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Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences. 应激对非啮齿动物生殖的影响:糖皮质激素和性别差异的作用。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050105
A J Tilbrook, A I Turner, I J Clarke

The means by which stress influences reproduction is not clearly understood, but may involve a number of endocrine, paracrine and neural systems. Stress impacts on the reproductive axis at the hypothalamus (to affect GnRH secretion) and the pituitary gland (to affect gonadotrophin secretion), with direct effects on the gonads being of less importance. Different stressors have different effects and there are differences in response to short- and long-term stress. Many short-term stresses fail to affect reproduction and there are reports of stimulatory effects of some 'stressors'. There are species differences in the way that specific stressors affect reproduction. Sex differences in the effects of a particular stressor have been delineated and these may relate to effects of stress at different levels of the hypothalamo-pituitary axis. The significance of stress-induced secretion of cortisol varies with species. In some instances, there appears to be little impact of short-term increases in cortisol concentrations and protracted increases in plasma concentration seem to be required before any deleterious effect on reproduction is apparent. Issues of sex, sex steroid status, type of stressor and duration of stress need to be considered to improve understanding of this issue.

压力影响生殖的方式尚不清楚,但可能涉及许多内分泌、旁分泌和神经系统。应激对下丘脑生殖轴(影响GnRH分泌)和垂体(影响促性腺激素分泌)的影响,对性腺的直接影响不太重要。不同的压力源有不同的影响,对短期和长期压力的反应也存在差异。许多短期压力不能影响生殖,而且有一些“压力源”的刺激作用的报告。在特定的压力源影响繁殖的方式上存在物种差异。在特定压力源的影响中,性别差异已经被描绘出来,这可能与压力在下丘脑-垂体轴的不同水平上的影响有关。应激诱导的皮质醇分泌的意义因物种而异。在某些情况下,皮质醇浓度的短期增加似乎没有什么影响,血浆浓度的长期增加似乎需要在对生殖产生任何有害影响之前出现。需要考虑性问题、性类固醇状态、应激源类型和应激持续时间,以提高对这一问题的理解。
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引用次数: 468
The zona pellucida: using molecular genetics to study the mammalian egg coat. 透明带:利用分子遗传学研究哺乳动物卵皮。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050114
T Rankin, J Dean

An extracellular matrix that mediates critical steps in fertilization and early development surrounds all vertebrate eggs. In mice and humans, this matrix is known as the zona pellucida and comprises three glycoproteins: ZP1, ZP2 and ZP3. Homologues of these proteins isolated from other vertebrates have conserved protein motifs that may be important for establishing a common fibrillar structure. However, specific but contradictory biological roles have been assigned to individual egg coat proteins based on assays in vitro in a wide range of species. Mouse lines lacking either ZP1 or ZP3 have been established with abnormal or absent zona matrices and varying degrees of infertility to examine zona structure and function in vivo. By crossing mouse lines lacking individual zona proteins with those expressing human homologues, the structural integrity of the zona matrix can be restored. Because mouse and human spermatozoa exhibit order-specific binding to the zona pellucida, mice with 'humanized' chimaeric zonae may provide an experimental system to elucidate the molecular basis of sperm-zona interaction.

在受精和早期发育的关键步骤中,细胞外基质包围着所有脊椎动物的卵。在小鼠和人类中,这种基质被称为透明带,由三种糖蛋白组成:ZP1, ZP2和ZP3。从其他脊椎动物中分离出的这些蛋白同源物具有保守的蛋白基序,这可能对建立共同的纤维结构很重要。然而,基于对多种物种的体外测定,已经确定了特定的但相互矛盾的生物学作用。我们建立了缺失ZP1或ZP3的小鼠细胞系,并建立了异常或缺失带基质和不同程度不育的小鼠细胞系,在体内检测带的结构和功能。通过将缺乏单个带蛋白的小鼠系与表达人类同源物的小鼠系杂交,可以恢复带基质的结构完整性。由于小鼠和人类精子与透明带具有顺序特异性结合,具有“人源化”嵌合带的小鼠可能为阐明精子与透明带相互作用的分子基础提供实验系统。
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引用次数: 69
Functional processing of fertilin: evidence for a critical role of proteolysis in sperm maturation and activation. 受精的功能加工:蛋白质水解在精子成熟和激活中的关键作用的证据。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050075
C P Blobel

