The Role of Lifestyle and Dietary Factors in the Development of Premature Ovarian Insufficiency

Abstract

Premature ovarian insufficiency (POI) is a condition that arises from dysfunction or early depletion of the ovarian follicle pool accompanied by an earlier-than-normal loss of fertility in young women. Oxidative stress has been suggested as an important factor in the decline of fertility in women and POI. In this review, we discuss the mechanisms of oxidative stress implicated in ovarian ageing and dysfunction in relation to POI, in particular mitochondrial dysfunction, apoptosis and inflammation. Genetic defects, autoimmunity and chemotherapy, are some of the reviewed hallmarks of POI that can lead to increased oxidative stress. Additionally, we highlight lifestyle factors, including diet, low energy availability and BMI, that can increase the risk of POI. The final section of this review discusses dietary factors associated with POI, including consumption of oily fish, mitochondria nutrient therapy, melatonin, dairy and vitamins that can be targeted as potential interventions, especially for at-risk women and in combination with personalised nutrition. Understanding the impact of lifestyle and its implications for POI and oxidative stress holds great promise in reducing the burden of this condition.

A Literature Review and a Proposed Classification of the Relationships between Ovulatory Infertility and Lifestyle Factors Based on the Three Groups of Ovulation Disorders Classified by WHO

“…This is why it would be worthwhile to conduct studies focused on specific oxidative stress triggers, which could narrow down the topic and lead to results that would be clinically applicable. OS has also been studied in the context of WHO Group III ovulation disorders, i.e., primary ovarian insufficiency, with a causative link proposed by the researchers [37]. This tentative finding, based on a relatively new idea, could be examined further, provided that a robust clinical study could be designed.…”

“…Thus, primary ovarian insufficiency is often thought as unrelated to lifestyle or adherence to a proper diet [36]. Studies exist, however, that suggest otherwise, i.e., that the condition could be delayed or better managed through personalized dietary and lifestyle recommendations based on genetics, with the rationale for such conclusions rooted in the possible influence of oxidative stress and inflammation postulated by the researchers [37]. Such conclusions, nevertheless, seem far-fetched and would be difficult to prove experimentally, with the study admitting that genetic causes indeed play the most important role in the development of primary ovarian insufficiency.…”

“…It should also be mentioned that a causative connection has been suggested between increased levels of oxidative stress and primary ovarian insufficiency [37], a WHO Group III disorder. However, the study is of a very speculative character and involves a large number of confounded variables, which is why to be considered clinically relevant, its conclusions would need a corroboration in the form of a sound experimental study.…”

Protective role of stem cells in POI: Current status and mechanism of action, a review article

“…The impaired protective role of estrogen and progesterone against apoptosis in POI patients can justify this abnormality [ 44 ]. Oxidative stress is considered as an important contributing factor in triggering ovarian apoptosis [ 45 ]. Excess ROS can induce apoptosis through mitochondrial dysfunction, recruitment of a series of caspase cascades, pro-inflammatory cytokine activation and via increasing phosphorylation of c-Jun N-terminal kinases (JNKs) and P53 pathways [ 46 ].…”

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions

“… Potential mechanisms of ovarian aging (the figure was created with ) Telomere shortening: Once telomere length becomes critically short, cellular senescence and apoptosis may occur during ovarian aging in mammals ( 7 , 8 ); Compromised autophagy: The decrease of autophagic activity with age, likely leads to the accumulation of damaged macromolecules and organelles ( 9 , 10 ); Mitochondial dysfunction: Mitochondial factors are explained further under subheadings in the text; Loss of proteostasis: Loss of proteostasis may damage the stability of microtubules and the integrity of meiosis in naturally aged mice oocyte ( 11 ); Stem cell exhaustion: Due to germ-line stem cells do not exist post-natally in female mammals ( 12 – 14 ), the reproductive potential of the ovaries will continue to decline after birth; Altered intercellular communication: There is an Increase In preantral follicles atresia in mice with suppression of intercellular junctions, which may be the cause of premature ovarian failure ( 15 , 16 ); Epigenetic alteration: Studies have revealed the occurrence of epigenetic changes in the cells within the ovaries as age increases, including abnormal DNA methylation ( 17 ), histone modifications ( 18 ), and non-coding RNA-regulated modifications ( 19 , 20 ); Cellular senescence: With the dysfunction of senescent cell, limited mitochondrial energy production, increased apoptosis of ovarian granulosa cells ( 21 ), increased inflammatory cytokines secretion ( 22 ) etc., would alter the microenvironment of follicle growth and affecting the quality and quantity of oocyte; Nutritional dysregulation: Dietary factors ( 23 ), low energy availability and high fat diet can increase the risk of POI; Genomic instability: In aging oocyte deceased efficacy of DNA repair mechanisms could cause low potentiation of anti-oxidant buffering and promote cell death ( 24 ). …”