Reviews of reproduction最新文献

Intact reproductive development depends on steroids and other endocrine signals. Although recent discoveries have elucidated important steps of sexual differentiation, the intricate mechanisms that regulate the development of steroid-producing tissues remain elusive. In adults, complex feedback mechanisms determine the hypothalamic and pituitary regulation of steroid hormone biosynthesis. Steroidogenic factor 1 (SF-1), an orphan member of the nuclear receptor superfamily of proteins, plays a critical role in development and differentiation of the endocrine and reproductive systems. This review provides an overview of the function of SF-1, its mechanism of action, and a perspective on the interaction of SF-1 with other determinants of sexual differentiation. Whereas SF-1 is essential for the expression of numerous steroidogenic enzymes, its presence may not correlate with steroidogenic function. Moreover, diverse co-regulators modulate the influence of SF-1 on gene transcription. The significance of these interactions is discussed in the context of reproductive development and function. Other orphan or ligand-dependent nuclear proteins may share similar mechanisms.

Spermatogonial stem cell transplantation was first reported by Ralph Brinster's laboratory in 1994. It has proven to be a technological breakthrough in the study of both stem cells and Sertoli cell-germ cell interactions. This technique can be used to transfer testicular stem cells successfully from one animal to another of the same species (referred to as syngeneic transplants) and sometimes to an animal of a different species (xenogeneic transplants). This transfer technique, combined with developments in cryopreservation, long-term culture, and the enrichment of stem cell populations makes more significant breakthroughs likely in the near future. Ultimately, the application of spermatogonial stem cell transfer will allow transplantation of cultured stem cells manipulated genetically in vitro to give rise to functional male gametes with an altered genotype. This achievement will have applications in basic science, human medicine, and domestic and wild animal reproduction. Although progress toward this goal has been swift, potentially significant barriers, such as the stable incorporation of genetic material into stem cells and immunological responses to the introduced germ cells, remain to be overcome. This article is a review of the scientific advances made since the initial report of successful transplantation in 1994.

The receptor system and the molecular mechanisms by which inhibin acts on its target cells are poorly understood, in contrast to the situation for the structurally related molecule, activin. On the basis of evidence that the biological action of inhibin in a number of systems resembles that of an activin antagonist, it has been contended that inhibin operates by competition for the activin receptor rather than through a specific inhibin receptor. However, mounting evidence indicates that inhibin also interacts with high affinity and specificity with membrane-binding proteins that are likely to be the putative inhibin receptor.

The defining characteristic of mammals is that females nurse and care for their young; without this, the neonate has no chance to survive. Studies on wild and domestic species show that the neonatal period is the most critical step in the lifetime of a mammal. This review compares three well-studied species (the rabbit, pig and sheep) that differ in their parental strategies and in the problems that neonates have to overcome. As a general trend, mother-young interactions vary according to the maturity of the newborn, and the size of the litter. Neonatal survival relies to a great extent on an environment that is ecologically appropriate for the developmental stage of the neonate, and on optimum interactions with the mother. Adaptive maternal care supposes that the mother provides the basic needs of the neonate: warmth (in pigs and rabbits) or shelter, food, water and immunological protection (via colostrum) and, in some instances, protection from predators and other conspecifics. A major risk facing all neonates, other than the birth process itself, is inadequate colostrum intake owing to delayed suckling or competition with siblings, which leads to starvation, hypothermia or even crushing, as has been observed in pigs.

The uterine immune axis holds the key to solving major problems in female reproductive health, including infertility, many pathologies of pregnancy, and sexually transmitted disease. The molecular determinants of tolerance and immunity in the reproductive tract are now being identified, and the governing principles are similar to those in other mucosal tissues. Cytokines are implicated as pivotal regulators at important 'decision-making' points in each phase of the induction and elicitation of a response. Indeed, the flexibility to deal appropriately with antigens as disparate as infectious micro-organisms, spermatozoa and the conceptus is likely to be attributable to the sophistication of the cytokine network in driving immune deviation. A better understanding of the factors controlling the development of immune activity in the uterus, particularly the significance of the inductive cytokine environment in determining the destiny of T-lymphocyte responses, will assist the rational design of new therapeutic strategies to treat immune-based reproductive disorders.

Progesterone is synthesized in the peripheral nervous system in glial cells. The functions of progesterone are indicated by the findings that it stimulates neurite outgrowth from dorsal root ganglia sensory neurones in explant cultures, accelerates the maturation of the regenerating axons in cryolesioned sciatic nerve, and enhances the remyelination of regenerated nerve fibres. The formation of myelin sheaths around axons is a sexually dimorphic process, as the sheaths are thicker in female than in male regenerating nerves. The progesterone-induced myelination is probably mediated by progesterone receptors, as it is impaired by mifepristone (RU486), a progesterone antagonist. The stimulation of neurite growth in the peripheral nervous system may be mediated by a progesterone metabolite, 5alpha-tetrahydroprogesterone, through GABA(A) receptors.