Fertilin is a sperm surface protein with an essential role in fertilization. It is required for the migration of spermatozoa through the oviduct, for binding to the zona pellucida, and for efficient binding to the egg plasma membrane. Fertilin consists of two subunits, fertilin alpha and beta, both of which belong to the metalloprotease-disintegrin protein family (ADAMs). Fertilin alpha and beta are made as larger precursors that are processed proteolytically at different stages of sperm maturation in the testis and epididymis. Fertilin alpha is processed first, most likely by a pro-protein convertase in the secretory pathway of testicular cells. Fertilin beta is processed later, while spermatozoa are in transit through the epididymis. The processing of fertilin beta in the epididymis correlates with the acquisition of fertilization competence in spermatozoa, exposes an epitope that has a role in sperm-egg interactions, and triggers the relocalization of fertilin from the whole sperm head to the posterior head. These findings indicate that the proteolytic processing of fertilin and perhaps also other sperm proteins plays an important role in sperm maturation and activation in the epididymis. Further evaluation of the functional significance of proteolysis for sperm maturation should lead to new and exciting insights into the mechanism of sperm maturation, and may also uncover the cause of certain types of male infertility. The identification of the responsible proteases could provide novel targets for contraceptive drugs.

受精蛋白是精子表面的一种蛋白,在受精过程中起着重要作用。它是精子通过输卵管迁移、与透明带结合以及与卵质膜有效结合所必需的。肥料蛋白由α和β两个亚基组成,它们都属于金属蛋白酶分解蛋白家族(ADAMs)。在睾丸和附睾的精子成熟的不同阶段,α和β是作为较大的前体产生的。受精素α首先被处理,最有可能是由睾丸细胞分泌途径中的前蛋白转化酶处理。当精子在通过附睾的途中时,β -受精在稍后处理。附睾中受精β的加工与精子受精能力的获得相关,暴露了一个在精子-卵子相互作用中起作用的表位,并触发了精子从整个头到后头的再定位。这些发现表明,在附睾精子成熟和激活过程中,受精蛋白和其他精子蛋白的蛋白水解过程起着重要作用。进一步评估蛋白质水解对精子成熟的功能意义,将为精子成熟的机制带来新的和令人兴奋的见解,也可能揭示某些类型的男性不育的原因。对相关蛋白酶的鉴定可为避孕药物的开发提供新的靶点。
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引用次数: 67
Molecular mechanisms involved in the differentiation of spermatogenic stem cells. 生精干细胞分化的分子机制。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050093
K A Sutton

In male mammals, spermatogenesis proceeds for the reproductive lifetime of the animal. The continuation of this process depends upon a pool of spermatogenic stem cells within the testes that undergo asymmetric division to both maintain the stem cell population and give rise to progenitors that will proceed through spermatogenesis to generate mature spermatozoa. Thus, the development of functional spermatozoa may be divided into two distinct stages. The second, the process of spermatogenesis, is dependent upon the first, the successful formation of spermatogenic stem cells. Although spermatogenesis is characterized by marked cellular differentiation, the initial stages of germ line differentiation involve an avoidance of the differentiation signals acting during embryo development. The germ line is set aside early in embryo development and, while the primordial germ cells remain refractory to the differentiation signals affecting the soma, they undergo a number of phenotypic shifts before and after colonizing the genital ridge. Upon colonization of the genital ridge, the somatic tissue of the male genital ridge directs the final differentiation events that result in the formation of spermatogenic stem cells. It is this cell population that provides the basis for the maintenance of spermatogenesis in the adult.

在雄性哺乳动物中,精子的发生贯穿整个动物的生殖周期。这一过程的继续取决于睾丸内的生精干细胞库,这些干细胞进行不对称分裂,既维持干细胞群,又产生祖细胞,祖细胞将通过精子发生产生成熟的精子。因此,功能精子的发育可分为两个不同的阶段。第二个因素,即精子发生的过程,取决于第一个因素,即生精干细胞的成功形成。尽管精子发生的特点是显著的细胞分化,但生殖系分化的初始阶段涉及在胚胎发育过程中避免分化信号的作用。生殖系在胚胎发育早期被搁置一边,虽然原始生殖细胞仍然对影响体细胞的分化信号不敏感,但它们在定植生殖嵴之前和之后经历了许多表型变化。在生殖嵴定植后,雄性生殖嵴的体细胞组织指导最终分化事件,导致生精干细胞的形成。正是这种细胞群为维持成人精子发生提供了基础。
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引用次数: 16
Role of activins in the male reproductive tract. 激活素在男性生殖道中的作用。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050099
G P Risbridger, B Cancilla

