Reduced Circulating Polyamines in Polyendocrine Metabolic Ovarian Syndrome (PMOS) Patients and the Impact of Putrescine on Ovarian Function and Fertility in a Murine PMOS Model

Abstract

GnRH is essential for regulating the reproductive system in mammals. Recent research has shown that polyamines, biogenic amines produced in body, can regulate GnRH levels. These polyamine levels are affected by metabolic disorders like diabetes and obesity. However, it remains unclear whether changes in polyamine expression are related to PMOS, which is characterised by altered GnRH patterns. Circulatory polyamine levels were measured in PMOS patients. In a study on prepubertal female Balb/c mice induced with a PMOS-like condition using DHEA, the mice were treated with polyamines (putrescine, agmatine, and DFMO) for 5 days. The effects on body weight, serum glucose, testosterone, GnRH, GnIH levels, and gene expression related to ovarian inflammation and folliculogenesis were observed. The study found that circulatory polyamines (putrescine, spermidine, spermine) are lower in PMOS patients than in healthy individuals. A single dose of putrescine improved PMOS-like symptoms in mice by reducing GnRH, glucose, testosterone levels, body weight, and inflammation in the ovary. Exogenous polyamine treatment increased endogenous polyamine markers in the hypothalamus and ovary, thereby improving fertility and pregnancy outcomes in PMOS mice by regulating key uterine markers. These findings suggest that circulating polyamine levels vary between PMOS and healthy individuals. Exogenous polyamine treatment enhances GnRH metabolism in the hypothalamus by modulating endogenous polyamine genes, thereby improving PMOS traits and ovarian morphology, reducing serum testosterone levels, and supporting successful pregnancy. The authors thereby suggest that endogenous polyamines are key to the pathophysiology of PMOS, and that exogenous polyamines could be a potential target for PMOS management.