New blood vessel growth is generally a rare event in the healthy adult. However, a notable exception to this is the female reproductive tract where cyclic angiogenesis occurs. Striking new vessel growth and remodeling also occurs during placentation; thus angiogenesis is essential for reproductive success. Vascular endothelial growth factor is a potent stimulator of this process and its production and action is tightly regulated. Indeed the placenta is a rich source of a soluble variant of the flt-1 receptor which seems to protect the placenta from the effects of excess vascular endothelial growth factor. The balance between new vessel growth (in the placental villi for example) and endothelial cell loss in the spiral arteries within the decidua is a delicate one. This is influenced by the local production of promotors and inhibitors of endothelial cell activation. Perturbation of this may lead to maternal pathology during pregnancy.
Journal Article Regulation of pituitary gonadotrophin gene expression Get access J.E. Mercer, J.E. Mercer Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute and Harvard Medical SchoolBoston, MA 02115, USA 1 Present address: Prince Henry's Institute of Medical Research, PO Box 152. Clayton 3168, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar W.W. Chin W.W. Chin 2 Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute and Harvard Medical SchoolBoston, MA 02115, USA 2 To Whom correspondence should be addressed. Tel: (617) 732 5856; Fax: (617) 732 5123 Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, Volume 1, Issue 4, 1995, Pages 363–384, https://doi.org/10.1093/humupd/1.4.363 Published: 01 July 1995
Journal Article The gonadotrophin-releasing hormone receptor: structural determinants and regulatory control Get access Stuart C. Sealfon, Stuart C. Sealfon 1 1Fishberg Research Center for Neurobiology and Department of Neurology, Mount Sinai School of MedicineNew York, NY 10029, USA To whom correspondence should be addressed. Telephone: (212) 241 7075; Fax: (212)996 9785 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert P. Millar Robert P. Millar Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction Update, Volume 1, Issue 3, 1 January 1995, Pages 216–230, https://doi.org/10.1093/humupd/1.3.216 Published: 01 May 1995
This article reviews recent research on autoimmune diseases of the testis and ovary based on two experimental approaches for induction of autoimmune diseases of the gonads (immunization with testis or ovary antigen, usually with adjuvant, and deliberate alteration of the immune system in normal animals, without injecting antigen or adjuvant). It has been found that the local testicular immunoregulatory environment partially impedes autoimmune responses to ontogenic testis antigens and regulatory T cells usually control pathogenic T cells that are found in the normal peripheral immune system. If the clonal balance of these CD4+ T cell subsets is tipped in favour of pathogenic T cells, autoimmune diseases of the gonads could ensue. Loss of regulatory T cells may occur through aberrant T cell development, or oophoritogenic T cells can be activated by non-ovarian peptides that crossreact with self peptides at the level of the T cell receptor. The inflammatory CD4 (Th1) T cell mechanism has been established to be a critical pathway for autoimmune orchitis and autoimmune oophoritis; tumour necrosis factor has been shown to be required for amplification of the pathogenic T cell response. Histopathology has suggested tissue locations wherein pathogenic T cells encounter testicular and ovarian target antigens. Antibodies bind to both testicular and ovarian target antigens during the development of autoimmune orchitis and autoimmune oophoritis, but the precise role of the antibodies has not been determined. Resolution of this role may influence the clarification of the mechanism whereby autoantibody may access ejaculated human spermatozoa to cause infertility and the future of contraceptive vaccine development based on ovarian antigens. A novel mechanism of autoantibody induction and an immunogenetic approach to autoimmune oophoritis and orchitis, based on molecular linkage analysis of inbred mice, are also reviewed.
It has been hypothesized for some time that secretions of the oviduct and uterus are involved in stimulating cell proliferation in preimplantation mammalian embryos and promotion of early differentiation events that lead to successful implantation. At least some of the regulatory factors present within uterine secretions are growth factors that can act along a paracrine pathway by binding to specific receptors on embryonic cells. A list of polypeptide growth factors present in uterine tissues and fluids has been previously published by Brigstock et al. (1989) and along with those reported in this review, includes EGF, TGF-alpha, insulin, IGF-I, IGF-II, IGF-BPs, acidic and basic FGF, and CSF-1. The early embryo itself produces a number of growth factors and receptors. A summary of those covered in this review, including temporal aspects of their expression, is contained in Table 2.1. Most of the data are from studies on mouse embryos but where, possible, we have also included reports for other mammalian embryos. Taken together with the factors present in oviduct and uterine secretions, it is clear that preimplantation embryos reside in an environmental milieu in which they are exposed to growth factors of many kinds and that regulatory pathways at the autocrine, juxtacrine, and paracrine levels may all be operating. From a functional point of view, many of the factors we have reviewed have been shown to be able to enhance development when added to medium for culture of preimplantation embryos. The exact circuit or pathway and mechanism through which they exert their effects remain, for the most part, to be elucidated. None the less, a number of general features regarding growth factor function during preimplantation development have emerged. There appears to be a redundancy of gene products within several growth factor families, all of which can stimulate cell proliferative or metabolic events when added exogenously to preimplantation embryos in culture. Perhaps, then, in addition to functions of growth factors acting singly on their specific receptors, combinations of factors are important for induction of a specific developmental response. We have included many examples of synergistic actions of growth factors during preimplantation development in the previous sections. It is also possible that the result of combinations of factors may involve a process of interference whereby exposure of embryonic cells to one growth factor may compromise its ability to bind and respond to another.(ABSTRACT TRUNCATED AT 400 WORDS)
