madman
Super Moderator
Abstract
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20–25% of women of reproductive age. Different mechanisms could contribute to the development of its typical clinical features (i.e. hirsutism, acne, oligo-amenorrhea, alopecia). Some genetic and epigenetic aspects and lifestyle changes seem to be involved in PCOS development. In this review, we shall summarize data from principal studies evaluating the impact of major genetic, epigenetic, and environmental factors on the appearance of this female disorder. Literature review and analysis of the most relevant data until May 2020. Current data suggest the importance of genetics and epigenetics in the appearance of PCOS. Several genes, including those related to adrenal and ovarian steroidogenesis as well as those associated with hormonal response to gonadotrophins, androgens, and insulin, have been demonstrated to be associated with PCOS. Besides, the phenomenon of methylation of genes and the presence of specific microRNA (miRNA) could take part in PCOS etiology. Intrauterine exposure to androgens, glucocorticoids, and/or some stressful conditions for fetuses could contribute to the development of PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis, and Advanced Glycation End-products (AGEs) in PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis, and Advanced Glycation End-products (AGEs) in PCOS. PCOS is a polygenic and multifactorial hormonal and metabolic dysfunction. Appropriate knowledge of the personal and/or family history, lifestyle, and nutritional habits of PCOS patients has great importance to early identify and manage this syndrome.
Introduction
Polycystic ovary syndrome (PCOS) is a hormonal and metabolic disorder characterized by menstrual irregularities, hyperandrogenism (acne, amenorrhea, alopecia, etc.) and, sometimes, infertility [1, 2]. It is well recognized [3] that several hormonal alterations can favor the clinical appearance of PCOS: for example, the increased serum levels of male hormones, like testosterone (T) and/or androstenedione (A), that is to say hyperandrogenemia could produce skin signs like hirsutism and/or acne and alter lipid profile [3]. At the same time, the decreased insulin sensitivity associated with compensatory hyperinsulinemia may negatively influence glycaemic homeostasis and affect per se ovarian function [4, 5].
It must be underlined that the variable expressiveness of PCOS may partially depend on the biological characteristics of each affected woman as well as on her lifestyle context and/ or genetic predisposition [6]. Many authors pointed out the key role of environment, intrauterine, and infancy history in the development of PCOS [7]. However, the actual involvement of genetic, epigenetic, and environmental factors in this syndrome is still a matter of debate.
In this paper, we shall review the most important data about the relationship between PCOS and genetics, epigenetics and lifestyle. Our main purpose is to provide an updated narrative review of several interesting features of PCOS, other than hormonal and metabolic changes. Hereby, clinicians could approach and manage this complex syndrome with higher awareness, taking into account the importance of family history, intrauterine life, and personal behavior in the appearance of PCOS.
*Ethnicity
*Heritability
*Genetics
*Epigenetics and Intrauterine Environment
*Extrauterine Environment
Conclusions
PCOS is a very challenging endocrine-metabolic disorder since various aspects need to be considered to frame and manage its clinical features, as in the case of other multifactorial diseases. This is an updated narrative review discussing the most recent evidence about the role of genetics, epigenetics, and environment in the development and maintenance of this syndrome in young adult life.
According to the available data, both heritability and genetics can have an important role in the appearance of PCOS [11, 12, 19]. In fact, on the one hand, a familiar trait of susceptibility to hyperandrogenism can be found among affected subjects, particularly among some female first-degree relatives of PCOS women, even if in absence of a clear and complete clinical evidence of the syndrome according to the classical diagnostic criteria [16]. On the other hand, different genes, such as those associated with adrenal and ovarian steroidogenesis, ARs, gonadotrophin, and insulin activity, and inflammatory response, were proposed to be involved in the etiology of this syndrome [18–55]. Nevertheless, robust evidence demonstrating the predominance of a specific gene for PCOS is still lacking
Many epigenetic modifications (e.g. the methylation of specific genes and/or the presence of miRNAs) [57, 64–70] seem to influence the phenotype of PCOS patients. Furthermore, medical history of mothers before and during pregnancy (e.g. a previous diagnosis of PCOS, hyperinsulinemia, diabetes, preeclampsia) and/or some intrauterine events inducing a “fetal distress”, could affect the reproductive health of female fetuses during adolescence and adult life [80–82].
As for exogenous factors, although the role of dysbiosis of gut microbiome, endocrine disruptors, and AGEs in the development of PCOS needs further elucidations [97, 102, 103, 105], a healthy lifestyle associated with a well-balanced, poor of saturated fatty acids and rich of grains diet associated with a medical tailored treatment could sustain the metabolic and hormonal management of PCOS women [109].
Taken together all these findings, clinicians should manage signs and symptoms of PCOS and prevent its possible long-term consequences more consciously (Fig. 1).
An aware knowledge of all the mechanisms at the basis of PCOS development could favor the promotion, achievement and maintenance of well-being in all affected subjects.
Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease affecting about 20–25% of women of reproductive age. Different mechanisms could contribute to the development of its typical clinical features (i.e. hirsutism, acne, oligo-amenorrhea, alopecia). Some genetic and epigenetic aspects and lifestyle changes seem to be involved in PCOS development. In this review, we shall summarize data from principal studies evaluating the impact of major genetic, epigenetic, and environmental factors on the appearance of this female disorder. Literature review and analysis of the most relevant data until May 2020. Current data suggest the importance of genetics and epigenetics in the appearance of PCOS. Several genes, including those related to adrenal and ovarian steroidogenesis as well as those associated with hormonal response to gonadotrophins, androgens, and insulin, have been demonstrated to be associated with PCOS. Besides, the phenomenon of methylation of genes and the presence of specific microRNA (miRNA) could take part in PCOS etiology. Intrauterine exposure to androgens, glucocorticoids, and/or some stressful conditions for fetuses could contribute to the development of PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis, and Advanced Glycation End-products (AGEs) in PCOS and other disorders observed in adolescence and later (e.g. premature adrenarche, atypical puberty, metabolic syndrome). Emerging studies report a theoretical role of endocrine disruptors, intestinal dysbiosis, and Advanced Glycation End-products (AGEs) in PCOS. PCOS is a polygenic and multifactorial hormonal and metabolic dysfunction. Appropriate knowledge of the personal and/or family history, lifestyle, and nutritional habits of PCOS patients has great importance to early identify and manage this syndrome.
Introduction
Polycystic ovary syndrome (PCOS) is a hormonal and metabolic disorder characterized by menstrual irregularities, hyperandrogenism (acne, amenorrhea, alopecia, etc.) and, sometimes, infertility [1, 2]. It is well recognized [3] that several hormonal alterations can favor the clinical appearance of PCOS: for example, the increased serum levels of male hormones, like testosterone (T) and/or androstenedione (A), that is to say hyperandrogenemia could produce skin signs like hirsutism and/or acne and alter lipid profile [3]. At the same time, the decreased insulin sensitivity associated with compensatory hyperinsulinemia may negatively influence glycaemic homeostasis and affect per se ovarian function [4, 5].
It must be underlined that the variable expressiveness of PCOS may partially depend on the biological characteristics of each affected woman as well as on her lifestyle context and/ or genetic predisposition [6]. Many authors pointed out the key role of environment, intrauterine, and infancy history in the development of PCOS [7]. However, the actual involvement of genetic, epigenetic, and environmental factors in this syndrome is still a matter of debate.
In this paper, we shall review the most important data about the relationship between PCOS and genetics, epigenetics and lifestyle. Our main purpose is to provide an updated narrative review of several interesting features of PCOS, other than hormonal and metabolic changes. Hereby, clinicians could approach and manage this complex syndrome with higher awareness, taking into account the importance of family history, intrauterine life, and personal behavior in the appearance of PCOS.
*Ethnicity
*Heritability
*Genetics
*Epigenetics and Intrauterine Environment
*Extrauterine Environment
Conclusions
PCOS is a very challenging endocrine-metabolic disorder since various aspects need to be considered to frame and manage its clinical features, as in the case of other multifactorial diseases. This is an updated narrative review discussing the most recent evidence about the role of genetics, epigenetics, and environment in the development and maintenance of this syndrome in young adult life.
According to the available data, both heritability and genetics can have an important role in the appearance of PCOS [11, 12, 19]. In fact, on the one hand, a familiar trait of susceptibility to hyperandrogenism can be found among affected subjects, particularly among some female first-degree relatives of PCOS women, even if in absence of a clear and complete clinical evidence of the syndrome according to the classical diagnostic criteria [16]. On the other hand, different genes, such as those associated with adrenal and ovarian steroidogenesis, ARs, gonadotrophin, and insulin activity, and inflammatory response, were proposed to be involved in the etiology of this syndrome [18–55]. Nevertheless, robust evidence demonstrating the predominance of a specific gene for PCOS is still lacking
Many epigenetic modifications (e.g. the methylation of specific genes and/or the presence of miRNAs) [57, 64–70] seem to influence the phenotype of PCOS patients. Furthermore, medical history of mothers before and during pregnancy (e.g. a previous diagnosis of PCOS, hyperinsulinemia, diabetes, preeclampsia) and/or some intrauterine events inducing a “fetal distress”, could affect the reproductive health of female fetuses during adolescence and adult life [80–82].
As for exogenous factors, although the role of dysbiosis of gut microbiome, endocrine disruptors, and AGEs in the development of PCOS needs further elucidations [97, 102, 103, 105], a healthy lifestyle associated with a well-balanced, poor of saturated fatty acids and rich of grains diet associated with a medical tailored treatment could sustain the metabolic and hormonal management of PCOS women [109].
Taken together all these findings, clinicians should manage signs and symptoms of PCOS and prevent its possible long-term consequences more consciously (Fig. 1).
An aware knowledge of all the mechanisms at the basis of PCOS development could favor the promotion, achievement and maintenance of well-being in all affected subjects.
