Intracerebroventricular leptin injection affects neuroendocrine reproductive axis in ovariectomized rats

BACKGROUND：Leptin regulates neuroendocrine function of the hypothalamus-pituitary-ovary axis in humans. OBJECTIVE： To verify effects of intracerebroventricular leptin injection on neuroendocrine function of the hypothalamus-pituitary-ovary axis in ovariectomized rats. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Basic Medical Institute, Chengde Medical College between June and October 2007. MATERIALS： Thirty healthy, female, Wistar rats were included in this study. The following compounds were used： leptin; gonadotropin-releasing hormone （GnRH） and luteinizing hormone （LH） enzyme-linked immunosorbent assay kits. METHODS： Rats were randomly divided into 3 groups at 1, 2, and 4 hours after injection. Each group was subdivided into control and experimental groups （n = 5 animals per group and time point）. All rats were subjected to bilateral ovariectomy and, beginning on day 7 after surgery, animals received daily subcutaneous injections of estradiol benzoate （2 μg） for 7 consecutive days. The experimental groups were injected with 5 μL leptin （1 g/L） into the lateral cerebral ventricle, and control groups received an equal volume of physiological saline. MAIN OUTCOME MEASURES： GnRH and LH secretion were examined 1, 2, and 4 hours after injection using GnRH and LH ELISA kits, respectively. RESULTS： In the experimental groups, GnRH secretion significantly increased （P 〈 0.01）, followed by LH secretion （P 〈 0.01）, compared with the control groups. GnRH secretion significantly increased 1 hour after leptin injection （P 〈 0.01）. The LH increase was less pronounced, but still significant （P 〈 0.01）; however, the most prominent LH increase occurred between 1 and 2 hours. Both GnRH and LH secretion reached peak levels at 2 hours after leptin injection. Thereafter, both GnRH and LH secretion decreased, but still maintained very high levels, compared with the control group （P 〈 0.01）. CONCLUSION： Intracerebroventricular leptin injection produced similar effects on GnRH and LH secretion in ovariectomized rats, indicating regulatory effects of leptin on GnRH and LH secretion.

Does alcohol have any effect on male reproductive Function？ A review of literature

Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.

Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring

Objective To evaluate the health effects of parental dietary exposure to GM rice TT52 on the male reproductive system of rat offspring. Methods Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats （15 males/30 females each group） for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents＇ for 70 days. The effects of exposure to TT52 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones （FSH, LH, and testosterone levels）, testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular （HPT） axis. Results No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis. Conclusion The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.

Association of Body Mass Index with Hypothalamus-Pituitary-Ovarian Axis Hormones in Infertile Women in the Niger Delta Region, Nigeria

Background: Infertility is well-known global health problem that has significant impacts on an individual, families and communities. Many modifiable lifestyle risk factors increase the risk of women to several reproductive disorders. Aim: This study established the relationship between obesity and Hypothalamic-Pituitary-Ovarian (HPO) axis hormones in infertile women in the Niger Delta Region, Nigeria. Methodology: Six hundred and twenty-six (626) women aged 18 - 40 years comprising of 513 obese infertile women and 113 non obese women who served as control were recruited for the study. Anthropometric measurements were taken and Body Mass Index was calculated. A non-fasting venous blood sample was collected from the women and analyzed for serum Estrogen, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Progesterone, Inhibin B, and Prolactin using Enzyme linked immunosorbent assay method. Results: In the present study, the Body Mass Index of women with primary (1°) infertility is significantly (p < 0.05) higher than secondary (2°) infertility women. Whereas, women with 2° infertility were older and have a higher height than women with 1° infertility. The result revealed that serum estrogen, luteinizing hormone, follicle stimulating hormone and prolactin levels were significantly (p < 0.05) higher in the obese infertile women, while inhibin B and progesterone levels were significantly (p < 0.05) reduced in the obese infertile women compared to the control subjects. However, women with 1° infertility have a significantly higher LH and FSH levels than the 2° infertility women. Furthermore, the study revealed that hyperestrogenism is the most prevalent gonadal disorder in women with primary infertility and secondary infertility. The BMI of infertile women suffering Hyperestrogenism is significantly higher than any other female gonadal disorder. The result also showed that there is statistically significant positive correlation between BMI and Hypogonadism, Hypogonadotropic and Amenorrhoea in obese infertility women. While, no significant correlation between BMI and Hypergonadism and Hypergonadotropic was observed. Furthermore, there was a positive correlation between BMI and Hypothalamus-Pituitary Ovarian hormones, as BMI showed a positive correlation with LH, FSH, Estrogen, progesterone, and prolactin in women with primary and secondary infertility, while Inhibin B showed a negative correlation with BMI. Conclusion: There is a relationship between BMI and Hypothalamus-Pituitary Ovarian hormones, signifying that obesity could affect female reproduction and directly impact ovarian function. Therefore, body weight maintenance should be considered as a first line of management of Hypothalamus-Pituitary Ovarian hormonal related infertility.

