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<p>Polycystic Ovary Syndrome (PCOS) is a prevalent, multifaceted endocrine disorder marked by impaired lipid metabolism and insulin resistance, contributing to hormonal imbalance. The hydroxy acid oxidase 2 (HAO2) gene plays a key role in fatty acid degradation pathways, and its altered expression may influence metabolic and endocrine dysfunctions associated with PCOS. Our study, therefore, for the first time, aimed to investigate the expression pattern of HAO2 during various phases of the estrous cycle and evaluate its role in the modulation of gonadal hormones in the context of PCOS. Additionally, we examined HAO2 expression in the ovaries of a letrozole-induced PCOS mouse model and explored its correlation with circulating steroid hormones and lipid metabolic genes. Strong immunoreactivity for HAO2 in luteal cells of all the phases of estrous cycle and increased expression in the proestrus phase suggest that an intricate balance of HAO2 activity is required for both luteinization and luteolysis processes. In PCOS ovaries, HAO2 protein levels were markedly reduced compared to vehicle controls. Notably, reduced HAO2 expression showed a negative correlation with circulating progesterone and testosterone levels, while a positive correlation with estradiol, emphasising its involvement in hyperandrogenism-linked ailment. Additionally, mRNA expression of lipid metabolism genes showing a strong negative correlation with HAO2 indicates its possible involvement in PCOS pathogenesis. Collectively, our data imply that HAO2 may play a significant role in PCOS by modulating lipid metabolism, thereby alleviating hyperandrogenic pathophysiology.</p>

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Hydroxy acid oxidase 2 expression in mouse ovary during estrous cycle and its alteration in letrozole-induced polycystic ovary syndrome

  • 期刊论文

  • 发表日期：

    2026年7月21日

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  • Rakhi Rakhi,
  • Mahak Gupta,
  • Ajit Singh

摘要

Polycystic Ovary Syndrome (PCOS) is a prevalent, multifaceted endocrine disorder marked by impaired lipid metabolism and insulin resistance, contributing to hormonal imbalance. The hydroxy acid oxidase 2 (HAO2) gene plays a key role in fatty acid degradation pathways, and its altered expression may influence metabolic and endocrine dysfunctions associated with PCOS. Our study, therefore, for the first time, aimed to investigate the expression pattern of HAO2 during various phases of the estrous cycle and evaluate its role in the modulation of gonadal hormones in the context of PCOS. Additionally, we examined HAO2 expression in the ovaries of a letrozole-induced PCOS mouse model and explored its correlation with circulating steroid hormones and lipid metabolic genes. Strong immunoreactivity for HAO2 in luteal cells of all the phases of estrous cycle and increased expression in the proestrus phase suggest that an intricate balance of HAO2 activity is required for both luteinization and luteolysis processes. In PCOS ovaries, HAO2 protein levels were markedly reduced compared to vehicle controls. Notably, reduced HAO2 expression showed a negative correlation with circulating progesterone and testosterone levels, while a positive correlation with estradiol, emphasising its involvement in hyperandrogenism-linked ailment. Additionally, mRNA expression of lipid metabolism genes showing a strong negative correlation with HAO2 indicates its possible involvement in PCOS pathogenesis. Collectively, our data imply that HAO2 may play a significant role in PCOS by modulating lipid metabolism, thereby alleviating hyperandrogenic pathophysiology.