背景:下丘脑-垂体-性腺(HPG)轴在调节生殖功能方面至关重要,以促性腺激素释放激素(GnRH)作为中枢调节剂。最近,多胺已被证明可以调节HPG轴,包括老年和成年啮齿动物的GnRH表达和卵巢生物学。本研究首先强调了衰老过程中卵巢多胺及其相应生物合成酶的年龄特异性变化,进一步,这项研究的重点是多胺的作用,腐胺,和胍丁胺,年轻的雌性老鼠。
结果:免疫荧光分析显示鸟氨酸脱羧酶1(ODC1)表达的年龄相关差异,精胺(SPM),和卵巢中的亚精胺(SPD),与年轻和老年小鼠相比,成年小鼠表现出明显更高的表达水平。同样,qPCR分析显示Odc1,亚精胺合酶(Srm)的mRNA水平,精胺合成酶(Sms)在成年卵巢中显示出显着的增加,然后是老年显着下降。组织学检查显示卵巢随着年龄的增加而发生形态学改变,包括老年小鼠卵泡数量减少和基质细胞增加。此外,用腐胺治疗,一种多胺,与对照组相比,年轻小鼠的卵巢更大,卵泡数量增加。此外,测定血清促性腺激素释放激素(GnRH)和孕酮(P4)水平,在多胺处理的小鼠中显示水平升高。GnRHmRNA表达也显著增加。基因表达分析显示与卵泡发生相关的基因上调,如Fshr,Bmp15,Gdf9,Amh,明星,卵巢中的Hsdb3和Plaur以及青春期的开始,例如Tac2和Kiss1,以及多胺处理的小鼠下丘脑中Mkrn3的降低。
结论:这项研究调查了多胺对幼年未成熟雌性小鼠的影响,阐明它们在上调GnRH中的作用,增强卵泡生成。总的来说,这些发现表明,多胺在卵巢衰老和HPG轴调节中起着至关重要的作用,提供潜在的治疗方法来恢复生殖挑战个体的生育能力。
BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice.
RESULTS: Immunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice.
CONCLUSIONS: This study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals.