Reviews of reproduction最新文献

Genetic maps provide a critical link between genes and phenotypes and are essential tools in the search for the genetic basis of variation in reproductive traits. Genes coding for hormones, growth factors, receptors, binding proteins, transcription factors and enzymes that influence the development and function of the reproductive axis have been assigned to genetic maps of ruminants and locations can be found in the respective genome databases. In addition, comparative information on gene structure and map location will help define the functions of essential genes. Gene locations from other species can be used because of extensive comparative links among mammalian gene maps. Large-scale projects to sequence genes and the ability to map these genes in parallel in radiation hybrid panels of different species will greatly improve the maps and our ability to translate between them. Cloning the genes responsible for genetic differences in fertility and fecundity in ruminants is likely to provide valuable clues to understanding ovarian function and germ cell development.

In cattle and other species, the corpus luteum plays a central role in the regulation of cyclicity and maintenance of pregnancy. In the absence of fertilization and implantation, the corpus luteum undergoes functional and morphological regression or luteolysis. Luteal regression is initiated in domestic ruminants by surges of prostaglandin F2alpha (PGF2alpha) from the uterus. Despite intensive investigation, the mechanisms by which PGF2alpha causes luteal regression remain undetermined. Recent studies from several laboratories have demonstrated that endothelial cells and their product, endothelin 1, are required for the manifestation of the luteolytic effects of PGF2alpha. Experimental evidence strongly supports the concept that luteal endothelin 1 inhibits luteal steroidogenesis and mediates the effects of PGF2alpha. Endothelin 1 caused a dose-dependent reduction in both basal and luteinizing hormone-stimulated biosynthesis of progesterone and prostacyclin, and an increase in PGF2alpha by ovine and bovine luteal cells. Specific receptors for endothelin 1 were identified on large and small bovine luteal cells, and the addition of specific endothelin receptor antagonists abolished the inhibitory effects of endothelin 1. Luteal endothelin 1 content increased as the cyclic corpus luteum aged, and the highest concentrations were observed during luteolysis. The amount of mRNA encoding endothelin 1 was greatly increased during the period of luteolysis. Gene expression for endothelin 1 was increased, in a time-dependent manner, in corpora lutea collected from heifers and ewes after exogenous administration of PGF2alpha. In heifers, exogenous PGF2alpha resulted in increased luteal output of endothelin 1. In ewes, the luteolytic effects of PGF2alpha were mitigated by pretreatment with a specific endothelin receptor antagonist. Administration of endothelin 1 or a sub-luteolytic dose of PGF2alpha to ewes reduced concentrations of jugular venous progesterone but did not shorten luteal lifespan. However, a combination of endothelin 1 and PGF2alpha acted synergistically to bring about complete luteolysis and reduced lifespan of the corpus luteum. In summary, endothelin 1 appears to have a direct effect on luteal cells in cattle and sheep, and it plays an essential role in mediating the luteolytic effects of PGF2alpha.

Placental tissues from humans, rodents and farm animals contain leptin and its receptor. Leptin produced by the human placenta has the same size, charge and immunoreactivity as leptin produced by adipose tissue. However, the expression of human placental leptin appears to be regulated by a placenta-specific upstream enhancer. In this review the occurrence of leptin and its receptor in a range of species and placental types is described, and its significance during pregnancy discussed. Placental leptin contributes to the increase in maternal circulating concentrations of leptin during late pregnancy when it is likely to have an endocrine role in regulating maternal energy balance. Placental leptin may have angiogenic and immunomodulatory activities, which affect the placenta in an autocrine or paracrine manner. It also appears to affect fetal growth and development by binding to leptin receptors present in fetal organs.

Fifty years after the first successful cryopreservation of spermatozoa, the technique is an integral part of the cattle breeding industry but has failed to establish itself commercially in the production of other breeds of domestic livestock. New assessment techniques have shown that the ejaculate consists of a heterogeneous population of cells, which achieve their full fertility potential at different rates within the female tract and thus maximize the chances of a fertile spermatozoon successfully combining with an egg. It is becoming apparent that the freeze-thaw process results in a more homogeneous cell population, which may be functionally compromised. One aspect of sperm function that has been demonstrated to be affected by cryopreservation is the process of capacitation. Chlortetracycline staining has shown that frozen-thawed spermatozoa undergo an accelerated 'capacitation-like' process which has implications for their interaction with the female tract, ability to establish sperm reservoirs in vivo and hence for their life expectancy after insemination. In addition to heterogeneity within the ejaculate, there is increasing evidence for variation between individuals in the success of sperm freezing. Post-thaw sperm survival may be consistently poor for certain individual animals even though pre-freeze parameters appear normal. The mechanisms that may underlie such differences in cryosensitivity remain unclear. A greater role for the use of frozen semen in livestock production can come only from an improvement in the preservation of the functional competence of the cryopreserved spermatozoon after insemination into the female tract.