It is concluded that in the birds which have been studied there is a well-defined, regular cycle of the seminiferous epithelium, and that spermatogenesis involves synchronization of the activities of germ cells within and between successive generations to produce cellular associations of the seminiferous epithelium which are essentially similar to those described in mammals. However, the area of a cellular association is smaller in birds than in most (and probably all) mammals so that numerous cellular associations are present in a cross-section of a seminiferous tubule. As in primates, in which a cellular association also covers a small area of seminiferous tubule, the wave of spermatogenesis in the Japanese quail follows a spiral path along and around a seminiferous tubule with consecutive stages of the cycle always occurring as adjacent stages along the tubule. The literature indicates that there are fewer mitotic divisions during spermatogonial proliferation in birds than has been reported for mammals and it is suggested that this difference explains the difference between birds and mammals in the area occupied by a cellular association. Work on the Japanese quail indicates that stem cell renewal and spermatogonial proliferation is simpler in the quail than has been described in some mammals. In the quail, both processes occur in the same compartment of the seminiferous epithelium and are synchronized with subsequent phases of spermatogenesis, and there does not seem to be a reserve pool of non-proliferating stem spermatogonia in the quail as has been reported for some mammals. Findings to date also indicate that spermatogenesis in birds is four times faster and produces four times the number of spermatozoa/g testis than in mammals, and that this difference is associated with a faster transit and poorer survival of spermatozoa in the male extragonadal ducts of birds than mammals. These differences between birds and mammals are interpreted as a response to selection pressure due to competition between males to inseminate partners frequently in order to provide the most viable spermatozoa at the site of fertilization when ova are ready for fertilization. In this respect, it is suggested that sperm production in birds and mammals have progressed along different lines of evolutionary development due to differences in ovulatory pattern and mating system. In particular, the high sperm production of birds is associated with the need to mate a (usually monogamous) partner numerous times a day over a period of days or weeks when a clutch of eggs is laid.(ABSTRACT TRUNCATED AT 400 WORDS)
For 50 years after its discovery in 1926, there was a general lack of interest in relaxin among both reproductive biologists and clinicians. A key reason for this lack of interest was the lack of information concerning relaxin's physiological importance during pregnancy in any species. Research conducted since the early 1980s has established that the hormone relaxin is essential during pregnancy in at least two species--rats and pigs. Two vital roles for relaxin during pregnancy have been identified. Relaxin promotes growth and softening of the uterine cervix and thereby enables rapid and safe delivery in both rats and pigs. Relaxin also promotes growth and development of the mammary apparatus in both species. Interestingly, the major effects of relaxin on mammary growth and development are targeted on the nipple in the rat, whereas they are targeted on the glandular parenchyma in the pig. Relaxin-dependent growth of the nipple in rats is required for normal lactational performance. Although likely, it remains to be established that relaxin's profound effects upon mammary gland development in pigs are required for normal lactational performance. The fact that relaxin has effects upon cervical and mammary gland development during pregnancy in both rats and pigs encourages the view that relaxin may have similar effects during pregnancy in other species. Nevertheless, one must keep in mind that there is great diversity in the physiology of relaxin among species (reviewed by Sherwood 1988). This diversity includes not only relaxin's source, regulation of synthesis and secretion, and secretory profiles during pregnancy, but also its biological effects. It seems essentially certain that relaxin's effects during pregnancy differ among species. For example, transformation of the pubic joint cartilage to a flexible and elastic interpubic ligament occurs during pregnancy in several species, including guinea pigs, mice, and bats. This pelvic adaptation, which is nearly certainly relaxin dependent, does not occur in species such as rats and sheep. It is possible that relaxin may have little or no physiological significance during pregnancy in some species. Although considerable progress has been made toward an understanding of the physiological role(s) of relaxin in pregnant rats and pigs, many fundamental questions remain unanswered.(ABSTRACT TRUNCATED AT 400 WORDS)
Cytokines and other small signalling molecules appear to play important roles in determining the success or failure of early pregnancy. Much more information is needed, particularly with respect to interaction effects of the multiple cytokines present in situ and matrix molecules. Further, this author would like to emphasize the importance of experiments which test in vivo the physiologic relevance of factors detected in samples of reproductive tissues using in vitro methods, existentialism notwithstanding.
Considerable research on immunological control of pregnancy has occurred within the last several decades. It indicates that effective contraceptive and interceptive vaccines against pregnancy are possible. It also allows for further research on basic reproductive processes. Studies of the basic reproductive process have revealed potential target antigens. Immunization against structural antigens associated with the sperm surface, zona pellucida, and cumulus oophorus may be a way to prevent fertilization, thereby circumventing the problems associated with abortifacients. Clinical trials are now testing the active immunization technique against human chorionic gonadotropin. If the application of the new immunogens strengthen the reproducibility of the immune response, the active immunization technique may successfully terminate pregnancy. Even though progesterone antagonists, e.g., RU-486, interrupt pregnancy, safe and effective postcoital and anti-implantation vaccines, which do not cause menstrual irregularities, are still needed. Development of these types of vaccine is not going to result in an acceptable vaccine in the near future. Research of basic reproductive biology should continue, because it may lead to the development of a type of fertility control which is more appealing than the longterm hormonal contraceptives now used.
