哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖,是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示,kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加,而雌激素的这种效应是由kisspeptin神经元传导的。因此,kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化,在非繁殖期对繁殖活动的抑制作用非常明显。此外,甲状腺激素在繁殖期的终止上发挥着至关重要的作用,而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖, 是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示, kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加, 而雌激素的这种效应是由kisspeptin神经元传导的。因此, kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化, 在非繁殖期对繁殖活动的抑制作用非常明显。此外, 甲状腺激素在繁殖期的终止上发挥着至关重要的作用, 而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

Regulation of seasonal reproduction in mollusks

Understanding the physiological basis of environmental regulation of reproduction at the cellular level has been difficult or unfeasible in vertebrate species because of the highly complex and diffuse nature of vertebrate neuroendocrine systems. This is not the case with the simple nervous system of mollusks in which reproductive neuroendocrine cells are often readily identifiable in living tissue. Given that there are mollusks that are seasonal breeders, that the neuroendocrine cells controlling reproduction have been identified in several molluskan species, that these neurons are conducive to cell physiological analysis, and that basic features of cell biology have been highly conserved between mammals and mollusks, it seems that the mollusk would provide an excellent model system to investigate cell-physiological events that mediate effects of environmental signals on reproduction. The purpose of this review is to explore this idea in three species in which the topic of the neural basis of seasonal reproduction has been studied: the giant garden slug Limax maximus, the freshwater pond snail Lymnaea stagnalis, and the marine snail Aplysia californica.     

Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in Japanese quail. The Japanese quail provides an excellent avian model for testing EDCs because this species has well-characterized reproductive endocrine and behavioral responses. Considerable research has been conducted in quail in which the effects of embryonic steroid exposure have been studied relative to reproductive behavior. Moreover, developmental processes have been studied extensively and include investigations of the reproductive axis, thyroid system, and stress and immune responses. We have conducted a number of studies, which have considered long-term neuroendocrine consequences as well as behavioral responses to steroids. Some of these studies have specifically tested the effects of embryonic steroid exposure on later reproductive function in a multigenerational context. A multigenerational exposure provides a basis for understanding potential exposure scenarios in the field. In addition, potential routes of exposure to EDCs for avian species are being considered, as well as differential effects due to stage of the life cycle at exposure to an EDC. The studies in our laboratory have used both diet and egg injection as modes of exposure for Japanese quail. In this way, birds were exposed to a specific dose of an EDC at a selected stage in development by injection. Alternatively, dietary exposure appears to be a primary route of exposure; therefore experimental exposure through the diet mimics potential field situations. Thus, experiments should consider a number of aspects of exposure when attempting to replicate field exposures to EDCs.     

Altered reproductive success in rat pairs after environmental-like exposure to xenoestrogen

Endocrine-disrupting compounds (EDCs) have the capacity of altering the normal function of the endocrine system. EDCs have shown dramatic effects on the reproductive biology of aquatic wildlife and may affect human reproduction as well. Studies on EDCs in mammalian species have often investigated the effects of short-term, high doses on male and female reproductive physiology. However, it is difficult to predict from such studies the effects of EDC on populations that are exposed to very low doses throughout their life via contaminated food and water. We studied the effects of EDC on mammalian reproduction with an environmental-like protocol where the endpoint is the reproductive success of exposed pairs. We focused on a subclass of EDC, the xenoestrogens, which mimic the action of natural oestrogen hormones. Male and female rats were exposed to low doses of the pure oestrogen, ethynyloestradiol, during development, by oral administration to their mothers during pregnancy and lactation, and to them until puberty. We evaluated the effects of the exposure on development and reproductive physiology of individuals, and on fertility and fecundity of pairs in which both members had been exposed to the same treatment. We found that low doses caused major reproductive deficits in the experimental animals. Very low, environmentally relevant doses did not have evident effects on exposed animals; however, the fecundity of exposed pairs was substantially altered. Environmentally relevant doses of xenoestrogens which have no evident physiological effects can alter the reproductive success of exposed pairs in natural populations.     

