How behavioral stress disrupts the endocrine control of reproduction in domestic animals

Behavioral stress can prevent animals from achieving normal reproductive success. Stressors associated with intensive livestock management may be responsible for reduced reproductive efficiency. However, before appropriate management decisions can be made to alleviate the effects of behavioral stress on reproduction, it is necessary to identify the mechanisms by which stress disrupts normal reproduction. The neuroendocrine regulation of follicular development and ovulation requires a complex and delicate interplay between the pituitary gonadotropins and the feedback actions of the major follicular steroid, estradiol. Because of this complexity, the regulation of the follicular stage of the estrous cycle and ovulation is especially vulnerable to the effects of stress. Although the pathophysiological mechanisms by which stress disrupts reproduction are not fully understood, the stress-induced secretion of adrenal glucocorticoids seems to be of special significance because these steroids can effect both the synthesis and secretion of gonadotropins. Of additional importance may be the role of corticotropin-releasing hormone and adrenocorticotropin on the regulation of the hypothalamic-pituitary-gonadal axis.     

Zinc, exercise, and thyroid hormone function.

During the last 3 decades, remarkable advances have taken place in the field of zinc metabolism. Thirty years ago, only three enzymes that required zinc for their activities were identified; today more than 200 such enzymes have been classified. Zinc plays a vital role in human nutrition and biochemical function. Prior to 1963, zinc deficiency in humans was unknown. Today, it is recognized that a nutritional deficiency of zinc is common throughout the world, including the U.S.A marginal deficiency of zinc appears to be prevalent in many segments of populations in developed countries, and more severe deficiencies are widespread in many parts of the world. Therefore, it is important that proper steps to correct zinc deficiency are taken. However, the assessment of zinc nutriture has always proven to be a difficult problem because no reliable measure of zinc status currently exists. More recently, it has been recognized that zinc may play an important role in thyroid hormone metabolism, although the exact mechanism by which zinc affects thyroid hormone function is far from clear. In addition, exercise has been shown to alter zinc status. This review will focus on the relationship among zinc status, exercise, and thyroid hormone function.     

Reproductive role of prolactin

The biological actions of prolactin (PRL), a polypeptide hormone, are mostly related to lactation and reproduction. These actions have been clarified by studies of PRL and PRL-deficient receptor mice, which have a clear phenotype of reproductive failure at multiple sites. This review aims to summarize current knowledge about PRL and its receptor, role in reproductive axis and presents information of hyperprolactinemia in reproductive medicine. Our understanding of the physiology and transduction pathway of PRL has largely increased in the past 20 years with the cloning of PRL and its receptor gene.     

Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase in circulating testosterone. The activation of pituitary cells by Kp was inhibited by preadministration of the GNRH receptor antagonist acyline. Altogether, our results demonstrate that peripheral Kp54 activates the gonadotropic axis by stimulating GNRH release and indicate that an appropriate protocol of long-term systemic Kp administration can recrudesce a photo-inhibited reproductive axis.     

The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output

Neuron-to-glia, glia-to-neuron, and glia-to-glia communication are implicated in the modulation of neuronal activity and synaptic transmission relevant to reproduction. Glial cells play an important role in neuroendocrine regulation and participate in the sexual differentiation of neuronal connectivity of brain regions involved in the control of reproductive neuroendocrine output. During puberty, modifications in the morphology and chemistry of astrocytes and tanycytes in the hypothalamus and median eminence influence the maturation of the neuronal circuits controlling the secretion of GnRH. During adult reproductive life, the glial cells participate in the transient remodeling of neuronal connectivity in the preoptic area, the arcuate nucleus, the median eminence, and other brain regions involved in the control of reproduction. Gonadal hormones regulate glial plasticity by direct and indirect effects and regulate various other endocrine signals, local soluble factors and adhesion molecules that also affect glial function and glia-to-neuron communication. The glial cells, therefore, are central to the coordination of endocrine and local inputs that bring about neural plasticity and adapt reproductive capacity to homeostatic signals.     

