The Molecular Regulation in the Pathophysiology in Ovarian Aging

Li, Chia-Jung; Lin, Lie Chwen; Tsai, Hsiao Wen; Chern, Chyi-Uei; Wen, Zhi‐Hong; Wang, Peng-Hui; Tsui, Kuan‐Hao

doi:10.14336/ad.2020.1113

Cited by 35 publications

(36 citation statements)

References 165 publications

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“…4) Diabetes is known to be associated with an accelerated rate of the accumulation of advanced glycation end products (AGEs) ( 55 ). The accumulation of AGEs has been reported to be closely related to declining ovarian function ( 56 ). The glycation process causes protein damage, and the interaction of AGEs and their receptors could lead to the activation of a number of proinflammatory pathways, increased production of ROS in oocytes, and endothelial dysfunction via inactivation of endothelial nitric oxide synthase and prostacyclin synthase, thereby inducing a premature decline in ovarian function ( 48 , 56 ).…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of AGEs has been reported to be closely related to declining ovarian function ( 56 ). The glycation process causes protein damage, and the interaction of AGEs and their receptors could lead to the activation of a number of proinflammatory pathways, increased production of ROS in oocytes, and endothelial dysfunction via inactivation of endothelial nitric oxide synthase and prostacyclin synthase, thereby inducing a premature decline in ovarian function ( 48 , 56 ). Moreover, AGEs were reported to accelerate the progression of nuclear maturation, though the mechanisms still unknown ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

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Accelerated Ovarian Aging Among Type 2 Diabetes Patients and Its Association With Adverse Lipid Profile

Wang

2022

Front. Endocrinol.

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BackgroundThe impact of diabetes on reproductive function is still not clearly defined. This study aimed to evaluate accelerated ovarian aging in women with type 2 diabetes mellitus (T2DM) and its association with adverse lipid profile.MethodsFemale patients with T2DM (n=964) and non-T2DM controls (n=263) aging from 18-80 years were included. Levels of circulating sex hormones were measured at the follicular phase in menstruating women. We analyzed the age-specific trends in the levels of sex hormones between T2DM and controls. The correlations of sex hormones with the lipid profile, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG) were also evaluated.ResultsIn the temporal trends analysis, LH and FSH both started to increase obviously approximately from the age of 45 years among patients with T2DM, and displayed peaks of LH and FSH among patients with T2DM aged between 61 and 65, both of which were obviously earlier than that in non-T2DM controls and proved the accelerated ovarian aging among patients with T2DM. E2 of patients with T2DM was continuous lower than that of non-T2DM controls from approximately 45 years old, and LH and FSH of patients with T2DM were higher than those of non-T2DM controls between the age of 55 to 65 years. Multiple linear regression analyses revealed that LH was positively correlated with LDL-C (Coefficient=0.156, P=0.001) and TC (Coefficient=0.134, P=0.025), and was negatively correlated with HDL-C (Coefficient =-0.065, P=0.001) in patients with T2DM aged between 51 and 60, which was independent of age, T2DM duration, body mass index (BMI), glycosylated hemoglobin (HbA1c), FSH, E2 and other potential confounders. Higher E2 level was significantly and independently correlated with lower LDL-C (Coefficient= -0.064, P=0.033) in patients with T2DM aged between 51 and 60.ConclusionsThis study suggests that patients with T2DM have accelerated ovarian aging, and it is correlated with the occurrence of disturbed lipid profile in patients with T2DM. With an ever increasing number of female patients with T2DM diagnosed at younger ages, the accelerated ovarian aging and its adverse impacts in T2DM need to be carefully managed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accelerated Ovarian Aging Among Type 2 Diabetes Patients and Its Association With Adverse Lipid Profile

Wang

2022

Front. Endocrinol.