Thyroid hormones in small ruminants: effects of endogenous, environmental and nutritional factors

Appropriate thyroid gland function and thyroid hormone activity are considered crucial to sustain the productive performance in domestic animals (growth, milk or hair fibre production). Changes of blood thyroid hormone concentrations are an indirect measure of the changes in thyroid gland activity and circulating thyroid hormones can be considered as indicators of the metabolic and nutritional status of the animals. Thyroid hormones play a pivotal role in the mechanisms permitting the animals to live and breed in the surrounding environment. Variations in hormone bioactivity allow the animals to adapt their metabolic balance to different environmental conditions, changes in nutrient requirements and availability, and to homeorhetic changes during different physiological stages. This is particularly important in the free-ranging and grazing animals, such as traditionally reared small ruminants, whose main physiological functions (feed intake, reproduction, hair growth) are markedly seasonal. Many investigations dealt with the involvement of thyroid hormones in the expression of endogenous seasonal rhythms, such as reproduction and hair growth cycles in fibre-producing (wool, mohair, cashmere) sheep and goats. Important knowledge about the pattern of thyroid hormone metabolism and their role in ontogenetic development has been obtained from studies in the ovine foetus and in the newborn. Many endogenous (breed, age, gender, physiological state) and environmental factors (climate, season, with a primary role of nutrition) are able to affect thyroid activity and hormone concentrations in blood, acting at the level of hypothalamus, pituitary and/or thyroid gland, as well as on peripheral monodeiodination. Knowledge on such topics mirror physiological changes and possibly allows the monitoring and manipulation of thyroid physiology, in order to improve animal health, welfare and production.     

A review of chemically-induced alterations in thyroid and vitamin A status from field studies of wildlife and fish

This paper reviews 22 published field studies that have found an association between exposure to environmental contaminants and alterations in thyroid gland structure, circulating thyroid hormones and vitamin A (retinoid) status in free-ranging populations of wildlife and fish. Vitamin A and thyroid hormones play critical roles during development, growth and function 'throughout life. Studies of captive wildlife and laboratory studies support a relationship between alterations in thyroid hormones and vitamin A status and exposure to dioxins, furans, and planar polychlorinated biphenyls, which bind to the aryl hydrocarbon receptor. Some studies have found adverse health effects in wildlife associated with exposure to polyhalogenated aromatic hydrocarbons and altered thyroid and retinoid status including: decreased reproductive success, immune system changes, dermatologic abnormalities and developmental deformities. A direct causal relationship between these effects and thyroid and retinoid changes has not been demonstrated. Field researchers studying the responses to these synthetic chemicals in wildlife and fish should include measurement of thyroid hormones and retinoids and histological examination of the thyroid gland in their study design as biomarkers of exposure to these chemicals in the environment.     

Kisspeptin在女性生殖内分泌和辅助生殖技术中的研究进展

近年来研究显示,kisspeptin在大脑的性别分化、性激素正负反馈调节、青春期始动以及机体能量信号转导等生理过程中起到重要作用,表明kisspeptin可能是女性生殖功能成熟及调控的一个关键性信号因子。除下丘脑分泌的kisspeptin之外,生殖器官局部表达的kisspeptin在机体正常生殖过程中的作用也不断得到证实。研究表明,很多生殖内分泌疾病,如单纯性促性腺激素分泌不足的性腺机能减退症(isolated hypogonadotropic hypogonadism, IHH)、多囊卵巢综合征(polycystic ovary syndrome, PCOS)、卵巢早衰(premature ovarian failure, POF)、病理性高泌乳素血症等,都与kisspeptin的异常表达有关。通过给予外源性kisspeptin可解决辅助生殖技术应用中的一些问题。本文主要就kisspeptin在女性生殖内分泌尤其是在辅助生殖领域研究中所取得的进展进行论述。     

At the crossroads of physiology and ecology: Food supply and the timing of avian reproduction