Prenatal programming of the female reproductive neuroendocrine system by androgens

It has been clear for several decades that the areas of the brain that control reproductive function are sexually dimorphic and that the 'programming actions' of the male gonadal steroids are responsible for sex-specific release of the gonadotrophins from the pituitary gland. The administration of exogenous steroids to fetal/neonatal animals has pinpointed windows of time in an animals' development when the reproductive neuroendocrine axis is responsive to the organisational influences of androgens. These 'critical' periods for sexual differentiation of the brain are trait- and species-specific. The neural network regulating the activity of the gonadotrophin releasing hormone (GnRH) neurones is vital to the control of reproductive function. It appears that early exposure to androgens does not influence the migratory pathway of the GnRH neurone from the olfactory placode or the size of the population of neurones that colonise the postnatal hypothalamus. However, androgens do influence the number and the nature of connections that these neurones make with other neural phenotypes. Gonadal steroid hormones play key roles in the regulation of GnRH release acting largely via steroid-sensitive intermediary neurones that impinge on the GnRH cells. Certain populations of hormonally responsive neurones have been identified that are sexually dimorphic and project from hypothalamic areas known to be involved in the regulation of GnRH release. These neurones are excellent candidates for the programming actions of male hormones in the reproductive neuroendocrine axis of the developing female.     

Trace element deficiencies and fertility in ruminants: a review.

Various minerals (copper, cobalt, selenium, manganese, iodine, zinc, and iron) can influence reproductive performance of ruminants. Reproductive failure may be induced by deficiencies of single or combined trace elements and by imbalances. This review is focused on maladjustments of trace elements leading to impaired breeding performance. Opinion is diverse as to the existence of various reproductive disturbances from either a severe copper depletion or a marginal dietary copper deficiency. Field experience suggests that administration of cobalt to ruminants on cobalt-deficient diets improves their impaired breeding performance. Selenium infertility in ewes is more prevalent in some areas and in some seasons, but the actual cause of this malady and the continuing role of additional factors are unknown. Manganese is necessary for normal fertility in ruminants, and feeding low-manganese rations depresses conception rates. Lack of iodine impairs thyroid activity and also ovarian function. Reproductive failure in the female and in spermatogenesis are manifestations of zinc deficiency. Despite forages rich in iron, low availability in certain instances could affect adversely ruminant reproduction. Knowledge of biochemical dysfunctions from trace element deficiencies is essential to determine the role which trace elements play in fertility of ruminant animals.     

Effects of the antithyroid agent propylthiouracil in a partial life cycle assay with zebrafish

Some ubiquitous pollutants of the aquatic environment, such as PCBs or other polyhalogenated aromatic hydrocarbons, may disrupt the thyroid hormone system. In a partial life cycle assay with zebrafish (Danio rerio), we studied the effects of the reference compound propylthiouracil (PTU) on reproduction, growth and development, histopathology of some target tissues, and plasma thyroid hormone levels. PTU induced a concentration-dependent increase of egg production with a concomitant decrease of mature oocyte size but had no effect on fertilization rate or hatching. In F1, serious dysmorphogenesis was found in 4 dph larvae at the highest PTU level tested (100 mg/L), and there was a dose-dependent decrease in body length and weight at 42 dph (significant at 100 mg/L PTU). At this time, there was also a decreased scale thickness, suggesting inhibited metamorphosis, detectable at 1 mg/L PTU and higher. PTU also induced activation of the thyroid follicles in a concentration-dependent way, in juveniles associated with hyperemia in the thyroid area, and depletion of liver glycogen. Effects in adults were associated with decreased circulating levels of the thyroid hormones T3 and T4. These observations indicate that disruption of the thyroid hormone system may affect the fitness of these aquatic organisms. The zebrafish model may contribute to the identification of thyroid hormone disrupting activity in water samples and also in the interpretation of histological observations in free-ranging fish species.     

