Reviews of reproduction最新文献

At fertilization of the mammalian egg, the spermatozoon initially binds to and then fuses with the egg plasma membrane. This critical event activates specific biochemical pathways within the egg. Activation of the egg induces resumption of meiosis and the start of rapid embryonic mitotic divisions on the one hand, and cortical granule exocytosis leading to modification of the zona pellucida and a block to polyspermy on the other. It has been shown in different systems that changes in intracellular ion concentrations can serve as second messengers of signal transduction mechanisms. The use of specific fluorescence probes, combined with the image analysis technique, facilitates the measurement of their dynamics in real time in the living cell and, thereby, assessment of their role in activation of the mammalian egg. This review focuses on the dynamics of intracellular Ca2+ and pH and their role in transducing the sperm signal to downstream cell cycle regulators.

The role of oxytocin in parturition is controversial. When considered as an endocrine hormone, the balance of evidence suggests that oxytocin has little involvement in the initiation of labour. However, recent research has demonstrated synthesis of mRNA encoding oxytocin within the pregnant human uterus. This article reviews the hypothesis that oxytocin is an important paracrine (or autocrine) hormone with respect to the control of myometrial contractility in late gestation. Experimental data are provided from humans when possible and from studies using the rat as an experimental model. The processing of oxytocin prohormones in uterine tissues is reviewed and the presence and possible role of carboxy-extended forms of oxytocin in late gestational tissues of rats are discussed. The regulation of oxytocin and its receptor, particularly by oestrogen and progesterone, is reviewed. The inter-relationship between oxytocin and prostaglandins is discussed. Finally, the metabolism of oxytocin within intrauterine tissues and the recent development of specific antagonistic analogues to oxytocin are considered. It is concluded that further clarification of this paracrine system within intrauterine tissues during late gestation could lead to more successful strategies for preventing or arresting preterm labour in women.

In many species, the timing of puberty is different in males and females. This does not simply reflect differences in the time course of activation of the testes and ovaries. Rather, sex differences in pubertal onset reside within brain mechanisms controlling GnRH secretion, as exemplified by studies conducted in sheep. Exposure of sheep fetuses to testicular steroids alters the timing of puberty, principally by reducing photoperiod responsiveness. This is manifest as an early increase in LH secretion in males or in females exposed experimentally to testosterone before birth. Steroids also act on non-photoperiodic mechanisms to abolish the preovulatory gonadotrophin surge. In view of these multiple organizational actions of steroids to control postnatal gonadotrophin secretion, it is becoming clear that there are many critical periods of brain development for organizing the GnRH neurosecretory system, and that these may be sensitive to different testosterone metabolites. Although GnRH neurones are not sexually dimorphic with respect to number, distribution or gross morphology, fundamental questions remain as to how steroids exert their effects at the cell through actions on GnRH afferents. Teleologically, these early sex-specific changes in mechanisms timing puberty maximize the chance that reproductive activity will ultimately be successful in each sex.

The heterodimeric glycoprotein hormone, human chorionic gonadotropin, has been extensively characterized in terms of its recognition by mouse monoclonal antibodies. A number of different approaches have led to the definition of several epitope clusters on the surface of the molecule. These include epitopes located solely on the alpha- or beta-chain, some of which are masked when the two chains associate to form the holo-hormone. Additional epitopes comprise amino acids contributed by both the chains. In contrast to the extensive knowledge regarding B cell epitopes, the characterization of T cell epitopes on hCG has only recently begun to be explored.

The inability of the embryo to utilize glucose as a fuel before compaction has been an area of much speculation. It is suggested that limitations in glucose transporter processes are the prime reasons for this. The recent identification of GLUT3 as the transporter responsible for the uptake of maternal glucose after compaction may provide the missing link in this puzzle. Furthermore, the coincidence of its expression with the onset of embryonic glucose utilization suggests that GLUT3 may be involved in the determination of metabolic priorities of the embryo. A model for the uptake of glucose by the blastocyst based on the function of two facilitative glucose transporters, GLUT3 and GLUT1, is proposed which can accommodate growth factor regulation of embryonic processes and is consistent with both the well established biochemical characteristics of GLUT proteins and the physiology of the embryo.