The search for gonadal proteins that regulate pituitary FSH led to the isolation of inhibins and activins. As members of the transforming growth factor beta (TGFbeta) superfamily of growth and differentiation factors, these proteins have been shown subsequently to affect a range of tissues and systems beyond their role in reproduction. Studies on the expression and synthesis of activins in the male reproductive tract have localized these proteins in the testis, epididymis and prostate. In general, activins regulate cell proliferation and, consequently, the expression and localization of activin subunit mRNAs and proteins within these organs must be discrete. Activin ligand bioactivity is dependent on the presence of the appropriate receptors and signalling systems, but activin ligand formation or access to receptors is regulated by the formation of inhibins or by activin-binding proteins such as follistatin. This review examines the evidence that the capacity to synthesize activins and to regulate activin bioactivity resides in the cells of the male reproductive tract. It is concluded that activins exert their effects through local (autocrine or paracrine) mechanisms, rather than through endocrine systems. The interplay between the inhibins or follistatins provides a degree of regulation of activin bioactivity before ligand signalling events. The challenge for the future is to determine whether there is any difference between the action of individual activin ligands or whether these proteins are functionally redundant, indicating that compensatory mechanisms are essential for male reproductive tract function.

对调节垂体FSH的性腺蛋白的研究导致了抑制素和激活素的分离。作为转化生长因子β (tgfβ)生长和分化因子超家族的成员,这些蛋白随后被证明影响一系列组织和系统,而不仅仅是它们在生殖中的作用。对激活素在男性生殖道中的表达和合成的研究表明,这些蛋白定位于睾丸、附睾和前列腺。一般来说,激活素调节细胞增殖,因此,激活素亚基mrna和蛋白质在这些器官中的表达和定位必须是离散的。激活素配体的生物活性依赖于适当受体和信号系统的存在,但激活素配体的形成或受体的进入受抑制素的形成或激活素结合蛋白(如卵泡抑素)的调节。本文综述了男性生殖道细胞具有合成激活素和调节激活素生物活性的能力。结论是激活素通过局部(自分泌或旁分泌)机制发挥作用,而不是通过内分泌系统。抑制素或卵泡抑素之间的相互作用在配体信号事件之前提供了激活素生物活性的一定程度的调节。未来的挑战是确定单个激活素配体的作用之间是否存在任何差异,或者这些蛋白质是否在功能上是冗余的,这表明补偿机制对男性生殖道功能至关重要。
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引用次数: 34
Evolution of mammalian pregnancy in the presence of the maternal immune system. 在母体免疫系统存在下哺乳动物妊娠的进化。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050067
D R Bainbridge

Eutherian mammals have inherited a typical vertebrate immune system, which protects the body against infectious organisms by detecting and destroying foreign biological material. However, with the evolution of longer gestation periods, this protective mechanism became a potential threat to the 'semi-foreign' fetus and so eutherians have developed systems to prevent immune rejection of their developing fetuses. In many species, this is achieved by reducing placental expression of major histocompatibility complex (MHC) genes, the products of which are responsible for most transplantation rejection reactions. Unexpectedly, however, major histocompatibility complex expression is often re-established in the most invasive trophoblast cells. It is not known why transplantation antigen expression in the fetal cells most exposed to the maternal immune system is advantageous. It is possible that such expression aids the process of invasion or exerts an immunoprotective effect on the fetus. It may prove possible to identify the essential steps that all eutherian fetuses take to ensure their survival in the face of potential maternal immune attack by studying the common features of the placental immunology of different species.

真脊椎哺乳动物继承了典型的脊椎动物免疫系统,通过检测和破坏外来生物物质来保护身体免受传染性生物的侵害。然而,随着妊娠期的延长,这种保护机制成为对“半外来”胎儿的潜在威胁,因此真兽已经发展出了防止胎儿免疫排斥的系统。在许多物种中,这是通过减少胎盘主要组织相容性复合体(MHC)基因的表达来实现的,MHC基因的产物是大多数移植排斥反应的原因。然而,出乎意料的是,主要组织相容性复合体的表达经常在最具侵袭性的滋养细胞中重新建立。目前尚不清楚为什么在最暴露于母体免疫系统的胎儿细胞中移植抗原表达是有利的。这种表达可能有助于入侵过程或对胎儿施加免疫保护作用。通过研究不同物种胎盘免疫学的共同特征,有可能确定所有真动物胎儿在面对潜在的母体免疫攻击时为确保其生存所采取的基本步骤。
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引用次数: 91
Monocyte chemoattractant protein 1 in luteolysis. 单核细胞趋化蛋白1在黄体溶解中的作用。
Pub Date : 2000-05-01 DOI: 10.1530/ror.0.0050063
L A Penny