The decision of when to breed is crucial to the reproductive success and fitness of seasonally breeding birds. The availability of food for adults prior to breeding has long been thought to play a critical role in timing the initiation of seasonal reproductive events, in particular laying. However, unequivocal evidence for such a role remains limited and the physiological mechanisms by which an increase in food availability results in seasonal activation of the reproductive system are largely speculative. This lack of mechanistic information partly reflects a lack of integration of ecological and physiological approaches to study seasonal reproduction. Indeed, most work pertaining to the role of food availability for adults on the timing of avian reproduction has been ecological and has focused almost exclusively on female traits associated with reproductive timing (e.g., lay date and clutch size). By contrast, most work on the physiological bases of the relationship between food availability and the timing of reproduction has investigated male traits associated with reproductive development (e.g., reproductive hormones and gonadal development). To advance our understanding of these topics, we review the role of proximate factors including food availability, social factors, and ambient temperature in the control of breeding decisions, and discuss the role of three potential candidates (leptin, glucocorticoids, and GnIH–neuropeptide Y) that may mediate the effects of food availability on these decisions. We emphasize that future progress in this area is heavily contingent upon the use of physiology-based approaches and their integration into current ecological frameworks.     

Angiotensin-converting enzyme as a target for the development of novel insect growth regulators

Insect angiotensin converting enzyme (ACE) is a zinc metallopeptidase capable of inactivating a variety of small to medium size peptide hormones by cleavage of C-terminal dipeptides and dipeptideamides. High levels of ACE activity are found in the hemolymph and in reproductive tissues of insects, where the enzyme is considered to have an important role in the metabolism of bioactive peptides. Therefore, inhibiting ACE activity is expected to interfere with the peptidergic endocrine system and to have detrimental effects on growth, development and reproduction. We will review the studies showing that ACE inhibitors do indeed disrupt growth and reproduction in various insect species. We will also present some new genetic and pharmacological data that strengthens our conclusion that ACE should be considered as a potential target for the development of new insect growth regulators.     

Amphibian metamorphosis as a model for studying the developmental actions of thyroid hormone

The thyroid hormones L-thyroxine and triiodo-Lthyronine have profound effects on postenbryonic development of most vertebrates.Analysis of their action in mammals is vitiated by the exposure of the developing foetus to a number of maternal factors which do not allow one to specifically define the role of thyroid hormone (TH) or that of other hormones and factors that modulate its action.Amphibian metamorphosis is obligatorily dependent on TH which can initiate all the diverse physiological manifestations of this postembryonic developmental process(morphogenesis,cell death,re-structuring,etc.) in free-living embryos and larvas of most anurans.This article will first describe the salient features of metamorphosis and its control by TH and other hormones.Emphasis will be laid on the key role played by TH receptor (TR),in particular the phenomenon of TR gene autoinduction,in initiating the developmental action of TH.Finally,it will be argued that the findings on the control of amphibian metamorphosis enhance our understanding of the regulation of postembryonic development by TH in other vertebrate species.     

Reproductive tolerance in male primates: Old paradigms and new evidence

Within social groups of primates, males commonly compete over reproduction, but they may also rely on cooperation with other males. Theory suggests that it may be adaptive for male primates to tolerate some reproduction by other males if reproductive tolerance fosters cooperation, particularly that dominant males yield so‐called reproductive concessions to subordinates to entice their cooperation. We review four recent studies that claimed to have found evidence for reproductive concessions or similar forms of reproductive tolerance. However, upon critical reevaluation of their results, no study provides conclusive support for reproductive concessions as predicted by theoretical models. Yet two studies demonstrated a form of reproductive tolerance that cannot be explained by any of the existing models, and that seems to have evolved only in multi‐male, multi‐female societies with diverse strategic options for males. Our article provides guidance how to study this form of reproductive tolerance in the absence of a unifying model.     

