原始卵泡发育启动的影响因素

原始卵泡发育的启动是卵泡发育过程中的一个重要阶段。H1foo等基因可能对该过程具有调节作用。生长因子可能促进原始卵泡向初级卵泡的转化。笔者还介绍了2种用于研究原始卵泡活化的模型.     

TGF-β家族成员调控家禽卵泡发育的研究进展及展望

与哺乳动物不同,家禽的卵泡发育无明显发情周期,其卵泡发育遵循严格的等级发育体系。禽类卵泡的等级发育是一个复杂的调节过程,受卵泡细胞内外的内分泌激素、自分泌/旁分泌因子的共同调节。促卵泡刺激素(Follicle stimulating hormone,FSH)和促黄体激素(Luteinizing hormone,LH)在调控卵泡发育、卵母细胞成熟和排卵中起着重要的作用。此外,局部产生的生长因子如转化生长因子β超家族(Transforming growth factor superfamily,TGF-β)成员,包括抗缪勒氏激素(Anti-Müllerian hormone,AMH)、骨形态蛋白家族(Bone morphogenetic proteins,BMPs)、抑制素(Inhibin)和激活素(Activin)等,与促性腺激素一起协同调控卵泡的生长发育、卵母细胞的成熟等过程。文章综述了TGF-β家族成员,包括AMH、BMPs、抑制素、激活素在家禽卵泡发育中的作用及其未来的研究方向。     

哺乳动物原始卵泡的形成和发育及影响因素

原始卵泡形成和发育是成年动物卵巢发挥最优生产潜能的重要事件,在卵巢发育过程中起着至关重要的作用,然而卵巢发育相关研究中,人们更多地关注生长卵泡而忽视了原始卵泡。研究表明,不同物种的哺乳动物原始卵泡形成时间存在差异,影响原始卵泡形成和发育的主要因素有信号通路、生长因子、转录因子以及激素。本文就哺乳动物原始卵泡形成和发育以及影响因素作一综述。     

抑制素-活化素-卵泡抑素系统研究进展

抑制素、活化素和卵泡抑素主要由垂体细胞和卵巢颗粒细胞分泌,是细胞转化生长因子超家族的成员.抑制素-活化素-卵泡抑素系统作为卵巢卵泡内局部调节因子,通过内分泌机制调节垂体卵泡刺激素的分泌,通过旁分泌和自分泌的机制调节卵巢卵泡的发育、闭锁和黄体化过程,进而调节动物的生殖活动.本文综述了抑制素-活化素-卵泡抑素系统的结构特性...     

卵泡发育的激素调节研究进展

卵泡的发育经历了早期的发育、有腔卵泡的生长、优势卵泡的选择以及卵泡成熟排卵等过程。在一个发情周期中，数以万计的原始卵泡发育到排卵阶段时排卵数仅占原始卵泡总数的0.1%-0.2%，绝大数与产仔率有着极大的正相关，要提高产仔率就要防止卵泡闭锁，增加排卵数。而激素调节伴随着卵泡发育的始终，其中垂体促性腺激素和甾体激素可促进卵母细胞的生长、卵母细胞的增殖和卵泡腔的形成，在卵泡发育的过程中起着至关重要的作用。本文主要就促性腺激素、甾体激素和抑制素在卵泡发育中调节作一综述。     

Bmp/Smad信号通路及其在哺乳动物卵巢发育中的作用

开展绵羊多羔性状基因的研究对于揭示其分子调控机制和提高绵羊繁殖力具有重要意义。骨形态发生蛋白(BMPs)为转化生长因子-β(TGF-β)超家族成员,与哺乳动物繁殖活动密切相关。研究表明,BMPs可促使原始卵泡向次级卵泡转化,对哺乳动物卵巢颗粒细胞增殖、生殖激素的合成和分泌以及卵母细胞成熟和排卵等方面起重要调节作用,而BMPs发挥功能主要依赖于经典的Bmp/Smad信号通路。本文就Bmp/Smad信号通路成员的表达、对早期胚胎发育的影响以及在哺乳动物卵巢发育中的作用等方面的研究进行总结,以期为进一步研究BMPs及其信号通路的调控机制提供参考。     

哺乳动物优势卵泡选择的研究进展

哺乳动物优势卵泡选择是卵泡发育过程中的关键环节,只有被选择的优势卵泡在适当条件下才会排卵,阐明优势卵泡选择机制具有重要意义.文章对影响优势卵泡选择的因素加以探讨,涉及到优势卵泡选择过程中促性腺激素浓度的变化、雌二醇浓度的增加、合成类固醇酶的表达和胰岛素生长因子系统.目前,优势卵泡选择的机制还未完全被阐明,除胰岛素样生长因子以外的生长因子、激活素/抑制素系统和信号转导途径等在卵泡选择中的作用还需进一步研究.     

