Reviews of reproduction最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.