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokine family of cytokines which are involved in leukocyte physiology and trafficking. Interest in the role of inflammatory cells and their cytokine products in luteolysis has been increasing and there is mounting evidence demonstrating that MCP-1 is involved in luteolysis. Cell sources of MCP-1, such as endothelial cells, are abundant in late stage luteal tissue. Increased amounts of mRNA encoding MCP-1 are found after luteolysis in sheep, pigs, cows, rats and women and its up-regulation is associated with an increase in macrophages within the corpus luteum, indicating that MCP-1 may act as an inflammatory mediator during luteal regression. Luteolytic substances (prolactin in rats and prostaglandin F2alpha in ruminants) appear to be involved in increased expression of MCP-1 within the corpus luteum, although it is unclear whether this is a direct or indirect effect. Cytokines produced within the corpus luteum around luteolysis may also be involved in regulating MCP-1 expression. The field of chemokine biology is expanding rapidly and MCP-1, as well as other chemokines yet to be investigated, may prove to be an important link between the hormonal and cellular events within the corpus luteum around the time of luteolysis.

单核细胞趋化蛋白1 (MCP-1)是趋化因子家族的一员,参与白细胞的生理和运输。人们对炎症细胞及其细胞因子产物在黄体溶解中的作用越来越感兴趣,越来越多的证据表明MCP-1参与了黄体溶解。MCP-1的细胞来源,如内皮细胞,在晚期黄体组织中丰富。在羊、猪、牛、大鼠和女性的黄体溶解后发现编码MCP-1的mRNA数量增加,其上调与黄体内巨噬细胞的增加有关,表明MCP-1可能在黄体退化过程中起炎症介质的作用。黄体溶解物质(大鼠的催乳素和反刍动物的前列腺素f2 α)似乎与黄体中MCP-1的表达增加有关,尽管尚不清楚这是直接的还是间接的影响。黄体中产生的细胞因子也可能参与调节MCP-1的表达。趋化因子生物学领域正在迅速扩大,MCP-1以及其他尚未研究的趋化因子可能被证明是黄体体内激素和细胞事件之间的重要联系。
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引用次数: 76
The human corpus luteum: remodelling during luteolysis and maternal recognition of pregnancy. 人黄体:黄体溶解过程中的重塑和母体对妊娠的认识。
Pub Date : 2000-01-01 DOI: 10.1530/ror.0.0050012
W C Duncan

The marked tissue remodelling associated with luteolysis involves increased expression and activity of matrix metalloproteinases (MMPs) and an influx of immune cells, notably macrophages. Since the corpus luteum expresses high concentrations of specific tissue inhibitors of MMPs, it is clear that it is not only the increased activity of MMPs that is important, but also their tissue localization. Human chorionic gonadotrophin inhibits both MMP expression and macrophage influx in the rescued corpus luteum of early pregnancy. However, macrophages and the main cellular sources of MMPs in the corpus luteum do not express LH-hCG receptors. Therefore, it is likely that products of the steroidogenic cells, which do express LH-hCG receptors, are involved in the differential paracrine regulation of MMP expression and macrophage influx during luteolysis and maternal recognition of pregnancy.

与黄体溶解相关的显著组织重塑包括基质金属蛋白酶(MMPs)的表达和活性增加以及免疫细胞(尤其是巨噬细胞)的涌入。由于黄体表达高浓度的MMPs特异性组织抑制剂,很明显,重要的不仅是MMPs活性的增加,还有它们的组织定位。人绒毛膜促性腺激素抑制MMP表达和巨噬细胞内流在早期妊娠抢救黄体。然而,巨噬细胞和黄体中MMPs的主要细胞来源不表达hl - hcg受体。因此,甾体源性细胞的产物(表达hl - hcg受体)可能参与了黄体溶解和母体妊娠识别过程中MMP表达和巨噬细胞内流的差异旁分泌调节。
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引用次数: 95
Effects of dietary fatty acids on reproduction in ruminants. 饲粮脂肪酸对反刍动物繁殖的影响。
Pub Date : 2000-01-01 DOI: 10.1530/ror.0.0050038
R Mattos, C R Staples, W W Thatcher

