Regulation of Folliculogenesis During Ovarian Recrudescence

卵巢复发过程中卵泡发生的调节

• 批准号: 8998649
• 负责人: KELLY Ansley YOUNG
• 金额: $ 11.04万
• 依托单位: CALIFORNIA STATE UNIVERSITY LONG BEACH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8998649
• 关键词: Ablation; Adult; Affect; Antral; Apoptosis; Breeding; CCND2 gene; Complex; Data; Development; Developmental Process; Embryo; Endocrine; Estradiol; Estrus; Exposure to; Female; Fertility; Follicle Stimulating Hormone; Future; Gene Expression; Genomics; Goals; Gonadal structure; Gonadotropins; Growth; Hamsters; Hour; Immunohistochemistry; In Vitro; Individual; Insulin-Like Growth Factor I; Interruption; Investigation; KISS1 gene; KITLG gene; Knowledge; Lead; Light; Longevity; Luteinizing Hormone; Maintenance; Measurement; Mediating; Menopause; Modeling; Neonatal; Oocytes; Ovarian; Ovary; Ovulation; Parents; Periodicity; Phodopus sungorus; Photoperiod; Plasma; Premature Ovarian Failure; Process; Prolactin; Proteins; Recrudescences; Regulation; Reproduction; Reproductive Health; Risk; Role; Seasons; Siberian Hamster; Signal Transduction; Staging; System; Thyroid Hormones; Time; Tissues; Transcript; Woman; Work; base; corpus luteum; day length; folliculogenesis; in vivo; inhibitor/antagonist; innovation; mRNA Expression; novel; offspring; public health relevance; reproductive; reproductive function; reproductive senescence; research study; restoration; screening; transcriptome; young adult

 DESCRIPTION (provided by applicant): Understanding ovarian function in adults is a requirement to maximize female reproductive health, including providing women sufficient options in fertility regulation and maintenance. When ovarian function fails in young adult women, a condition known as premature ovarian failure (POF), their future fertility is at risk. However, most studies that examine how follicle development can be initiated in the ovary do so in neonatal or peri-pubertal females, not adults. Siberian hamsters (Phodopus sungorus) serve as an ideal model for investigating how a non-functional adult mammalian ovary can resume activity, because exposing these hamsters to different photoperiods, the number of hours of light per day, can turn ovarian function "on" or "off". We have shown that exposure of adult Siberian hamsters to long day photoperiod (LD; 16 hours of light per day, 8 hours of dark per day) maintains ovarian function, whereas exposure to inhibitory short day lengths (SD, 8L:16D) for 14 weeks induces ovarian regression. Subsequent transfer of photo-regressed females to LD stimulates ovarian recrudescence, a process that restarts the non-cycling ovaries. Multiple mechanisms regulate these transitions in ovarian function, although how folliculogenesis actually resumes during recrudescence has not been explored. This proposal hypothesizes that signaling factors promoting folliculogenesis are 1) present in Siberian hamster ovaries and regulated by photoperiod, and 2) differentially regulated by non-gonadotropin factors and FSH in regressed and recrudescing ovaries. The aims of this proposal first use a systematic genomic screening of adult ovaries to identify transcripts up- and down- regulated during recrudescence. Next, an in vivo ablation and restoration of FSH during photo-stimulation examines FSH independent factors triggered by photo-stimulation that may restore follicle growth. Finally, an in vitro culture system will be used to expose recrudescing ovaries to inhibitors of key folliculogenic factors (e.g., AMH, IGF-1, KitL, FoxO3, Src), determining individual contributions of these factors to recrudescence. Culture of regressed ovaries with factors known to systemically mediate photoperiodic change (prolactin, thyroid hormone, kisspeptin) will follow, examining non-gonadotropin triggers of ovarian recrudescence to determine if these factors potentially "prime" the regressed ovary for rapid return to function. Importantly, while signaling factors have been broadly assessed during early stages of folliculogenesis, particularly in peri-pubertal females, no studies have done this in adult tissue with a naturally quiescent ovary as it resumes function. Taken together, the work proposed here will provide a better understanding of the how a non-cycling ovary returns to function, and how folliculogenesis is restored in the adult ovary. Our unique model may yield discovery of novel signaling factors critical for restoration of folliculogenesis, particularly at its early stages. This knowledge is fundamental to our understanding of fertility, considering that follicle activation occurs across the reproductive lifespan, not just during ovarian development.

 描述（由适用提供）：了解成年人的卵巢功能是最大化女性生殖健康的必要条件，包括为妇女提供足够的生育和维持方案。当年轻妇女（一种称为早产卵巢衰竭（POF））的年轻妇女的卵巢功能失败时，她们的未来生育能力处于危险之中。但是，大多数研究如何在卵巢中启动卵泡发育的大多数研究是在新生儿或青春期女性而不是成年人中进行的。西伯利亚仓鼠（Phodopus sungorus）是研究非功能性的成年哺乳动物卵巢如何恢复活动的理想模型，因为将这些仓鼠暴露于不同的光周期，每天的光小时数量，可以使卵巢功能变成“或” OFF。我们已经表明，成年西伯利亚仓鼠暴露于漫长的光周期（LD；每天16小时的光线，每天8小时的黑暗小时）保持卵巢功能，而暴露于抑制性短期长度（SD，8L：16D）14周，可引起卵巢回归。随后将光的女性转移到LD的转移会刺激卵巢复发，这一过程重新开始了非循环卵巢。多种机制在卵巢功能中调节了这些转变，尽管尚未探索卵泡发生在复发过程中的实际恢复。该提议假设促进卵泡发生的信号因子是1）在西伯利亚仓鼠卵巢中存在，并受到光周期调节，以及2）2）在回归和繁殖的卵巢中受非gonadotropin因子和FSH的差异调节。该提案的目的首先使用对成年卵巢进行系统的基因组筛查，以识别复发过程中调节的上下调节的转录本。接下来，在照片刺激检查期间，FSH的体内消融和恢复FSH独立因素是由照片刺激触发的，可能会恢复叶片的生长。最后，一个 体外培养系统将用于暴露于关键卵泡因子抑制剂（例如AMH，IGF-1，KITL，FOXO3，SRC）的抑制剂，确定这些因素对复发性的贡献。卵巢回落的培养物将随后发生系统介导的光生碘变化（催乳素，甲状腺植物，亲吻蛋白）的培养，以检查卵巢繁殖的非冈杜氏体触发触发器是否可能“潜在地”回归的卵巢“素数”，以确定这些因素是否有可能“素数”以快速恢复到功能。重要的是，虽然在卵泡发生的早期，特别是在骨周围女性的早期阶段，对信号传导因素进行了广泛的评估，但由于它恢复功能，因此在成人组织中没有研究在成人组织中进行此研究。综上所述，这里提出的工作将更好地了解非循环卵巢如何回报功能，以及如何在成年卵巢中恢复卵泡发生。我们独特的模型可能会发现新的信号传导因子对于恢复卵泡发生至关重要的，尤其是在早期阶段。这些知识对 我们对生育能力的理解，考虑到整个复制品发生叶片激活 寿命，不仅是在卵巢发展期间。