小白鼠卵泡壁发育的形态学研究

选择性成熟的纯种小白鼠，用ＦＳＨ和ｈｃＧ处理，取其卵巢，制成光学切片，显微镜下观察卵泡壁发育的形态学变化过程。胚胎阶段发育而来的原始卵泡的扁平细胞钭发育为颗粒层细胞，颗粒细胞最初在单层上增殖细胞的数量；卵泡膜在初级卵泡在初期就开始形成，是由卵巢基质中的扁平样细胞发育而来；卵泡膜中的血管是由卵巢基质中血管伸入形成，在初级卵泡刚开始形成时就开始生长发育。     

水牛腔前卵泡的分布及形态学研究

用常规石蜡切片法研究水牛卵泡在卵巢中的分布规律与结构特征。结果表明各级卵泡的分布具有明显的区域性;原始卵泡位于卵巢皮质的最外层,形成原始卵泡层,初级卵泡位于皮质的中层,次级卵泡位于富含血管的皮质最内层;原始卵泡、初级卵泡和次级卵泡的直径分别为(36.9±7.7)μm、(48.7±8.9)μm和(91.9±27.3)μm,与之对应卵母细胞的直径分别为(19.6±6.0)μm、(27.3±7.1)μm和(49.1±17.4)μm;原始卵泡和初级卵泡的颗粒细胞数为(10.8±2.3)个和(18.1±3.1)个;次级卵泡含有2~6层颗粒细胞,2~4层的颗粒细胞分布不均。     

母猪的生殖生理特点

1内分泌和发情周期许多激素的分泌控制着发情周期,这些激素由大脑、卵巢和子宫分泌,并且通过血液循环分布全身。促卵泡激素(FSH)和促黄体生成素(LH)是由大脑分泌的。FSH控制着卵巢中卵泡的发育过程,LH促使卵泡破裂并释放卵细胞,控制着黄体的发育以及孕激素的分泌。卵巢中的卵泡可以分泌雌激素,而黄体可以产生孕激素。孕激素可以保证子宫的内环境适宜胎儿生长。另外,孕激素还控制着     

哺乳动物原始卵泡形成与发育的研究进展

在大多数雌性哺乳动物中,早期原始卵泡的形成主要包括3个过程：原始生殖细胞的迁移、生殖细胞减数分裂和生殖细胞巢破裂。原始卵泡形成与发育过程涉及到诸多因子和信号通路的调节作用,且原始卵泡库的大小及储备能力将决定雌性动物终生生殖能力。本文就参与原始卵泡形成和发育过程中的因子和信号通路作一综述,旨在深入了解参与原始卵泡形成与发育的细胞和分子机制,为维持原始卵泡库及促进原始卵泡激活提供研究思路。     

Regulation of secondary follicle growth by theca cells and insulin-like growth factor 1

Ovaries contain follicles at various stages of development, including primordial, primary, secondary, antral and Graafian follicles. Although the growth of these follicles is controlled to maintain regular ovulation, the mechanism through which this occurs remains unclear. In our study, we found that the growth rate of cultured secondary follicles separated from mice ovaries differed between follicles. After 4 days of culture, the size of some secondary follicles was markedly increased, while that of others had either slightly increased, remained unchanged or shrunk. We compared the expression levels of growth factors between these secondary follicles and found that the growth rate of cultured secondary follicles correlated with the expression level of insulin-like growth factor 1 (Igf1) mRNA. Igf1 mRNA expression level in secondary follicles containing theca cells was higher than that in secondary follicles without theca cells, and the granulosa cell proliferation around follicles containing theca cells was increased. Furthermore, an IGF1 inhibitor also inhibited the granulosa cell proliferation, and administration of IGF1 to secondary follicles without growth promoted granulosa cell proliferation. These results indicated that the theca cells of secondary follicles induced the expression of IGF1 and promoted the follicle growth.     

