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Review
. 2023 Oct 18;24(20):15330.
doi: 10.3390/ijms242015330.

Polyamines in Ovarian Aging and Disease

Bo Kang  1   2 , Xin Wang  1   2 , Xiaoguang An  1   2 , Chengweng Ji  1   2 , Weikang Ling  1   2 , Yuxin Qi  1   2 , Shuo Li  1   2 , Dongmei Jiang  1   2
Affiliations
Review

Polyamines in Ovarian Aging and Disease

Bo Kang et al. Int J Mol Sci. .

Abstract

Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases.

Keywords: aging; autophagy; cancer; disease; ovary; polyamine.

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Conflict of interest statement

The authors declared no conflict of interest.

Figures

Figure 1
Figure 1
Schematic figure of the core polyamine metabolic pathway in eukaryotes. Met: methionine. MAT: S-adenosylmethionine synthase. SAM: S-adenosylmethionine. SAMDC: S-adenosylmethionine decarboxylase. dcSAM: decarboxylated S-adenosylmethionine. SPDS: spermidine synthase. SPMS: spermine synthase. SMO: spermine oxidase. OAZ: ornithine decarboxylase antizyme. ODC: ornithine decarboxylase. APAO: acetylpolyamine oxidase. AcSpd: acetylspermidine. SSAT: spermidine/spermine N1-acetyltransferase. AcSpm: acetylspermine.
Figure 2
Figure 2
Spermidine mediates eIF5A hypusination to promote autophagy. DHPS: deoxyhypusine synthase. DOHH: deoxyhypusine hydroxylase.
Figure 3
Figure 3
Polyamines prevent ovarian aging. Ovarian aging is associated with oxidative stress, apoptosis, inflammation, mitochondrial dysfunction, telomere loss, and autophagy, which are functionally correlated with each other. Spermidine may alleviate ovarian aging through various mechanisms, such as promoting autophagy, attenuating oxidative stress and inflammation, enhancing mitochondrial biogenesis, and preventing telomere shortening. AMPK: adenosine 5′-monophosphate (AMP)-activated protein kinase. mTOR: mammalian target of rapamycin. ULK1: human autophagy initiation protein 1. KITKG: KIT ligand. CAT: catalase. GPX4: recombinant glutathione peroxidase 4. GSH: L-glutathione. HO-1: heme oxygenase.
Figure 4
Figure 4
Polyamine metabolism regulates the development of ovarian cancer. (Left) Inhibition of ODC, a key target of anabolic enzymes in polyamine metabolism, can hinder the development of ovarian cancer. (Middle) In normal cells, spermidine may regulate the translation of some autophagy-related genes by mediating hyp-eIF5A, thereby inhibiting the development of ovarian cancer. Spermidine may promote the development of ovarian cancer by regulating oncogene translation through hyp-eIF5A. (Right) Anticancer drugs inhibit the development of ovarian cancer by targeting the catabolic enzymes of polyamine metabolism, such as SSAT and SMO.
See this image and copyright information in PMC

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