Insulin-like growth factors-I and -II and insulin-like growth factor-binding protein-2 in dominant equine follicles during spring transition and the ovulatory season

The period between seasonal anoestrus and cyclicity is characterized in many mares by cyclical growth and regression of large dominant follicles. The insulin-like growth factor (IGF) system plays a key role in follicular growth and regression; therefore, we hypothesized that changes in the IGF system and its binding proteins would modulate onset of cyclicity in mares. Ovaries were obtained from pony mares on the day after detection of an actively growing 30 mm transitional anovulatory follicle, and also at the second or third oestrus of the breeding season on the day after the preovulatory follicle reached 30 mm in diameter. Size of dominant follicles at the time of removal was similar in transition (32 +/- 0.8 mm) and at oestrus (34 +/- 0.6 mm). IGF-I mRNA was present in granulosa cells, with low thecal expression, whereas IGF-II mRNA was confined to the theca layer. Expression of IGF-I and -II mRNAs, and intrafollicular concentrations of oestradiol, were lower (P < 0.01; paired t test) in transitional anovulatory follicles than in preovulatory follicles. Messenger RNA encoding IGFBP-2 was present in both theca and granulosa layers. Steady-state concentrations of mRNA encoding IGFBP-2 mRNA increased (P < 0.001) in theca in preovulatory follicles. Intrafollicular concentrations of IGFBP-2 were higher (P < 0.001) in transitional than in preovulatory follicles. The similarity in circulating concentrations of IGF-I in transitional and cyclic mares, suggested that the somatotrophic axis is not involved in transition from anovulatory to ovulatory cycles. The results suggest that the increased expression of IGF-I and -II mRNAs in preovulatory follicles, along with the decrease in IGFBP-2 concentrations, could increase the bioavailability of intrafollicular IGF in large follicles during the breeding season, and support our hypothesis that intrafollicular IGF bioavailability must exceed a threshold level before ovulation can occur.     

Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity

A series of epidemiological, clinical and experimental studies have shown that there are associations between the fetal and neonatal nutritional environment and the amount and distribution of adipose tissue in adult life. This review considers the evidence for these relationships and discusses the potential impact of the prenatal nutritional experience on the development of the endocrine and neuroendocrine systems that regulate energy balance, with a particular emphasis on the role of the adipocyte-derived hormone, leptin. In the rodent, leptin derived from the mother may exert an important influence on the development of the appetite regulatory neural network and on the subsequent regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, there is also recent evidence that the synthesis and secretion of adipocyte-derived hormones, such as leptin, are regulated in fetal life. Furthermore, the hypothalamic neuropeptides that regulate energy intake and expenditure in adult life are also present within the fetal brain and may be regulated by the prevailing level of maternal and hence fetal nutrient and hormonal signals, including leptin. This work is important in determining those initiating mechanisms within the 'fat-brain' axis in early life that precede the development of adult obesity.     

Anti-Mullerian hormone as a predictive endocrine marker for embryo production in the goat

Recently, we demonstrated the relationship between anti-Müllerian hormone (AMH) circulating concentrations, ovarian follicles, and embryo production in cattle. However, they have not yet been established in a species with a seasonal breeding activity. Thus, goats were subjected to repeated in vivo embryo production during the breeding season, at the end of the breeding season, and at the end of the anestrus season. Embryo production after FSH treatment was highly repeatable for each goat. Plasma AMH concentrations, measured before the first FSH treatment, were highly correlated with the number of collected, transferable, and freezable embryos, resulting from the three sessions of embryo production. Plasma AMH concentrations transiently decreased after each exogenous FSH treatment, but they showed little change with season, and no relationship was observed between AMH and endogenous FSH concentrations during seasonal transitions. Follicles of 1-5 mm in diameter were the main target of the FSH treatment and were major contributors to circulating AMH concentrations. Granulosa cell AMH expression decreased as the follicle approached terminal development, while the expression of maturation markers (CYP19A1 and FSHR) increased. In conclusion, circulating AMH concentrations can be predictive of the capacity of a donor goat to produce high or low numbers of high-quality embryos. This prediction could be accurately made from a single blood measurement of AMH during either breeding or anestrus seasons. Variability in the number of gonadotropin-responsive follicles of 1-5 mm in diameter between individuals resulted in the differences in circulating AMH concentrations measured between individuals.     