基于“心-肾-冲任-胞宫”生殖轴探析妇科生殖疾病的针灸治疗思路

本文主要阐述基于尤昭玲教授“心-肾-冲任-胞宫”生殖轴理论的“生殖十八针”针灸治疗方案。“生殖十八针”以调节妇科生殖疾病中紊乱的生殖轴为目的,选取生殖轴主要脏腑经络上的穴位为主穴,调节相关脏腑气血的穴位为配穴,通过特定操作手法,调气血,疏经络,治脏腑,从而养精助孕,为妇科生殖疾病的针灸治疗提供思路与参考依据。

基于“肾主生殖”理论探讨中医治疗DOR型不孕症的生物学机制

在中医学“肾主生殖”的理论指导下,中医治疗不孕症多以补肾为主。卵巢储备功能下降(diminished ovarian reserve,DOR)是临床导致不孕症的主要病因,DOR型不孕症的发病率逐年增加且发病年龄呈年轻化趋势。中医补肾法在治疗DOR型不孕症方面具有独特优势,其生物学机制主要是调节下丘脑-垂体-卵巢轴神经内分泌功能、抑制卵巢颗粒细胞异常程序性死亡、调节免疫功能、改善卵巢过度氧化应激状态、改善线粒体功能、调节子宫内膜容受性,从而改善卵巢功能,提高生育能力。对近年来中医补肾法治疗DOR型不孕症的生物学机制进行总结,为临床应用“肾主生殖”理论治疗DOR型不孕症提供新思路。

基于“脑-心-肾-精室”轴辨治男性不育症的优势环节

“脑-心-肾-精室”轴理论是基于《黄帝内经》与现代男性疾病发病特点所提出的辨治理论。该理论体现了中医药治疗男科疾病中“身心同调”“整体与局部同治”的特点,通过脑肾相通、脑心同调、心肾互滋以及发挥精室之用,分别在中医药治疗男性不育症的优势环节(生殖内分泌、精神心理状态、生殖微循环与生精微环境)起指导作用。

基于“脑-心-肾-精室”轴探讨男性生殖衰老病机及辨治思路

“脑-心-肾-精室”轴在男科疾病的发生发展中具有重要作用,其失调是导致男性生殖衰老的核心。脑、心、肾作为生命活动的主体,所主之精血神耗损,可引起精室失用,发为男性生殖衰老,常表现为生精能力下降、性功能减退、雄激素水平下降等男性特有的衰老特征等。在“脑-心-肾-精室”轴理论的指导下,防治男性生殖衰老可通过补肾填精、燮理阴阳,调畅心脑、养心安神,清除瘀阻、通利精室等治法调养精血神以恢复精室功用,从而延缓男性生殖衰老。

Long-term exposure to aryl hydrocarbon receptor agonist neburon induces reproductive toxicity in male zebrafish(Danio rerio)

Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it causes reproductive toxicity is not clear.In the present study,zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon(0.1,1 and 10μg/L)induce reproductive disorder in males.After exposure to neburon for 150 days from embryo to adult,that the average spawning egg number in high concentration group was 106.40,which was significantly lower than 193.00in control group.This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain,such as secretogranin-2a.The proportions of spermatozoa in the medium and high concentration groups were 82.40%and 83.84%,respectively,which were significantly lower than 89.45%in control group.This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells.The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment.Neburon treatment also significantly activated the AhR signaling pathway,causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group.Together,these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.