Cancer susceptibility and reproductive trade-offs: a model of the evolution of cancer defences

The factors influencing cancer susceptibility and why it varies across species are major open questions in the field of cancer biology. One underexplored source of variation in cancer susceptibility may arise from trade-offs between reproductive competitiveness (e.g. sexually selected traits, earlier reproduction and higher fertility) and cancer defence. We build a model that contrasts the probabilistic onset of cancer with other, extrinsic causes of mortality and use it to predict that intense reproductive competition will lower cancer defences and increase cancer incidence. We explore the trade-off between cancer defences and intraspecific competition across different extrinsic mortality conditions and different levels of trade-off intensity, and find the largest effect of competition on cancer in species where low extrinsic mortality combines with strong trade-offs. In such species, selection to delay cancer and selection to outcompete conspecifics are both strong, and the latter conflicts with the former. We discuss evidence for the assumed trade-off between reproductive competitiveness and cancer susceptibility. Sexually selected traits such as ornaments or large body size require high levels of cell proliferation and appear to be associated with greater cancer susceptibility. Similar associations exist for female traits such as continuous egg-laying in domestic hens and earlier reproductive maturity. Trade-offs between reproduction and cancer defences may be instantiated by a variety of mechanisms, including higher levels of growth factors and hormones, less efficient cell-cycle control and less DNA repair, or simply a larger number of cell divisions (relevant when reproductive success requires large body size or rapid reproductive cycles). These mechanisms can affect intra- and interspecific variation in cancer susceptibility arising from rapid cell proliferation during reproductive maturation, intrasexual competition and reproduction.     

Theory on the evolutionary history of lamprey metamorphosis: role of reproductive and thyroid axes

Metamorphosis is a developmental strategy used by only a small number of extant fishes and little is known about its phylogenetic development during the evolution history of this large group of vertebrates. The present report provides a putative evolutionary history of metamorphosis in the lamprey, an extant agnathan with direct descendancy from some of the oldest known vertebrates. The study reviews recent data on the role of the thyroid gland and its hormones in metamorphosis, summarizes some recent views on the evolution of the endostyle/follicular thyroid in lampreys, and provides new data on the content of two gonadotropin-releasing hormones (GnRH-I and -III) in brain during goitrogen-stimulated, precocious metamorphosis. These new data support an earlier viewpoint of a relationship between thyroid and reproductive axes during metamorphosis. It is proposed that the earliest lampreys were paedomorphic larvae and they lived in a marine environment; as such, they resembled in many ways the larvae from which the ancient protochordates, Larvacea, are derived. The iodide-concentrating efficiency of the endostyle was a critical factor in the evolution of metamorphosis and this gland was replaced by a follicular thyroid, for postmetamorphic animals needed to store iodine following their invasion of freshwater. Larval growth and postmetamorphic reproduction in freshwater became fixtures in the lamprey life cycle; a non-parasitic adult life-history type appeared later. The presence among extant lampreys of two different adult life-history types, and examples of the lability of the timing of sexual maturation in some species, imply that there has been a complex interplay between the thyroid and reproductive axes during the evolution of metamorphosis in lampreys. This proposal is consistent with what we know of interplay of these axes in extant adult lampreys and with the long-held viewpoint that thyroid function and sexual maturation are an association with an ancient history.     

Hormonal control of reproduction and reproductive behavior in crickets

In Orthoptera, the endocrine control of reproduction has been investigated mainly in Acrididae. Gryllidae are also good models for the study of hormonal control of reproduction and reproductive behavior. In this review, special attention will be focused on the house cricket, Acheta domesticus. In the house cricket, vitellogenesis is controlled according to the classical model described for most insect orders. However, whereas allatectomy completely abolished oocyte growth in A. domesticus, it did not totally suppress ovarian development and egg-laying in Teleogryllus commodus, Gryllus bimaculatus, and G. campestris. In the Gryllidae studied thus far, juvenile hormone (JH) is not needed for mating behavior. In adult A. domesticus, the expression of oviposition movement, although independent of the presence of the ovaries, is strictly controlled by JH III. Recent findings suggest hormonal actions on the central nervous system of the house cricket, and provide a stimulating basis for further research on the respective involvement of hormones and nervous system in the control of reproductive behavior in adult crickets. Arch. Insect Biochem. Physiol. 35:393–404, 1997. © 1997 Wiley-Liss, Inc.     