Parental transfer of polybrominated diphenyl ethers (PBDEs) and thyroid endocrine disruption in zebrafish

Polybrominated diphenyl ethers (PBDEs) have the potential to disrupt the thyroid endocrine system. The objective of the present study was to characterize the disrupting effects of long-term exposure on the thyroid endocrine system in adult fish and their progeny following parental exposure to PBDEs. Zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations (1, 3, and 10 μg/L) of the PBDE mixture DE-71 for 5 months until sexual maturation. In the F0 generation, exposure to DE-71 significantly increased plasma thyroxine (T4) but not 3,5,3'-triiodothyronine (T3) in females. This increased T4 was accompanied by decreased mRNA levels of corticotropin-releasing hormone (CRH) and thyrotropin β-subunit (TSHβ) in the brain. The F1 generation was further examined with or without continued DE-71 treatment conditions. Exposure to DE-71 in the F0 fish caused significant increases in T4 and T3 levels in the F1 larvae and modified gene expressions in the hypothalamic-pituitary-thyroid axis (HPT axis) under both conditions. Decreased hatching and inhibition of growth in the F1 offspring were observed in the condition without DE-71 treatment. Continued DE-71 treatment in the F1 embryos/larvae resulted in further decreased hatching, and increased malformation rates compared with those without DE-71 exposure. Analysis of F1 eggs indicated that parental exposure to DE-71 could result in a transfer of PBDEs and thyroid hormones (THs) to their offspring. For the first time, we demonstrated that parental exposure to low concentrations of PBDEs could affect THs in the offspring and the transgenerational PBDE-induced toxicity in subsequent nonexposed generations.     

Physiology of the somatotropic axis with particular reference to the ruminant

The physiology of growth hormone and the insulin-like growth factors are reviewed with particular reference to the dairy industry. Growth hormone secretion in the ruminant is pulsatile in nature and nutritional factors have a major impact on its secretion. Isolation of growth hormone-releasing factor has allowed further progress in understanding the mechanisms underlying growth hormone release. The receptors appear to be under active endocrine and metabolic control, and nutritional influences on the somatotropic axis are in large part mediated through changes in somatotropic receptors. The mode of action of growth hormone to induce acute metabolic affects and lipolysis remains to be resolved, but there is increasing evidence that its anabolic actions are mediated by the insulin-like growth factors. Recent studies of measurement of insulin-like growth factor-1 and -2 in the ruminant and the role of growth hormone, nutrition, insulin, and sex steroids in their regulation are reviewed. The relative role of the two factors and the multiple forms of their receptors remain to be resolved. It is well-documented that growth hormone is galactopoietic. The evidence that this effect is largely due to enhanced nutrient supply to the mammary gland is not convincing. Effects of growth hormone are indirect and may be mediated by the insulin-like growth factors. The potential is considerable for manipulating the growth hormone insulin-like growth factor axis to enhance lactation.     

Biotransformation enzymes and thyroid axis disruption in juvenile rainbow trout (Oncorhynchus mykiss) exposed to hexabromocyclododecane diastereoisomers

Juvenile rainbow trout (Oncorhynchus mykiss) were fed either a reference diet or one of three diets enriched with alpha, beta, or gamma diastereoisomers of hexabromocyclododecane (HBCD, C12H18Br6) for 56 days. This exposure period was followed by 112 days during which all fish were fed the reference diet. Potential effects of HBCD on phase I and II biotransformation enzyme activities and thyroid axis disruption were examined. Disruption of the thyroid axis was most evident in the gamma-HBCD exposed group, as indicated by lower circular FT4 and higher FT3 as well as an increase in thyroid epithelial cell height. However, fish fed the alpha-HBCD enriched diet also exhibited altered glucuronyltransferase activity and thyroid epithelial cell heights and the beta-HBCD group had altered FT4 and FT3 and glucuronyltransferase activity. T4ORD activity was not affected after 14 days, but was significantly lower among all HBCD exposed fish compared to the reference fish after 56 days. Results from these experiments indicate that all isomers have the potential to disrupt thyroid homeostasis.     