补肾方药治疗肾虚所致男性生殖功能衰减的药效和机制研究进展

有关高龄育子和少子化的现状表明,男性生殖功能衰减带来不育风险的防治问题日益突出。男性生殖功能衰减与下丘脑-垂体-性腺轴、氧自由基、血睾屏障、生精细胞凋亡等因素有密切关系。中医认为,肾藏精,主生殖,生殖功能衰减与肾之阴阳失衡密切相关,运用补肾法可治疗肾虚导致的生殖功能衰减。补肾类方药通过系统调节下丘脑-垂体-性腺轴的功能,可显著延缓生殖功能的衰退;补肾类方药可清除体内过多的氧自由基,保护细胞免受氧化损伤;补肾类方药可通过维持血睾屏障而改善生精功能,并能调控生精细胞的凋亡。通过补肾改善肾虚所致生殖功能衰减的代表性方剂有五子衍宗丸、肾气丸、右归丸、六味地黄丸、左归丸及龟鹿二仙膏。这些方剂并非只针对单一机制产生效果,而是通过多途径、多环节、多靶点发挥治疗作用,综合调节机体内环境,以达到改善男性生殖功能的目的。中医补肾疗法在男性生殖功能衰减的治疗中发挥着不可替代的作用。深入研究其作用机制,可更好地指导临床实践,为改善男性生殖功能衰减提供理论依据。

基于玄府调控生殖轴理论探讨风药在月经病中的运用

风药具有风之轻扬上升、发散开泄、善行而无处不至的特性,能开通全身上下内外之玄府,是临床最常用的一类开通玄府药物。因此,在月经病中辨明病因、病位以及玄府闭塞的程度后,可用风药从多角度开通生殖轴玄府,达到理想的治疗效果。外感风寒型月经病祛风以通玄,常用药物有麻黄、桂枝、荆芥、防风、生姜等;气郁玄府型月经病理气以通玄,常用药物有柴胡、枳壳、青皮、香附、木香等;血瘀型月经病活血以通玄,常用药物有桂枝、川芎、荆芥、刺蒺藜、白芷、细辛、羌活、葛根等;痰湿型月经病化湿以通玄,常用药物有升麻、葛根、柴胡、羌活、独活等;虚实相兼型玄府病变补虚以通玄,常用药物有羌活、独活、防风、白芷等。通过正确的药物配伍,在月经病中灵活运用风药,可获良效。

国医大师夏桂成治疗不孕症学术思想探析

国医大师夏桂成教授从“肾主生殖”理论出发,认为不孕症总体病机为肾气不足,冲任气血失调,故治法多主张补肾调冲任。排卵障碍性不孕症、多囊卵巢综合征型不孕症、卵巢功能不全性不孕症、黄体功能不全性不孕症、高催乳素血症不孕症、输卵管性不孕症、免疫性不孕症等发病机理主要在于肾阴亏虚,气血阴阳失调。夏老根据多年的临床经验以及妇科病生理特点总结出月经周期节律调节法,将女性月经周期分成7个阶段,分别是行经期、经后初期、经后中期、经后末期、经间期、经前前半期和经前后半期,根据不同时期的生理特点确定治则及方药,还独创心-肾-子宫生殖轴理论,注重调节肝脾气机、疏畅月经来潮。另外,夏老认为,精神因素不仅直接影响排卵,还会导致免疫力下降,临床治疗中重视阴阳相合,提倡男女双方同治同调。

多玛绵羊繁殖季节与非繁殖季节生殖激素水平及其受体表达水平分析

为研究多玛绵羊生殖激素浓度和下丘脑-垂体-卵巢轴上生殖激素受体表达水平在发情季节与非发情季节的差异情况,使用ELISA测定了60只多玛绵羊发情与非发情季节血清中促性腺激素释放激素(GnRH)、促卵泡素(FSH)、促黄体素(LH)和促甲状腺激素(TSH)的浓度,下丘脑-垂体上促性腺激素释放激素受体(GnRHR),卵巢上促卵泡素受体(FSHR)和促黄体生成素受体(LHR),以及子宫内膜上孕激素受体(PGR)和雌激素受体(ER)的表达水平。结果显示,多玛绵羊血清中GnRH、FSH、LH在非发情季节显著低于发情季节(P<0.05),下丘脑Kisspeptin与KISS1R在发情季节显著增加(P<0.05);下丘脑-垂体组织中GnRHR基因,卵巢上FSHR和LHR基因以及子宫内膜中ER和PGR基因的表达水平在发情季节显著高于非发情季节(P<0.05)。发情季节卵巢切片上发育卵泡的数量显著多于非发情季节(P<0.05);发情季节FSHR、LHR阳性细胞密度显著高于非发情季节(P<0.05);发情季节ER和PGR阳性腺上皮细胞显著高于非发情季节(P<0.05),但子宫PGR阳性基质细胞在发情季节和非发情季节之间没有显著性差异(P>0.05)。由此可见,多玛绵羊下丘脑-垂体-卵巢/子宫中主要生殖激素及其受体的表达水平在发情季节高于非发情季节。

