜在临床应用。
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引用次数: 0
The Safety of Autotransplantation of Cryopreserved Ovarian Tissue in Cancer Patients 肿瘤患者自体冷冻卵巢组织移植的安全性
Pub Date : 2018-05-02 DOI: 10.1274/jmor.35.27
Y. Iwahara
Abstract: Aggressive chemotherapy and radiotherapy can cure cancer in young female patients, but they can also result in the loss of ovarian function. For these young survivors, both recovery of ovarian function and reproductive potential after treatment have become important quality of life issues. Ovarian tissue cryopreservation (OTC), followed by transplantation after cancer remission is the most commonly applied fertility restoration approach in prepubertal females and women who require immediate cancer therapy. A major concern of frozen-thawed ovarian tissues (FTOT) autotransplantation in cancer survivors is the reintroduction of malignant cells that may have metastasized to the graft. There are several detection methods for minimal residual diseases (MRD) in ovarian cortex tissues. The aim of this paper is to review the available data describing the safety of transplantation of FTOT from cancer patients, focusing on the methods used to detect tumor cells in ovarian tissues and future perspectives in this field.
摘要:积极的化疗和放疗可以治愈年轻女性患者的癌症,但也可能导致卵巢功能的丧失。对于这些年轻的幸存者来说,治疗后卵巢功能和生殖潜力的恢复已经成为重要的生活质量问题。卵巢组织冷冻保存(OTC),在癌症缓解后进行移植是青春期前女性和需要立即接受癌症治疗的女性最常用的生育恢复方法。冷冻解冻卵巢组织(FTOT)自体移植在癌症幸存者中的一个主要问题是可能已经转移到移植物的恶性细胞的重新引入。卵巢皮质组织微小残留病变(MRD)的检测方法有多种。本文的目的是回顾描述癌症患者FTOT移植安全性的现有数据,重点介绍用于检测卵巢组织中肿瘤细胞的方法以及该领域的未来展望。
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引用次数: 0
Histomorphological Aspects of the Ovarian Cortex Regarding Ovarian Reserve and Local Pelvic Inflammation 卵巢皮层与卵巢储备和局部盆腔炎的组织学关系
Pub Date : 2018-05-02 DOI: 10.1274/jmor.35.21
Michio Kitajima, Naoko Murakami, K. Taniguchi, Yuriko Kitajima, Ozora Tsukamoto, K. Miura, H. Masuzaki
Abstract: The ovaries of women of reproductive age may show specific histological structures that may relate to the maintenance of primordial follicles and the regulation of early follicular development, which are keys to understanding the dynamics of ovarian reserve. The pelvic environment of women is frequently exposed to physiological or pathological inflammatory stimuli. Endometriosis is a disorder that should be viewed as a chronic inflammatory disease manifested by pelvic pain and infertility. Inflammation surrounding the normal ovarian cortex may alter the histological structure which possesses primordial and early growing follicles. Fibrotic changes in histological niches in the nest of primordial follicles may provoke activation of dormant follicles and concomitant atresia. Along with decline in AMH, which is produced by early growing follicles, fibrotic changes may accelerate the demise of primordial follicles which has been described as “burn-out by inflammation”. As a result, women with endometriosis may suffer from diminished ovarian reserve, a possible cause of endometriosis-related infertility.
摘要:育龄妇女卵巢可能表现出与原始卵泡维持和早期卵泡发育调控有关的特殊组织学结构,这是了解卵巢储备动态的关键。女性盆腔环境经常受到生理性或病理性的炎症刺激。子宫内膜异位症是一种应被视为慢性炎症性疾病,表现为盆腔疼痛和不孕。正常卵巢皮层周围的炎症可改变具有原始和早期生长卵泡的组织学结构。原始卵泡巢中组织学壁龛的纤维化变化可能引起休眠卵泡的激活和伴随的闭锁。随着AMH(由早期生长的卵泡产生)的减少,纤维化的变化可能会加速原始卵泡的死亡,这被描述为“炎症燃烧”。因此,患有子宫内膜异位症的女性可能会遭受卵巢储备减少的痛苦,这可能是导致子宫内膜异位症相关不孕的原因。
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引用次数: 2
The Inability of Human Sperm with Chromosomal Abnormalities to Penetrate the Oocyte in Assisted Reproductive Technology (ART): Risk Factors and the Role of Seminal Plasma 辅助生殖技术(ART)中染色体异常的人类精子不能穿透卵母细胞:危险因素和精浆的作用
Pub Date : 2017-10-01 DOI: 10.1274/jmor.34.65
Seiji Watanabe, A. Fukui, Rika Nakamura, R. Fukuhara, Ayano Funamizu
Abstract: The combination of ICSI and a sperm chromosome assay provides a useful opportunity to directly investigate relationships between chromosomal aberrations and head morphology, motility or in vitro aging. An increase of aneuploidy was identified in sperm with large heads. Structural chromosome aberrations were frequently found in elongated heads. These types of sperm should therefore be avoided for ICSI and can easily be identified under a microscope. In sperm with normal heads, the chromosomal aberration rate was initially low but increased gradually after removal of the seminal plasma (3.3% to 15.9%); in immotile sperm, the increase of DNA damage was more pronounced (4.5% to 48.1%). Therefore, there are motile and immotile sperm populations in human ejaculates that are potentially vulnerable to in vitro culture conditions. Since these sperm can maintain DNA integrity in the seminal plasma for at least 3 h, and even after cryopreservation, the seminal plasma appears to be an efficient suppressor of DNA damage. We report here our attempts at using ICSI using sperm stored in the seminal plasma (SP-ICSI) to treat infertile patients with normozoospermia and provide data to confirm the safety of this technique. For poor quality semen, SP-ICSI may be more effective in achieving a successful outcome.