Evidence from mouse mutants indicates that the Kit gene encoding KIT, a receptor present on the oocyte and theca cells, and the Mgf gene encoding KIT LIGAND, the ligand of KIT, are important regulators of oogenesis and folliculogenesis. Recently, in vitro cultures of fetal gonads, of follicles and of oocytes have identified specific targets for the KIT-KIT LIGAND interaction. In fetal gonads, an anti-apoptotic effect of KIT-KIT LIGAND interactions on primordial germ cells, oogonia and oocytes has been demonstrated. In postnatal ovaries, the initiation of follicular growth from the primordial pool and progression beyond the primary follicle stage appear to involve KIT-KIT LIGAND interactions. During early folliculogenesis, KIT together with KIT LIGAND controls oocyte growth and theca cell differentiation, and protects preantral follicles from apoptosis. Formation of an antral cavity requires a functional KIT-KIT LIGAND system. In large antral follicles, the KIT-KIT LIGAND interaction modulates the ability of the oocyte to undergo cytoplasmic maturation and helps to maximize thecal androgen output. Hence, many steps of oogenesis and folliculogenesis appear to be, at least in part, controlled by paracrine interactions between these two proteins.

Growth hormone (GH) is not classically considered as a reproductive hormone, although a vast literature indicates that it has roles in reproductive function. It is required for sexual differentiation and pubertal maturation and it participates in gonadal steroidogenesis, gametogenesis and ovulation. GH is also required for fetal nutrition and growth during pregnancy and for mammary development and lactation. Although some of these roles reflect the action of GH on the secretion and action of LH and FSH (Chandrashekar and Bartke, 1998), they also reflect direct actions of GH and indirect actions mediated through the local production of insulin-like growth factor I. Moreover, as GH is produced in gonadal and mammary tissues, these actions may reflect local autocrine or paracrine actions of extrapituitary GH, as well as the endocrine actions of pituitary GH. The roles of GH in reproductive function are considered in this review.

This review focuses on the importance of oestrogen and oestrogen receptors in the male reproductive system, with a special interest in the newly discovered role of oestrogen in the regulation of fluid reabsorption in the efferent ductules of the testis. Early work on oestrogen synthesis indicated that Leydig and Sertoli cells were the only important cells in the production of this steroid in the adult testis. However, more recent work has shown that germ cells and spermatozoa also contain aromatase and produce oestrogen. The observation that germ cells synthesize oestrogen contributed to a new hypothesis that oestrogen in the lumen of the male reproductive tract targets the epithelial lining of efferent ductules and the epididymis. The location of nuclear oestrogen receptors in the male reproductive tract has also been investigated and it has been found that oestrogen receptor alpha is more abundant in the efferent ductules of the testis than in any other tissue of the male or female. In all species examined to date, oestrogen receptor alpha has been found to be abundant in the efferent ductules. The structure and function of the efferent ductules are taken into account as these tubules are responsible for the reabsorption of almost 90% of the luminal rete testis fluid. Thus, it was logical to hypothesize that oestrogen receptors play a role in the regulation of fluid reabsorption in efferent ductules. The oestrogen receptor alpha knockout mouse was used to help define this role of the receptor in males. In this animal model, the efferent ductules are altered markedly from a reabsorptive epithelium to a squamous epithelium devoid of lysosomes and endocytotic organelles. Although the separate roles for oestrogens and androgens in the regulation of fluid reabsorption are controversial and remain to be resolved, it is now established that loss of oestrogen receptor function in males interferes with the resorptive function of efferent ductules, a function that is essential for fertility. Future studies will focus on the biochemical and physiological mechanisms involved in the regulation of water and ion movement by oestrogen in the male reproductive tract.

Oocyte quality in pigs is defined as the potential of that oocyte to develop into a viable offspring. There is increasing evidence that the programming of the oocyte must be completed before leaving the ovarian follicle, including both nuclear and cytoplasmic maturation. Pig oocytes matured in vitro under basic conditions are deficient in some, as yet unidentified, cytoplasmic factors and thus developmentally incompetent. This developmental incompetence can be overcome to some extent by follicular supplementation (with follicular fluid or granulosa cells) of the culture medium, emphasizing the importance of somatic signals during oocyte maturation. Furthermore, evidence is accumulating that the status of the follicle has a critical impact on the competence of the oocyte in vitro and in vivo and this has been demonstrated by co-culture with follicles at different maturational stages or from breeds with enhanced embryo survival. It now also appears that manipulation of maternal nutrition before mating or oocyte collection can enhance embryo survival in vivo and oocyte developmental competence in vitro, presumably by altering follicular secretions and hence the environment in which the oocyte is nurtured. Identification of both the key follicular factors influencing pig oocyte quality and reliable markers of oocyte quality will undoubtedly yield major improvements in embryo survival in vivo and embryo production in vitro.