The song of the old mother: Reproductive senescence in female drosophila

Among animals with multiple reproductive episodes, changes in adult condition over time can have profound effects on lifetime reproductive fitness and offspring performance. The changes in condition associated with senescence can be particularly acute for females who support reproductive processes from oogenesis through fertilization. The pomace fly Drosophila melanogaster is a well-established model system for exploring the physiology of reproduction and senescence. In this review, we describe how increasing maternal age in Drosophila affects reproductive fitness and offspring performance as well as the genetic foundation of these effects. Describing the processes underlying female reproductive senescence helps us understand diverse phenomena including population demographics, condition-dependent selection, sexual conflict, and transgenerational effects of maternal condition on offspring fitness. Understanding the genetic basis of reproductive senescence clarifies the nature of life-history trade-offs as well as potential ways to augment and/or limit female fertility in a variety of organisms.     

The song of the old mother: Reproductive senescence in female drosophila

Among animals with multiple reproductive episodes, changes in adult condition over time can have profound effects on lifetime reproductive fitness and offspring performance. The changes in condition associated with senescence can be particularly acute for females who support reproductive processes from oogenesis through fertilization. The pomace fly Drosophila melanogaster is a well-established model system for exploring the physiology of reproduction and senescence. In this review, we describe how increasing maternal age in Drosophila affects reproductive fitness and offspring performance as well as the genetic foundation of these effects. Describing the processes underlying female reproductive senescence helps us understand diverse phenomena including population demographics, condition-dependent selection, sexual conflict, and transgenerational effects of maternal condition on offspring fitness. Understanding the genetic basis of reproductive senescence clarifies the nature of life-history trade-offs as well as potential ways to augment and/or limit female fertility in a variety of organisms.     

The role of extrinsic and intrinsic factors in the evolution of the control of pulmonary surfactant maturation during development in the amniotes

Pulmonary surfactant is a mixture of lipids and proteins that is secreted by alveolar Type II cells. It reduces alveolar surface tension and hence the work of breathing. Despite the tremendous diversity of lung structures amongst the vertebrates, the composition of surfactant is highly conserved. Conserved elements of the surfactant system amongst distantly related species are likely to be crucial factors for successful lung development. Understanding the mechanisms by which the surfactant system becomes operational in animals with dramatically different birthing strategies and in distantly related species will provide important information about the role of the surfactant system in the commencement of air breathing and the processes regulating surfactant maturation and secretion. In mammals, the embryonic maturation of the surfactant system is controlled by a host of factors, including glucocorticoids, thyroid hormones, and autonomic neurotransmitters. Here we review the mechanisms controlling the maturation of surfactant production, including birthing strategy, phylogeny, lung structure, and posthatching environment. Using four species of egg-laying amniote (chicken, dragon lizard, sea turtle, and crocodile) previously described in detail and the large amount of information available for mammals, we examine the hypothesis that the control of surfactant production is dependent on glucocorticoids (dexamethasone [Dex]), thyroid hormones (T3), and autonomic neurotransmitters (epinephrine and carbachol). We also examine whether the overall intrinsic pattern of the control of surfactant maturation is conserved throughout the vertebrate radiation and then how the environment (extrinsic factors) may account for the observed differences in the patterns of development. We also discuss the utility of a coculture system of embryonic Type II cells and fibroblasts to determine the evolutionary pattern behind the control of surfactant and to demonstrate that the surfactant system matures under multihormonal control. We demonstrate that Dex and T3 are stimulators of surfactant production during embryonic development, but they lose their efficacy closer to hatching or birth. Epinephrine stimulates surfactant secretion beyond 75% of development and also after hatching or birth. Carbachol stimulates surfactant secretion in the bearded dragon and saltwater crocodile but not in the sea turtle, chicken, or mammals. It is likely that the differences in control of surfactant development are likely to be primarily related to metabolic activity and the duration of incubation (i.e., the "speed" of development). Moreover, the hormones examined appear important in promoting development and therefore appear conserved within the amniotes. However, the autonomic neurotransmitters induced different responses in different species. Hence, some factors are crucial for the proper maturation of the surfactant system, whereas others vary throughout evolution without being detrimental to the overall function of the system.