基于“脑-心-肾-精室”轴辨证论治男性不育症

基于“脑-心-肾-精室”轴理论辨证论治男性不育症,是对《黄帝内经》肾主生殖理论的补充。在男性不育症的治疗中,将脑、心、肾、精室作为一个整体,将“肾”作为男性不育症辨证治疗过程的核心,将“脑心失调”作为男性不育症发病的重要原因,认为“精室失用”为男性不育症发病的最终环节,是对当代男性不育症中医诊治体系的补充。在“脑-心-肾-精室”轴理论的指导思想下,男性不育症的治疗应以精血为基础,以督脉为纽带,脑、心、肾三者贯通上下,彼此衔接,相互影响。正常情况下,脑、心、肾三者协调有度,发挥肾主生殖、脑心共主神明,从而维持精室的正常开阖疏泄。一旦某一环节出现问题,则最终作用于精室,影响男性的生殖系统。应用“脑-心-肾-精室”轴治疗男性不育症,应注重肾主生殖的核心地位,侧重脑心同治,以调和精室,从而达到“心身同治,整体与局部同调”的目的。

罗颂平从中医生殖轴论治卵巢功能衰退不孕症经验

总结罗颂平教授治疗卵巢功能衰退不孕症的临证经验。罗颂平教授基于“肾-天癸-冲任-胞宫”中医生殖轴学说,认为脾肾虚弱、天癸不充、冲任不盛为卵巢功能衰退不孕症的病机之本,患者肾虚常夹杂肝郁、血瘀。防治卵巢功能衰退引起的不孕,当立足于调“肾-天癸-冲任-胞宫”生殖轴,着重从生殖轴之源头(肾)论治,以补肾为根本大法,且需补脾益后天以资先天;补肾填精、健脾养胃以调冲任,防天癸早竭,并兼顾疏肝、活血;同时提倡配合服用膏方“养血育麟膏”,针药结合,药食并用,内外合治。综合运用多种特色中医疗法以使肾精足,天癸盛,脏腑相和,气血冲任通畅,胞宫充盈,而后方可孕育子嗣。

基于天癸理论探讨干眼的发病机制

干眼是多因素导致的慢性眼表疾病,与下丘脑-垂体内分泌系统密切相关。天癸与下丘脑-垂体-性腺轴关联。基于天癸理论探讨天癸与目生理联系、天癸与干眼之间的病机联系,认为天癸衰少所致冲任虚瘀、目络阻滞是干眼发病的重要因素;天癸不足所致肝肾藏泄失衡为干眼的病机本质;天癸阴阳失衡所致目阴阳失调为病机关键。提出疏导冲任,活血化瘀为治疗干眼之要;补益肝脾肾,益源生癸为治疗干眼之本;药性相平,适配天癸阴阳为治疗干眼用药准则。以期基于天癸理论为干眼治疗提供参考与借鉴。

基于海派心-性生殖轴探讨男性勃起功能障碍的中医辨证思路

海派男科源于上海周氏男科,其创始人为上海市名中医、著名中医泌尿男科专家周智恒教授。其在周智恒教授的学术思想指导下经过不断发展,对于多种男性不育、性功能障碍疾病有着丰富的诊治经验。通过对传统中医知识理论的不断总结,并结合多年以来的临床诊治经验,周智恒教授在男性生殖轴的构建中创新性地提出了一核三基理论,即以心神(心-脑)为核心,肝、肾、脾-胃为基础,各脏腑之间以气血经脉为联系,重视心神在性-生殖过程中的主导地位。在男性勃起功能障碍的辨证论治中,与传统医家多从肝肾论治不同,周智恒教授主张以心养“性”、形神共治,海派心-性生殖轴的构建丰富了中医男科基础理论,拓展了中医在男性疾病中的诊疗思路。

