慢性束縛壓力誘導小鼠卵巢中原始卵泡的過度活化

我們也證明壓力(stress,海水+開刀四週後)真的促使鰻魚(同一 鰻魚開刀前後)初級卵細胞發育，但固定後直徑 60 um 以下的卵不為所動...

PLoS One. 2018; 13(3): e0194894.

Published online 2018 Mar 30. doi:  10.1371/journal.pone.0194894

 PMCID: PMC5877864

PMID: 29601583

Chronic restraint stress induces excessive activation of primordial follicles in mice ovaries

(慢性束縛壓力誘導小鼠卵巢中原始卵泡的過度活化)

Abstract

Chronic stress is an important factor influencing people’s health. It usually causes endocrinal disorders and a decline in reproduction in females. Although studies of both human and animals suggest a detrimental effect of stress on reproduction, the influence of chronic stress on the ovarian reservation and follicular development is still not clear. In this study, a chronic restraint stress (CRS) mouse model was used to investigate the effect of stress on ovarian reservation and follicular development and explore the underlying mechanism. In this study, after 8 weeks of CRS, primordial follicles were excessively activated in the ovaries of the CRS group compared with the control group. Further results showed that the activation of primordial follicles induced by CRS was involved in the increasing expression level of Kit ligand and its receptor Kit and the activation of phosphatidylinositol 3-kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN)/protein kinase B (Akt) pathway. The corticotropin-releasing hormone (CRH) is a neuropeptide released due to stress, which plays an important role in regulating follicle development. A high level of serum CRH was detected in the CRS mouse model, and the real-time polymerase chain reaction assay showed that the mRNA level of its main receptor CRHR1increased in the ovaries of the CRS mouse group. Moreover, 100nM CRH significantly improved the activation of primordial follicles in newborn mouse ovaries in vitro. These results demonstrated that CRS could induce immoderate activation of primordial follicles accompanied by the activation of Kit-PI3K signaling, in which CRH might be an important endocrine factor.

慢性壓力是影響人們健康的重要因素。它通常會導致內分泌失調和女性生殖能力下降。儘管對人和動物的研究都表明壓力對生殖的不利影響，但慢性壓力對卵巢保留和卵泡發育的影響仍不明確。本研究採用慢性束縛應激（CRS）小鼠模型研究應激對卵巢保留和卵泡發育的影響，並探討其潛在機制。在該研究中，在CRS 8週後，與對照組相比，CRS組的卵巢中的原始卵泡過度活化。進一步的結果表明，CRS誘導的原始卵泡的活化參與了Kit配體及其受體Kit的表達水平的增加和10號染色體上缺失的磷脂酰肌醇3-激酶（PI3K）/磷酸酶和張力蛋白同源物的激活（PTEN）/蛋白激酶B（Akt）途徑。促腎上腺皮質激素釋放激素（CRH）是由於壓力釋放的神經肽，其在調節卵泡發育中起重要作用。在CRS小鼠模型中檢測到高水平的血清CRH，並且實時聚合酶鏈反應測定顯示其主要受體CRHR1的mRNA水平在CRS小鼠的卵巢中增加。此外，100nM CRH顯著改善了新生小鼠卵巢體外原始卵泡的活化。這些結果表明，CRS可誘導原始卵泡的無活性激活，伴隨著Kit-PI3K信號的激活，其中CRH可能是一種重要的內分泌因子。

PLoS One. 2013 Oct 10;8(10):e77396. doi: 10.1371/journal.pone.0077396. eCollection 2013.

The pituitary gland of the European eel reveals massive expression of genes involved in the melanocortin system.

Ager-Wick E1, Dirks RP, Burgerhout E, Nourizadeh-Lillabadi R, de Wijze DL, Spaink HP, van den Thillart GE, Tsukamoto K, Dufour S, Weltzien FA, Henkel CV.

Author information

Abstract

Hormones secreted from the pituitary gland regulate important processes such as development, growth and metabolism, reproduction, water balance, and body pigmentation. Synthesis and secretion of pituitary hormones are regulated by different factors from the hypothalamus, but also through feedback mechanisms from peripheral organs, and from the pituitary itself. In the European eel extensive attention has been directed towards understanding the different components of the brain-pituitary-gonad axis, but little is known about the regulation of upstream processes in the pituitary gland. In order to gain a broader mechanistic understanding of the eel pituitary gland, we have performed RNA-seq transcriptome profiling of the pituitary of prepubertal female silver eels. RNA-seq reads generated on the Illumina platform were mapped to the recently assembled European eel genome. The most abundant transcript in the eel pituitary codes for pro-opiomelanocortin, the precursor for hormones of the melanocortin system. Several genes putatively involved in downstream processing of pro-opiomelanocortin were manually annotated, and were found to be highly expressed, both by RNA-seq and by qPCR. The melanocortin system, which affects skin color, energy homeostasis and in other teleosts interacts with the reproductive system, has so far received limited attention in eels. However, since up to one third of the silver eel pituitary's mRNA pool encodes pro-opiomelanocortin, our results indicate that control of the melanocortin system is a major function of the eel pituitary.