Fats in the diet can influence reproduction positively by altering both ovarian follicle and corpus luteum function via improved energy status and by increasing precursors for the synthesis of reproductive hormones such as steroids and prostaglandins. Dietary fatty acids of the n-3 family reduce ovarian and endometrial synthesis of prostaglandin F2alpha, decrease ovulation rate in rats and delay parturition in sheep and humans. Polyunsaturated fatty acids such as linoleic, linolenic, eicosapentaenoic and docosahexaenoic acids may inhibit prostaglandin F2alpha synthesis through mechanisms such as decreased availability of its precursor arachidonic acid, an increased competition by these fatty acids with arachidonic acid for binding to prostaglandin H synthase, and inhibition of prostaglandin H synthase synthesis and activity. It is not known whether polyunsaturated fatty acids regulate expression of candidate genes such as phospholipase A2 and prostaglandin H synthase via activation of nuclear transcription factors such as peroxisome proliferator-activated receptors. Manipulation of the fatty acid profile of the diet can be used potentially to amplify suppression of uterine synthesis of prostaglandin F2alpha during early pregnancy in cattle, which may contribute to a reduction in embryonic mortality. Feeding fats and targeting of fatty acids to reproductive tissues may be a potential strategy to integrate nutrition and reproductive management to improve animal productivity.

饮食中的脂肪可以通过改善能量状态和增加合成生殖激素(如类固醇和前列腺素)的前体来改变卵巢卵泡和黄体功能,从而对生殖产生积极影响。n-3家族脂肪酸可降低卵巢和子宫内膜前列腺素f2 α的合成,降低大鼠的排卵率,延缓绵羊和人类的分娩。多不饱和脂肪酸如亚油酸、亚麻酸、二十碳五烯酸和二十二碳六烯酸可能抑制前列腺素f2 - α的合成,其机制包括降低其前体花生四烯酸的可用性,增加这些脂肪酸与花生四烯酸结合前列腺素H合成酶的竞争,抑制前列腺素H合成酶的合成和活性。目前尚不清楚多不饱和脂肪酸是否通过激活核转录因子如过氧化物酶体增殖物激活受体来调节候选基因如磷脂酶A2和前列腺素H合酶的表达。在牛的妊娠早期,通过控制饲粮中的脂肪酸分布,可以增强对子宫中前列腺素f2 α合成的抑制,这可能有助于降低胚胎死亡率。饲喂脂肪和以脂肪酸为目标的生殖组织可能是一种整合营养和生殖管理以提高动物生产力的潜在策略。
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引用次数: 401
Maternal recognition of pregnancy in marsupials. 有袋动物对怀孕的母体识别。
Pub Date : 2000-01-01 DOI: 10.1530/ror.0.0050006
M B Renfree
Pregnancy in kangaroos and wallabies (macropodid marsupials) induces multiple unilateral responses in the reproductive system that override those related to proximity to the single corpus luteum on one ovary or to the follicle on the contralateral ovary. This situation is in contrast to most other non-macropodid marsupials, in which the responses are dependent on the corpus luteum. There is now good evidence that these unilateral responses in macropodids are controlled by the feto-placental unit acting locally to stimulate the endometrium and myometrium. Pregnancy also influences the duration of the oestrous cycle and maternal behaviour. The stimuli responsible for these effects probably include paracrine, endocrine and mechanical stimuli resulting from uterine stretch. Taken together, these unilateral responses demonstrate that there is a refined maternal recognition of pregnancy in at least the macropodid marsupials.
袋鼠和小袋鼠(大足有袋类动物)的怀孕在生殖系统中引起多重单侧反应,这些反应超越了与靠近单个卵巢黄体或靠近对侧卵巢卵泡有关的反应。这种情况与大多数其他非大足类有袋动物相反,它们的反应依赖于黄体。现在有充分的证据表明,大足类动物的这些单侧反应是由胎儿-胎盘单位局部刺激子宫内膜和子宫肌层控制的。怀孕还会影响发情周期的持续时间和母亲的行为。造成这些影响的刺激可能包括旁分泌、内分泌和子宫拉伸引起的机械刺激。综上所述,这些单方面的反应表明,至少在大足类有袋动物中,母体对怀孕有一种精细的识别。
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引用次数: 47
期刊
Reviews of reproduction
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