摘要:ICSI与精子染色体检测的结合为直接研究染色体畸变与头部形态、运动能力或体外衰老之间的关系提供了有益的机会。在头部较大的精子中发现了非整倍体的增加。结构染色体畸变常见于长头。因此,这些类型的精子应该避免进行ICSI,并且可以很容易地在显微镜下识别。在头部正常的精子中,染色体畸变率起初较低,但在去除精浆后逐渐升高(3.3% ~ 15.9%);在不动精子中,DNA损伤的增加更为明显(4.5%至48.1%)。因此,人类射精中有活动和不活动的精子群体,它们可能容易受到体外培养条件的影响。由于这些精子可以在精浆中保持DNA完整性至少3小时,甚至在冷冻保存后,精浆似乎是一种有效的DNA损伤抑制剂。我们在此报告了我们使用储存在精浆中的精子进行ICSI (SP-ICSI)治疗无精子症不孕患者的尝试,并提供了证实该技术安全性的数据。对于质量差的精液,SP-ICSI可能更有效地获得成功的结果。
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引用次数: 2
The Inflammatory Process and Successful Implantation 炎症过程和植入成功
Pub Date : 2017-10-01 DOI: 10.1274/jmor.34.75
F. Chishima, T. Nakajima, Takehiro Nakao, Chuyu Hayashi, G. Ichikawa, Atsushi Komatsu, K. Kawana
Abstract: Implantation is essential for successful reproduction. In humans, uterine receptivity is restricted to the mid-secretory phase, days 19 to 24 of the menstrual cycle; and this period is called the window of implantation (WOI). Large populations of decidual leukocytes infiltrate the implantation site, and the levels of cytokines, prostaglandins (PGs), and leukocytes are up-regulated in the endometrium during implantation. Implantation is like a local wound healing process which is characterized by a strong Th1, pro-inflammatory response in which high levels of pro-inflammatory cytokines such as IL-6, LIF, IL-8, and TNFα are involved. In addition, cyclooxygenase (COX)-2 expression increases between days 2 to 5, suggesting that PGs are necessary for the process of stromal cell decidualization in early pregnancy. Recently, it was reported that endometrial biopsies taken during spontaneous cycles that preceding IVF treatment improved the rate of implantation, clinical pregnancies, and live births in patients with recurrent implantation failure. These results suggest an ininflammatory environment is not adequately induced in some IVF patients with recurrent implantation failure in the absence of local injury provoked by biopsy treatment, further suggesting that uterine receptivity is mediated by the expression of molecules associated with a pro-inflammatory process.
摘要:着床是成功生殖的必要条件。在人类中,子宫接受性仅限于分泌中期,即月经周期的第19天至第24天;这一时期称为植入窗口(window of implantation, WOI)。大量的蜕膜白细胞浸润着床部位,细胞因子、前列腺素(pg)和白细胞水平在着床期间在子宫内膜上调。植入术类似于局部伤口愈合过程,其特征是强烈的Th1、促炎反应,其中高水平的促炎细胞因子如IL-6、LIF、IL-8和TNFα参与其中。此外,环氧化酶(COX)-2的表达在第2天至第5天增加,表明PGs在妊娠早期间质细胞脱胞过程中是必需的。最近有报道称,在IVF治疗前的自然周期内进行子宫内膜活检可提高复发性植入失败患者的着床率、临床妊娠率和活产率。这些结果表明,在没有活检治疗引起的局部损伤的情况下,一些复发性着床失败的IVF患者没有充分诱导炎症环境,进一步表明子宫接受性是由与促炎过程相关的分子表达介导的。
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引用次数: 1
期刊
Journal of mammalian ova research
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