Sperm competition in birds occurs when a female is inseminated by more than one male during a single breeding cycle. Despite most birds being socially monogamous, sperm competition is widespread and results in frequent extra-pair paternity. Sperm competition is a fundamental part of sexual selection since it results in differential reproductive success among males. Male adaptations to sperm competition include relatively large testes, large sperm stores and long spermatozoa, mate guarding and frequent pair copulations. Females show no obvious morphological adaptations to sperm competition but, by controlling whether copulations are successful, they probably determine its frequency and extent. Despite this, the evolutionary benefits females acquire from extra-pair fertilizations are poorly understood. Experiments in which females are inseminated with equal numbers of spermatozoa from two males usually show last male sperm precedence. Understanding the mechanism of sperm competition requires understanding of why the last male to inseminate a female fertilizes a disproportionate number of eggs. The data from sperm competition studies on the domestic fowl, turkeys and zebra finches are consistent only with a passive sperm loss model of sperm competition. The mechanism is as follows: after insemination, spermatozoa enter the sperm storage tubules located in the oviduct, from which they are lost at a constant rate over days or weeks. All else being equal, the interval between two inseminations determines the probability of fertilization: the second of two inseminations fertilizes most eggs simply because, by the time fertilization occurs, fewer of these spermatozoa have been lost. Other factors also affect the outcome of sperm competition: the timing of insemination relative to oviposition, the differential fertilizing capacity of males and differences in the numbers of spermatozoa inseminated; as a consequence, last male sperm precedence is not automatic. On the basis of the mechanism of sperm competition, the optimal strategy for both males and females to maximize their likelihood of extra-pair fertilization is to copulate with an extra-pair partner as close as possible to the onset of oviposition.

It has been proposed that the steroidogenic acute regulatory (StAR) protein is the protein responsible for the acute regulation of steroid hormone biosynthesis. Virtually all of the observations made to date are consistent with this proposal. In this short review, background information leading to the discovery and characterization of the StAR protein and several recent and interesting observations concerning this protein are summarized.

Growth and ovulation of follicles, and development, maintenance, and regression of the corpus luteum depend on cyclical remodelling of the extracellular matrix. The extracellular matrix consists of proteinaceous and non-proteinaceous components and provides the tissue-specific, extracellular architecture to which cells attach, and modulates the activities of cells through cell surface receptors. Specific components of the extracellular matrix are cleaved by matrix metalloproteinases, the activities of which are inhibited by tissue inhibitors of metalloproteinases. This review presents evidence for the involvement of matrix metalloproteinases and their inhibitors in extracellular matrix remodelling associated with ovarian function.

There is strong evidence that cytokines and growth factors play an important role as local mediators of the actions of steroids on the endometrium to prepare it for implantation. These factors have also been shown to act in both an autocrine and paracrine manner to regulate the development of preimplantation embryos in several species. Attempts to define the function of each cytokine have involved receptor localization, establishment of the mode of control by steroid hormones, and functional assays in vivo and in vitro. However, because of the complex and redundant nature of cytokine networks, defining which of this plethora of factors plays a critical role in implantation has proved difficult. Although the development of preimplantation embryos can be influenced directly by cytokines, the in vitro culture of embryos from several species in defined media indicates that exogenous cytokines are not essential for development to the blastocyst stage. Nonetheless, supplementation of media with growth factors may prove valuable in overcoming the detrimental effects of embryo culture in vitro, which is widely used in assisted reproduction techniques in humans and domestic species. The creation of mouse strains in which specific genes for growth factors or adhesion molecules are deleted has also proved important in defining factors essential in implantation, as well as those that play a less significant role. Mice unable to express leukaemia inhibitory factor in the endometrium fail to support implantation, indicating a critical role for this protein in producing a receptive endometrium. Conversely, mouse embryos of the CF-1 strain, which lack the receptor for epidermal growth factor, fail to attach, indicating that this receptor is necessary for producing an implantation competent embryo. It is likely that abnormal expression of such receptors or their ligands in the endometrium underlies some forms of human infertility. Examining the actions of these factors in the endometrium will allow dissection of the molecular basis of embryo attachment and implantation.

The pineal hormone melatonin is secreted with a marked circadian rhythm. Normally, maximum production occurs during the dark phase of the day and the duration of secretion reflects the duration of the night. The changing profile of secretion as a function of daylength conveys photoperiodic information for the organization of seasonal rhythms in mammals. The role of melatonin in mammalian circadian physiology is less clear. However, exogenous melatonin can phase shift, and in some cases entrain, circadian rhythms in rodents and humans. It can also lower body temperature and induce transient sleepiness. These properties indicate that melatonin can be used therapeutically in circadian rhythm disorder. Successful outcomes have been reported, for example in jet lag and shift work, and with cyclic sleep disorder of some blind subjects. Melatonin receptors of several subtypes are found in the brain, the retina, the pituitary and elsewhere. They are currently under intense investigation. Melatonin agonists and antagonists are under development.