Cadherins are cell surface proteins that are directly involved in a wide variety of processes such as cell adhesion, cell sorting, cell survival, morphogenesis, formation of intercellular junctions, maintenance of tissue integrity and tumourigenesis. This review discusses the multiple functions of cadherins in reproductive tissues. Furthermore, the role of the intracellular signalling protein beta-catenin in regulating cadherin function is reviewed. Finally, the findings that cadherin concentrations in reproductive tissues are responsive to steroid hormones is discussed. The modulation of cadherin expression by hormones is in agreement with the hypothesis that these proteins are dynamically involved in the maintenance of structure and function in reproductive tissues.

Binding to the zona pellucida of an egg stimulates the spermatozoon to undergo the acrosome reaction, a process that enables it to penetrate the egg. Before this binding, the spermatozoon undergoes a series of biochemical transformations in the female reproductive tract, collectively called capacitation. Only capacitated spermatozoa can bind to the zona pellucida and undergo the acrosome reaction. Protein kinases may be involved in the regulation of intracellular Ca2+ during capacitation and the acrosome reaction. The first event in capacitation is the increase in intracellular calcium, bicarbonate and hydrogen peroxide, which collectively activate adenylyl cyclase to produce cyclic AMP, which activates protein kinase A to phosphorylate certain proteins. During capacitation, there is an increase in membrane-bound phospholipase C, and this binding is highly stimulated by the addition of epidermal growth factor to the cells. The capacitated spermatozoon binds to the zona pellucida of the egg via specific receptors and it is suggested that the zona pellucida binds to at least two different receptors in the sperm head plasma membrane. One is a Gi-coupled receptor that can activate phospholipase Cbeta1 and may regulate adenylyl cyclase to further increase cyclic AMP concentrations. The cyclic AMP activates protein kinase A to open a calcium channel in the outer acrosomal membrane, resulting in a relatively small increase in cytosolic calcium. This increase in Ca2+ leads to activation of phospholipase Cgamma, which is coupled to the second tyrosine kinase receptor. The products of phosphatidyl-inositol bisphosphate hydrolysis by phospholipase C, diacylglycerol and inositol-trisphosphate, induce the activation of protein kinase C and a calcium channel in the outer acrosomal membrane, respectively. Protein kinase C opens a calcium channel in the plasma membrane and, together with the inositol-trisphosphate-activated calcium channel, leads to a second and higher increase in cytosolic calcium. In addition, the depletion of calcium in the acrosome activates a capacitative calcium entry mechanism in the plasma membrane, leading to a rapid increase in cytosolic calcium (300-500 nmol l(-1)). This increase in intracellular calcium concentration (and pH) leads to membrane fusion and the acrosome reaction.

There are two steroid 5alpha-reductase isoenzymes, designated type 1 and type 2, in mammals and recent experiments show that each plays a unique physiological role. In this article, the hypothesis is developed that the type 1 gene specifies a female isoenzyme, whereas the type 2 gene specifies a male isoenzyme. This idea results from the following observations. First, mutation of the 5alpha-reductase type 1 gene in mice affects reproduction in females by decreasing fecundity and blocking parturition, but has no effect on reproduction in males. Second, mutation of the 5alpha-reductase type 2 gene in mice and men prevents proper virilization but does not affect development or reproductive function in females. Analyses of these diverse phenotypes indicate that the isoenzymes catalyse both anabolic and catabolic reactions in steroid hormone metabolism.

Insulin-like growth factors and their binding proteins are key regulators of fetal and maternal tissue growth and development during human pregnancy. Insulin-like growth factors, particularly IGF-II, are produced in abundance by the trophoblast cells of the placenta, whereas one of the insulin-like growth factor binding proteins, IGFBP-1, is the major secretory product of the maternal decidualized endometrium. This spatial (and temporal expression) of the insulin-like growth factor axis infers a sophisticated paracrine regulatory mechanism for controlling insulin-like growth factor function. This paper reviews the potential roles of IGFBP-1 in human pregnancy by examining its effects on growth, metabolism and migration at the maternal-fetal interface and how these might be influenced by autocrine-paracrine post-translational modifications.

The gamete recognition and initial binding processes that are crucial for the success of mammalian fertilization are mediated by moieties associated with the extracellular matrix of the egg (the zona pellucida) and the head of the fertilizing spermatozoon. The zona proteins involved have been characterized in some detail, with ZP3 and ZP2 generally acknowledged to be responsible for the initial (primary) and secondary interactions, respectively. However, the identity of the complementary molecules on the sperm surface is highly contentious and remains unresolved. This review summarizes the current knowledge and controversies in this research area. The credentials of some of the major candidates and the probability of the involvement of multiple sperm receptors with different binding characteristics are assessed. Resolving this very important gap in our understanding is an essential prerequisite to understanding fully the molecular and signal transduction events that cause sperm acrosomal exocytosis. Such fundamental information is also imperative for the development of novel forms of contraception (or sterilization) targeted against specific sperm epitopes. Moreover, this information may contribute to our understanding of certain types of male infertility.