牡蛎肽对肾阳虚大鼠下丘脑-垂体-甲状腺轴调节作用的研究

目的:研究牡蛎肽对肾阳虚大鼠下丘脑-垂体-甲状腺轴的调节作用。方法:采用肌肉注射氢化可的松建立肾阳虚大鼠模型,连续灌胃35 d,观察不同剂量牡蛎肽(300、150和75 mg/kg)对模型大鼠的影响,测定血清游离三碘甲状腺原氨酸(T3)、血清游离四碘甲状腺原氨酸(T4)、血清促甲状腺素(TSH)、下丘脑促甲状腺素释放激素(TRH)mRNA表达及甲状腺病理变化。结果:与正常组相比,肾阳虚模型组大鼠的T3、T4、TRH mRNA水平明显极显著降低(p<0.01),TSH水平极显著升高(p<0.01)。肾阳虚模型组动物还表现出甲状腺数量减少、滤泡不清晰及炎性细胞浸润等病理变化。与模型组相比,牡蛎肽组(300和150 mg/kg)动物各激素水平有显著性变化(p<0.05)并趋于正常水平。300 mg/kg剂量牡蛎肽还可明显改善模型动物甲状腺病理变化。结论:牡蛎肽可改善肾阳虚模型大鼠血清激素水平及下丘脑TRH mRNA表达,调节肾阳虚模型大鼠下丘脑-垂体-甲状腺轴。     

微生物-肠-脑轴对肥胖调控的研究进展

肥胖已经成为一种全球性的流行病,严重威害人们的健康和生命,预防和治疗肥胖是世界各国面临的重大公共卫生挑战。越来越多的研究发现肥胖的发生和发展与肠道菌群有着密切的关系,肠道菌群与肥胖之间的调控机制成为研究的热点。微生物-肠-脑轴是肠道菌群参与的肠道和大脑的双向信息交流系统,是大脑和肠道功能相互整合、相互调节的途径。近年国内外的研究表明,微生物-肠-脑轴在肥胖调控方面具有重要的贡献,很多物质通过该途径发挥降脂减肥功能。本文综述了肥胖的严峻现状、微生物-肠-脑轴的组成以及调控肥胖的机制,以期为治疗肥胖等代谢疾病提供思路,也为一些降脂物质的机理研究提供了方向。     

短链脂肪酸-酰化淀粉对小鼠抑郁样行为的缓解及机制

大量研究证实“微生物-肠-脑轴”在抑郁症的发生发展中发挥重要作用,而肠道微生物产生的短链脂肪酸(short chain fatty acids,SCFAs),更是参与神经调控作用的关键分子。该研究首次采用SCFA-酰化淀粉在大肠定点释放5类短链脂肪酸,探究其对慢性应激诱导的抑郁症状的缓解及机制。以雄性C57BL/6 J小鼠为研究对象,通过为期5周的慢性不可预知温和应激构建抑郁小鼠模型,通过旷场实验、高架十字迷宫实验和强迫游泳实验对小鼠的抑郁样行为进行评价。同时对小鼠应激激素、神经递质水平及相关酶的表达水平进行检测。结果显示,乙酸、异丁酸和丁酸能在不同程度上减轻小鼠抑郁样行为,其可能机制与SCFAs修复下丘脑-垂体-肾上腺轴反馈调节障碍、恢复5-羟色胺的正常代谢相关。该研究为抑郁症的营养干预提供了新的理论依据。     

Relationships between reproduction traits, age and body weight at calving, and days dry in first lactation Ayrshires and Holsteins

Individual cow test day records collected between December 1979 and June 1986 were used to calculate measures of reproductive performance, age and weight at calving, and days dry for 7824 Ayrshire and 79,755 Holstein cows in first lactation. Separate analyses by breed were carried out according to a multiple-trait mixed model. Sixty-two Ayrshire and 369 Holstein sires were treated as random in the analyses. Ayrshires were, on average, older and lighter at calving than Holsteins, but the breeds differed little in reproduction measures and days dry. Heritabilities of fertility traits, days to first breeding, days open, and services per conception were all less than .015 in the multi-trait analyses. With the exception of body weight, heritability estimates for the other traits were less than .05. Phenotypic correlations between traits were almost identical for the two breeds, and genetic correlations tended to be similar. Exceptions involved the trait days to first breeding and services per conception, but heritabilities of these traits were close to zero (p less than .008) in Ayrshires. Fertility traits were positively correlated genetically. Genetic correlations between days open and both age and body weight at calving were small. The genetic correlation between age and weight at calving was -.90 and -.68 in Ayrshires and Holsteins, respectively. Genetic correlations between days dry and all traits except body weight were moderate and positive.