Impact of polyamine supplementation on GnRH expression, folliculogenesis, and puberty onset in young mice

IF 2.4 2区 农林科学 Q3 REPRODUCTIVE BIOLOGY
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Abstract

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.

Method and result

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.

Conclusion

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.

Abstract Image

补充多胺对幼鼠 GnRH 表达、卵泡生成和青春期开始的影响
背景下丘脑-垂体-性腺轴(HPG)在调节生殖功能方面起着关键作用,其中促性腺激素释放激素(GnRH)起着核心调节作用。最近,多胺被证明可以调节 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中多胺及其相应生物合成酶的年龄特异性变化,然后重点研究了多胺、腐胺和矢车菊碱对年轻雌性小鼠的影响。方法和结果免疫荧光分析显示,卵巢中鸟氨酸脱羧酶 1(ODC1)、精胺(SPM)和亚精胺(SPD)的表达与年龄有关,成年小鼠的表达水平明显高于年轻小鼠和老年小鼠。同样,qPCR 分析表明,成年小鼠卵巢中的 Odc1、精胺合成酶(Srm)和精胺合成酶(Sms)的 mRNA 水平显著升高,到老年时则显著下降。组织学检查显示,随着年龄的增长,卵巢的形态也会发生变化,包括老年小鼠卵泡数量减少,基质细胞增加。此外,与对照组相比,用多胺--腐胺处理年轻小鼠会使卵巢变大,卵泡数量增加。此外,还测量了血清中促性腺激素释放激素(GnRH)和孕酮(P4)的水平,结果显示多胺处理的小鼠血清中促性腺激素释放激素(GnRH)和孕酮(P4)的水平升高。GnRH mRNA 的表达也显著增加。基因表达分析表明,多胺处理小鼠卵巢中与卵泡生成相关的基因(如 Fshr、Bmp15、Gdf9、Amh、Star、Hsdb3 和 Plaur)和青春期开始相关的基因(如 Tac2 和 Kiss1)上调,而下丘脑中的 Mkrn3 则下降。结论 本研究调查了多胺对未成熟幼年雌性小鼠的影响,揭示了多胺在上调 GnRH 和促进卵泡生成方面的作用。总之,这些研究结果表明,多胺在卵巢衰老和 HPG 轴调节中起着至关重要的作用,为恢复生殖障碍个体的生育能力提供了潜在的治疗方法。
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来源期刊
Theriogenology
Theriogenology 农林科学-生殖生物学
CiteScore
5.50
自引率
14.30%
发文量
387
审稿时长
72 days
期刊介绍: Theriogenology provides an international forum for researchers, clinicians, and industry professionals in animal reproductive biology. This acclaimed journal publishes articles on a wide range of topics in reproductive and developmental biology, of domestic mammal, avian, and aquatic species as well as wild species which are the object of veterinary care in research or conservation programs.
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