山羊卵巢无腔卵泡的体外发育

在三维琼脂凝胶培养体系中 ,山羊无腔卵泡的生长模式类似于体内。在一定培养时间内能善为保持其完整的立体结构和形态。原始卵泡能在体外启动 ,并得到一定程度的生长。初级卵泡能发育为次级卵泡 ,次级卵泡发育为有腔卵泡。卵泡在体外发育过程中 ,表现出了明显的优势化。本试验首次初步揭示了山羊无腔卵泡的体外发育基本过程和规律。     

哺乳动物原始卵泡体外培养与激活调控研究进展

随着体外受精、克隆与转基因动物等基础研究快速发展,对卵母细胞的需求越来越多,科学家们不得不寻求能够获得大量优质卵母细胞的新途径。原始卵泡作为生长卵泡的来源,其初始容量影响哺乳动物的繁殖性能,是整个雌性生殖期中各阶段卵泡及卵子发育的源头。哺乳动物的卵巢在出生时由一定数量的卵泡组成,大多数原始卵泡处于休眠状态,只有极少数的原始卵泡被激活并进入生长卵泡池中。因此合理开发卵巢里尚未激活的原始卵泡对提高动物繁殖率、加速优良牛种的遗传改良、阐明动物卵泡发生的分子机理具有重要意义。本文将目前哺乳动物原始卵泡体外激活的国内外进展做一综述,为研究动物和人类卵泡激活的生物学过程提供理论基础。     

Rapamycin maintains the primordial follicle pool and protects ovarian reserve against cyclophosphamide-induced damage

Any abnormal activation of primordial follicles and subsequent depletion can irreversibly diminish the ovarian reserve, which is one of the major chemotherapy-induced adverse effects in young patients with cancer. Herein, we investigated the effects of rapamycin on the activation and development of ovarian follicles to evaluate its fertility-sparing therapeutic value in a cyclophosphamide (CTX)-treated mouse model. Based on ovarian histomorphological changes and follicle counting in 50 SPF female C57BL/6 mice, daily administration of 5 mg/kg rapamycin for 30 days was deemed an ideal dosage and duration for administration in subsequent experiments. Compared with the control group, rapamycin treatment inhibited the activation of quiescent primordial follicles, with no obvious side effects observed. Finally, 48 mice were randomly divided into four groups: control, rapamycin-treated, cyclophosphamide-treated, and rapamycin intervention. Body weight, ovarian histomorphological changes, number of primordial follicles, DDX4/MVH expression, apoptosis of follicular cells, and expression of apoptosis protease-activating factor (APAF)-1, cleaved caspase 3, and caspase 3 were monitored. Co-administration of rapamycin reduced primordial follicle loss and the development of follicular cell apoptosis, thereby rescuing the ovarian reserve after CTX treatment. On analyzing the mTOR signaling pathway, we observed that rapamycin significantly decreased CTX-mediated overactivation of mTOR and its downstream molecules. These findings suggest that rapamycin exhibits potential as an ovarian-protective agent that could maintain the ovarian primordial follicle pool and preserve fertility in young female patients with cancer undergoing chemotherapy.     

Regulation of primordial follicle formation,dormancy, and activation in mice

In female reproduction, the oocyte number is limited after birth. To achieve a continuous ovulatory cycle, oocytes are stored in primordial follicles. Therefore, the regulation of primordial follicle dormancy and activation is important for reproductive sustainability, and its collapse leads to premature ovarian insufficiency. In this review, we summarize primordial follicle development and the molecular mechanisms underlying primordial follicle maintenance and activation in mice. We also overview the mechanisms discovered through in vitro culture of functional oocytes, including the establishment of primordial follicle induction by environmental factors, which revealed the importance of hypoxia and compression by the extra cellular matrix (ECM) for primordial follicle maintenance in vivo.     

Promotion of ovarian follicular development by injecting vascular endothelial growth factor (VEGF) and growth differentiation factor 9 (GDF-9) genes

Ovarian follicular development in mammals is the complex process including endocrine, paracrine and autocrine. There is the development of four basic stages of ovarian follicles, i.e. the primordial, primary, secondary and tertiary or Graafian follicles. There are few blood vessels in the cortical area where primordial and primary follicles are assembled. The development of these follicles is stimulated by oocytes derived factor including growth differentiation factor 9 (GDF-9) or bone morphogenetic protein 15 (BMP-15). Porcine GDF-9 complementary DNA (cDNA) cloned, and then injected its gene into the ovary in gilts. The injection of porcine GDF-9 gene resulted in an increase in the number of primary, secondary and tertiary follicles, concomitant with a decrease in the number of primordial follicles, indicating that exogenous GDF-9 can promote early folliculogenesis in the porcine ovary. On the other hand, the development of antral follicles is associated with increased density of blood vessels within the theca cell layers surrounding the follicles. A recent study reported that vascular endothelial growth factor (VEGF) play an important role in the process of thecal angiogenesis during follicular development. To investigate whether additional induction of thecal angiogenesis would support subsequent follicular development, miniature gilts were directly injected VEGF gene into the ovary. Injection of VEGF gene increased the levels of mRNA expression of VEGF 120 and VEGF 164 isoforms in the granulosa cells and VEGF protein contents in the follicular fluid. The number of preovulatory follicles and the capillary density in the theca interna increased significantly in the ovaries injected with VEGF gene compared with those treated with eCG alone, indicating that the regulation of thecal angiogenesis during follicular development is a very important factor in the development of ovulatory follicles. This technique may be an innovative technique for enhanced induction of follicular development in the ovary through gene and hormonal treatment, which may lead to prevention of infertility caused by ovarian dysfunction.     

Expression Pattern of Vascular Endothelial Growth Factor in Canine Folliculogenesis and its Effect on the Growth and Development of Follicles after Ovarian Organ Culture

In this study, the expressions of VEGF in dog follicles were detected by immunohistochemistry and the effects of VEGF treatment on the primordial to primary follicle transition and on subsequent follicle progression were examined using a dog ovary organ culture system. The frozen‐thawed canine ovarian follicles within slices of ovarian cortical tissue were cultured for 7 and 14 days in presence or absence of VEGF. After culture, the ovaries were fixed, sectioned, stained and counted for morphologic analysis. The results showed that VEGF was expressed in the theca cells of antral follicles and in the granulosa cells nearest the oocyte in preantral follicle but not in granulosa cells of primordial and primary follicles; however, the VEGF protein was expressed in CL. After in vitro culture, VEGF caused a decrease in the number of primordial follicles and concomitant increase in the number of primary follicles that showed growth initiation and reached the secondary and preantral stages of development after 7 and 14 days. Follicular viability was also improved in the presence of VEGF after 7 and 14 days in culture. In conclusion, treatment with VEGF was found to promote the activation of primordial follicle development that could provide an alternative approach to stimulate early follicle development in dogs.     

The effect of bpV(HOpic) on in vitro activation of primordial follicles in cultured swine ovarian cortical strips

The vanadate‐derivative dipotassium bisperoxo (5‐hydroxy‐pyridine‐2‐carboxylic) oxovanadate (V) (bpV(HOpic)), a pharmacological inhibitor of phosphatase and tensin homolog (PTEN), has been used in ovarian follicle culture systems for activation of follicular growth in vitro and suggested to be responsible for primordial follicle survival through indirect Akt activation. For pig ovarian tissue, it is still not clear which culture medium needs to be used, as well as which factors and hormones could influence follicular development; this also applies to bpV(HOpic) exposure. Therefore, ovarian cortical strips from pigs were cultured in 1 µM bpV(HOpic) (N = 24) or control medium (N = 24) for 48 hr. Media were then replaced with control medium and all tissue pieces incubated for additional 4 days. The strips were embedded in paraffin for histological determination of follicle proportions at the end of the culture period and compared to histological sections from tissue pieces without cultivation, which had been embedded right after preparation; comparison of healthy follicles for each developmental stage was performed to quantify follicle survival and activation. After 6‐day culture, follicle activation occurred in tissue samples from both cultured groups but significantly more follicles showed progression of follicular development in the presence of 1 µM bpV(HOpic). The amount of non‐vital follicles was not significantly increased during cultivation. BpV(HOpic) affects pig ovarian follicle development by promoting the initiation of follicle growth and development, similar as in rodent species and humans.     

Growth of primordial oocytes in neonatal and adult mammals

Mammalian ovaries are endowed with a huge number of small oocytes (primordial oocytes) in primordial follicles. A small number of primordial oocytes start to grow, while others remain quiescent. Little is known about the mechanism regulating the activation of primordial oocytes. Recently, we found that primordial follicles in mature cows and prepubertal pigs took longer to initiate growth in xenografts compared with those in neonatal animals. We think that primordial oocytes in adult mammals are different from those in neonatal mammals. In this review, we summarize the results regarding the activation of primordial oocytes in neonatal and adult ovaries of different species and propose a model in which ovaries of neonatal mammals contain a mixed population of both quiescent and activated primordial oocytes, while almost all primordial oocytes are quiescent in adult females. The dormancy of primordial oocytes may be required to reserve the non-growing oocyte pool for the long reproductive life in mammals. FOXO3 is considered one of the molecules responsible for the dormancy of primordial oocytes in adult ovaries. These quiescent primordial oocytes are activated, perhaps by certain mechanisms involving the interaction between stimulatory and inhibitory factors, to enter the growth phase.