陈霞教授论治排卵障碍型不孕症经验撷要

不孕是困扰育龄期女性及其家庭常见的身心疾病。女性不孕的原因有很多,其中因病理所致多为排卵障碍型不孕,故促排助孕为治疗的关键。排卵障碍型不孕症是指由于女性双侧卵巢不能正常排卵,导致无法正常受孕的病证。陈霞教授认为,排卵障碍型不孕症的发病原因为肾虚,肾虚则精血亏虚,冲任不盛,乃至经乱,甚则难以摄精受孕,而肝主藏血,调冲任,脾为后天之本,化生精血,继发肝郁脾虚,兼夹痰湿、瘀血等因素。肾虚则癸水不足,肾-天癸-冲任-胞宫生殖轴功能紊乱系主要病机,治疗当以补肾为主,兼顾疏肝健脾,佐以化痰祛湿、理气活血等。临床上可根据患者的月经周期分期论治,调经促排,种子育胎。药物治疗的同时再结合心理疏导,在临床上多有成效,文章通过案例,介绍陈霞教授治疗排卵障碍型不孕症经验,以期为临床提供参考。

孕期和哺乳期环境剂量氯氰菊酯暴露对子代雄性小鼠青春期启动的影响

氯氰菊酯(cypermethrin,CP)是一种应用广泛的拟除虫菊酯类农药,作为潜在的环境污染物和内分泌干扰物,其围产期暴露对子代具有一定的毒性作用。为探究孕期和哺乳期氯氰菊酯环境剂量暴露对子代雄性小鼠青春期启动的影响,将ICR小鼠在妊娠第6天至子代出生后(postnatal day,PND)第21天,暴露于0、6.7、20和60μg·kg^(-1)·d^(-1)氯氰菊酯,观察子代雄性小鼠青春期启动情况,同时分别检测PND22小鼠下丘脑、垂体、睾丸组织中GnRH、KISS-1、CGα、LHβ、FSHβ、StAR和CYP1A1的表达水平以及血清中促性腺激素释放激素、卵泡刺激素、黄体生成素和睾酮的含量。检测PND21 ICR小鼠下丘脑和睾丸组织体外暴露于0、6.7、20和60μg·L^(-1)氯氰菊酯后丙二醛、总谷胱甘肽、NO含量和总超氧化物歧化酶活性。结果表明,在60μg·kg^(-1)·d^(-1)的氯氰菊酯暴露剂量下,子代雄性小鼠青春期启动日龄减少(P<0.01);20~60μg·kg^(-1)·d^(-1)显著诱导促性腺激素释放激素、黄体生成素和睾酮分泌(P<0.05);6.7~60μg·L^(-1)体外暴露24 h会对下丘脑和睾丸组织产生氧化损伤。孕期和哺乳期氯氰菊酯环境剂量暴露可导致子代雄性小鼠青春期启动提前,下丘脑-垂体-睾丸轴相关激素分泌总体上调。本研究结果为准确、全面评估拟除虫菊酯类杀虫剂的环境安全与健康风险提供科学依据和理论基础。

从经脉脏腑角度探讨痛经病位胞宫与经穴效应的关系

目的:通过对痛经病位胞宫及其经脉脏腑关系和临床治疗选穴等相关文献进行整理和总结,进而了解胞宫与经脉脏腑经穴的关系。方法:以"痛经""胞宫"为主题词,检索中国核心期刊网络出版总库(CNKI)(1981年1月—2013年11月)83篇。结果:在生理上,生殖轴"肾-天癸-冲任"使胞宫与经脉(冲、任、督、带)、脏腑(肾、肝、脾、胃、心、肺)紧密联系;在病理上,痛经的发病与胞宫相关经脉、脏腑之间关系密切;在治疗上,相关经穴三阴交是痛经治疗的常用穴之一。结论:胞宫与经脉、脏腑密切相关。以胞宫为切入点,分析胞宫与经穴的经脉脏腑关系,为临床上痛经的选穴和治疗提供理论依据。