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The genetics of premature ovarian failure: current perspectives.

Chapman C, Cree L, Shelling AN - Int J Womens Health (2015)

Bottom Line: The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF.Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF.The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

ABSTRACT
Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been identified that can explain a substantial proportion of cases of POF. The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF. As only a small proportion of genes influencing idiopathic POF have been identified thus far, it remains to be determined how many genes and molecular pathways may influence idiopathic POF development. However, owing to POF's diverse etiology and genetic heterogeneity, we expect to see the contribution of several new and novel molecular pathways that will greatly enhance our understanding of the regulation of ovarian function. Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF. The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.

No MeSH data available.


Related in: MedlinePlus

A schematic representation of the process of folliculogenesis in the mammalian ovary from primordial follicles through to follicle ovulation and subsequent corpus luteum formation.Notes: Initial recruitment is gonadotropin independent and involves the differentiation of primordial follicles into primary and preantral follicles, the majority of which undergo atresia prior to puberty. Cyclic recruitment occurs after puberty and is gonadotropin dependent. Cyclic recruitment involves the growth and development of antral follicles through to mature preovulatory follicle selection and ovulation or atresia. This process continues throughout a female’s reproductive lifespan until the primordial follicle pool is depleted.
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f1-ijwh-7-799: A schematic representation of the process of folliculogenesis in the mammalian ovary from primordial follicles through to follicle ovulation and subsequent corpus luteum formation.Notes: Initial recruitment is gonadotropin independent and involves the differentiation of primordial follicles into primary and preantral follicles, the majority of which undergo atresia prior to puberty. Cyclic recruitment occurs after puberty and is gonadotropin dependent. Cyclic recruitment involves the growth and development of antral follicles through to mature preovulatory follicle selection and ovulation or atresia. This process continues throughout a female’s reproductive lifespan until the primordial follicle pool is depleted.

Mentions: The end of a woman’s reproductive lifespan is marked by the occurrence of menopause, defined as being the last menstruation that occurs for a woman, but is caused by the exhaustion of the ovarian reserve.1 In the general female population, across many ethnicities and over recent human history, the average age of natural menopause has remained at 50–52 years. However, aberrations in ovulatory processes, as outlined in Figure 1, may cause a pathogenic early depletion of ovarian follicles, which may result in premature menopause. Menopause before the age of 40 years is defined as premature ovarian failure (POF), also known as primary ovarian insufficiency.2 POF is described as the premature cessation of ovarian function and is characterized by 4–6 months of amenorrhea, a rise in serum follicle-stimulating hormone (FSH) levels to greater than 40 mIU/L, and hypoestrogenism.2,3 POF is a common disease, occurring in 1% of all women and 0.1% of women below the age of 30 years.2 As a consequence of hypoestrogenism, POF is associated with a greater risk of osteoporosis, osteoarthritis, and cardiovascular disease.4,5 Women suffering from POF experience similar symptoms to natural menopause; however, these symptoms are also accompanied by an earlier loss of fertility. Therefore, women at risk of POF who delay childbearing until after their 30s may experience problems conceiving and carrying a pregnancy to full term.1 This loss of fertility can be due to an accelerated loss of follicles, an inability of the remaining follicles to respond to ovulatory signals, an initially reduced ovarian reserve at the time of birth, or a combination of all.2 As the development of POF occurs without any early discernible signs or symptoms, the diagnosis of POF currently occurs at the end stage of the disease, with a large proportion of these patients having not previously conceived before the time of diagnosis.2


The genetics of premature ovarian failure: current perspectives.

Chapman C, Cree L, Shelling AN - Int J Womens Health (2015)

A schematic representation of the process of folliculogenesis in the mammalian ovary from primordial follicles through to follicle ovulation and subsequent corpus luteum formation.Notes: Initial recruitment is gonadotropin independent and involves the differentiation of primordial follicles into primary and preantral follicles, the majority of which undergo atresia prior to puberty. Cyclic recruitment occurs after puberty and is gonadotropin dependent. Cyclic recruitment involves the growth and development of antral follicles through to mature preovulatory follicle selection and ovulation or atresia. This process continues throughout a female’s reproductive lifespan until the primordial follicle pool is depleted.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590549&req=5

f1-ijwh-7-799: A schematic representation of the process of folliculogenesis in the mammalian ovary from primordial follicles through to follicle ovulation and subsequent corpus luteum formation.Notes: Initial recruitment is gonadotropin independent and involves the differentiation of primordial follicles into primary and preantral follicles, the majority of which undergo atresia prior to puberty. Cyclic recruitment occurs after puberty and is gonadotropin dependent. Cyclic recruitment involves the growth and development of antral follicles through to mature preovulatory follicle selection and ovulation or atresia. This process continues throughout a female’s reproductive lifespan until the primordial follicle pool is depleted.
Mentions: The end of a woman’s reproductive lifespan is marked by the occurrence of menopause, defined as being the last menstruation that occurs for a woman, but is caused by the exhaustion of the ovarian reserve.1 In the general female population, across many ethnicities and over recent human history, the average age of natural menopause has remained at 50–52 years. However, aberrations in ovulatory processes, as outlined in Figure 1, may cause a pathogenic early depletion of ovarian follicles, which may result in premature menopause. Menopause before the age of 40 years is defined as premature ovarian failure (POF), also known as primary ovarian insufficiency.2 POF is described as the premature cessation of ovarian function and is characterized by 4–6 months of amenorrhea, a rise in serum follicle-stimulating hormone (FSH) levels to greater than 40 mIU/L, and hypoestrogenism.2,3 POF is a common disease, occurring in 1% of all women and 0.1% of women below the age of 30 years.2 As a consequence of hypoestrogenism, POF is associated with a greater risk of osteoporosis, osteoarthritis, and cardiovascular disease.4,5 Women suffering from POF experience similar symptoms to natural menopause; however, these symptoms are also accompanied by an earlier loss of fertility. Therefore, women at risk of POF who delay childbearing until after their 30s may experience problems conceiving and carrying a pregnancy to full term.1 This loss of fertility can be due to an accelerated loss of follicles, an inability of the remaining follicles to respond to ovulatory signals, an initially reduced ovarian reserve at the time of birth, or a combination of all.2 As the development of POF occurs without any early discernible signs or symptoms, the diagnosis of POF currently occurs at the end stage of the disease, with a large proportion of these patients having not previously conceived before the time of diagnosis.2

Bottom Line: The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF.Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF.The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

ABSTRACT
Premature ovarian failure (POF) is a common cause of infertility in women, characterized by amenorrhea, hypoestrogenism, and elevated gonadotropin levels in women under the age of 40. Many genes have been identified over the past few years that contribute to the development of POF. However, few genes have been identified that can explain a substantial proportion of cases of POF. The unbiased approaches of genome-wide association studies and next-generation sequencing technologies have identified several novel genes implicated in POF. As only a small proportion of genes influencing idiopathic POF have been identified thus far, it remains to be determined how many genes and molecular pathways may influence idiopathic POF development. However, owing to POF's diverse etiology and genetic heterogeneity, we expect to see the contribution of several new and novel molecular pathways that will greatly enhance our understanding of the regulation of ovarian function. Future genetic studies in large cohorts of well-defined, unrelated, idiopathic POF patients will provide a great opportunity to identify the missing heritability of idiopathic POF. The identification of several causative genes may allow for early detection and would provide better opportunity for early intervention, and furthermore, the identification of specific gene defects will help direct potential targets for future treatment.

No MeSH data available.


Related in: MedlinePlus