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“…Although medical care advances and rising living standards have contributed to increasing lifespan, the age of menopause has remained constant at the age of ~50 years, leading women to live longer in suboptimal endocrine conditions [ 4 ]. Reproductive aging has therefore gradually become a key health issue and an adequate understanding of its mechanisms is essential in order to prevent age-related diseases and to promote health and longevity in women [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Aging on the Ovarian Extracellular Matrix and Derived 3D Scaffolds

et al. 2022

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Advances in medical care, improvements in sanitation, and rising living standards contribute to increased life expectancy. Although this reflects positive human development, it also poses new challenges. Among these, reproductive aging is gradually becoming a key health issue because the age of menopause has remained constant at ~50 years, leading women to live longer in suboptimal endocrine conditions. An adequate understanding of ovarian senescence mechanisms is essential to prevent age-related diseases and to promote wellbeing, health, and longevity in women. We here analyze the impact of aging on the ovarian extracellular matrix (ECM), and we demonstrate significant changes in its composition and organization with collagen, glycosaminoglycans, and laminins significantly incremented, and elastin, as well as fibronectin, decreased. This is accompanied by a dynamic response in gene expression levels of the main ECM- and protease-related genes, indicating a direct impact of aging on the transcription machinery. Furthermore, in order to study the mechanisms driving aging and identify possible strategies to counteract ovarian tissue degeneration, we here described the successful production of a 3D ECM-based biological scaffold that preserves the structural modifications taking place in vivo and that represents a powerful high predictive in vitro model for reproductive aging and its prevention.

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“…The mitochondria of germ cells require extremely high energy to maintain cell physiology and a large number of mitochondrial dynamics to maintain homeostasis (Li et al, 2021 ). Mitochondria are highly dynamic organelles that can continuously move, fuse, and divide according to changes in the cellular energy requirements.…”

Section: Introductionmentioning

confidence: 99%

Phosphoglycerate mutase family member 5 maintains oocyte quality via mitochondrial dynamic rearrangement during aging

Lin

Tsai

et al. 2022

Aging Cell

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Decline in ovarian reserve with aging is associated with reduced fertility and the development of metabolic abnormalities. Once mitochondrial homeostasis is imbalanced, it may lead to poor reproductive cell quality and aging. However, Phosphoglycerate translocase 5 (PGAM5), located in the mitochondrial membrane, is associated with necroptosis, apoptosis, and mitophagy, although the underlying mechanisms associated with ovarian aging remain unknown. Therefore, we attempted to uncover whether the high phosphoglycerate mutant enzyme family member 5 (PGAM5) expression is associated with female infertility in cumulus cells, and aims to find out the underlying mechanism of action of PGAM5. We found that PGAM5 is highly expressed and positively associated with aging, and has the potential to help maintain and regulate mitochondrial dynamics and metabolic reprogramming in aging granulosa cells, ovaries of aged female mice, and elderly patients. PGAM5 undergoes activation in the aging group and translocated to the outer membrane of mitochondria, co‐regulating DRP1; thereby increasing mitochondrial fission. A significant reduction in the quality of mitochondria in the aging group, a serious imbalance, and a significant reduction in energy, causing metabolism shift toward glycolysis, were also reported. Since PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed. A total of 70 patients undergoing in vitro fertilization (IVF) treatment were recruited in this clinical study. The high expression of PGAM5 in the cumulus cells is negatively correlated with the pregnancy rate of infertile patients. Hence, PGAM5 has immense potential to be used as a diagnostic marker.

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The Molecular Regulation in the Pathophysiology in Ovarian Aging

Cited by 35 publications

References 165 publications

Accelerated Ovarian Aging Among Type 2 Diabetes Patients and Its Association With Adverse Lipid Profile

Accelerated Ovarian Aging Among Type 2 Diabetes Patients and Its Association With Adverse Lipid Profile

Impact of Aging on the Ovarian Extracellular Matrix and Derived 3D Scaffolds

Phosphoglycerate mutase family member 5 maintains oocyte quality via mitochondrial dynamic rearrangement during aging

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