Department of Biological Sciences, Birla Institute of Technology and Science, K K Birla Goa Campus, Zuarinagar, Goa, India.
Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, 333031, India.
Theriogenology. 2024 Nov;229:202-213. doi: 10.1016/j.theriogenology.2024.07.028. Epub 2024 Aug 31.
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.
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.
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.
下丘脑-垂体-性腺（HPG）轴在调节生殖功能方面起着至关重要的作用，促性腺激素释放激素（GnRH）作为中央调节剂。最近，多胺已被证明可以调节 HPG 轴，包括在老年和成年啮齿动物中 GnRH 的表达和卵巢生物学。本研究首先强调了在衰老过程中，卵巢中多胺及其相应生物合成酶的年龄特异性变化，并且进一步研究了多胺、腐胺和胍丁胺对年轻雌性小鼠的影响。
免疫荧光分析显示，卵巢中鸟氨酸脱羧酶 1（ODC1）、精胺（SPM）和精脒（SPD）的表达存在与年龄相关的差异，成年小鼠的表达水平明显高于年轻和老年小鼠。同样，qPCR 分析显示 Odc1、精脒合酶（Srm）和精胺合酶（Sms）的 mRNA 水平在成年卵巢中显著增加，然后在老年时显著下降。组织学检查显示，随着年龄的增长，卵巢发生形态改变，老年小鼠的卵泡数量减少，间质细胞增多。此外，与对照组相比，年轻小鼠用多胺腐胺处理后，卵巢增大，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）和孕激素（P4）的水平，发现多胺处理小鼠的水平升高。GnRH mRNA 表达也显著增加。基因表达分析显示，卵巢中与卵泡发生相关的基因如 Fshr、Bmp15、Gdf9、Amh、Star、Hsdb3 和 Plaur 以及下丘脑中小鼠促性腺激素释放激素的基因如 Tac2 和 Kiss1 的表达上调，多胺处理小鼠的 Mkrn3 表达下调。
本研究探讨了多胺对年轻未成熟雌性小鼠的影响，揭示了它们在上调 GnRH 和增强卵泡发生中的作用。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，为恢复生殖挑战个体的生育能力提供了潜在的治疗方法。
