Polycystic ovary syndrome Franks, Stephen
Medicine (Abingdon. 1995, UK ed.),
September 2021, 2021-09-00, Letnik:
49, Številka:
9
Journal Article
Recenzirano
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. It typically presents with symptoms of anovulation associated with clinical and/or biochemical evidence of androgen ...excess, although its spectrum of presentation includes women with hyperandrogenism who have regular periods. It is the most common cause of anovulatory infertility, and is now recognized as a major risk factor for the development of type 2 diabetes mellitus. Its aetiology remains unclear, but both genetic and environmental factors are involved. Typical biochemical features are raised serum concentrations of testosterone and luteinizing hormone, particularly in anovulatory women, but the diagnosis is made primarily on clinical criteria. It is now recognized that women with PCOS commonly have anxiety and depression, and reduced quality of life indices. Management of PCOS includes treatment of infertility, menstrual regulation in women who do not desire pregnancy and treatment of associated symptoms of hyperandrogenism. Other important aspects of management are diet and lifestyle changes for overweight and obese women with PCOS and attention to psychological health.
The postnatal mouse ovary is rich in quiescent and early-growing oocytes, each one surrounded by a layer of somatic granulosa cells (GCs) on a basal lamina. As oocytes start to grow the GCs change ...shape from flattened to cuboidal, increase their proliferation and form multiple layers, providing a unique model for studying the relationship between cell shape, proliferation and multilayering within the context of two different intercommunicating cell types: somatic and germ cells. Proliferation of GCs was quantified using immunohistochemistry for Ki67 and demonstrated that, unusually, cuboidal cells divided more than flat cells. As a second layer of GCs started to appear, cells on the basal lamina reached maximum packing density and the axes of their mitoses became perpendicular to the basal lamina, resulting in cells dividing inwards to form second and subsequent layers. Proliferation of basal GCs was less than that of inner cells. Ultrastructurally, collagen fibrils outside the basal lamina became more numerous as follicles developed. We propose that the basement membrane and/or theca cells that surround the follicle provide an important confinement for rapidly dividing columnar cells so that they attain maximum packing density, which restricts lateral mitosis and promotes inwardly oriented cell divisions and subsequent multilayering.
The dopamine transporter (DAT) regulates the dimension and duration of dopamine transmission. DAT expression, its trafficking, protein-protein interactions, and its activity are conventionally ...studied in the CNS and within the context of neurological diseases such as Parkinson's Diseases and neuropsychiatric diseases such as drug addiction, attention deficit hyperactivity and autism. However, DAT is also expressed at the plasma membrane of peripheral immune cells such as monocytes, macrophages, T-cells, and B-cells. DAT activity via an autocrine/paracrine signaling loop regulates macrophage responses to immune stimulation. In a recent study, we identified an immunosuppressive function for DAT, where blockade of DAT activity enhanced LPS-mediated production of IL-6, TNF-α, and mitochondrial superoxide levels, demonstrating that DAT activity regulates macrophage immune responses. In the current study, we tested the hypothesis that in the DAT knockout mice, innate and adaptive immunity are perturbed. We found that genetic deletion of DAT (DAT
) results in an exaggerated baseline inflammatory phenotype in peripheral circulating myeloid cells. In peritoneal macrophages obtained from DAT
mice, we identified increased MHC-II expression and exaggerated phagocytic response to LPS-induced immune stimulation, suppressed T-cell populations at baseline and following systemic endotoxemia and exaggerated memory B cell expansion. In DAT
mice, norepinephrine and dopamine levels are increased in spleen and thymus, but not in circulating serum. These findings in conjunction with spleen hypoplasia, increased splenic myeloid cells, and elevated MHC-II expression, in DAT
mice further support a critical role for DAT activity in peripheral immunity. While the current study is only focused on identifying the role of DAT in peripheral immunity, our data point to a much broader implication of DAT activity than previously thought. This study is dedicated to the memory of Dr. Marc Caron who has left an indelible mark in the dopamine transporter field.
Follicle-Stimulating Hormone (FSH) at a wide range of doses is routinely added to culture media during in vitro maturation
(IVM) of oocytes, but the effects on oocyte health are unclear. The ...suggestion that superovulation may cause aneuploidy and
fetal abnormalities prompted us to study the potential role of FSH in the genesis of chromosomal abnormalities during meiosis
I. Mouse cumulus-oocyte complexes (COCs) isolated from the antral follicles of unprimed, sexually immature B6CBF 1 mice were cultured in increasing concentrations of FSH. Following culture, matured oocytes were isolated, spread, stained
with DAPI, and the numbers of chromosomes counted. Significantly increased aneuploidy, arising during the first meiotic division,
was observed in metaphase II oocytes matured in higher concentrations of FSH (â¥20 ng/ml). The effect of FSH on spindle morphology
and chromosome alignment during metaphase I was then explored using immunocytochemistry and three-dimensional reconstruction
of confocal sections. High FSH had no effect on gross spindle morphology but did alter chromosome congression during prometaphase
and metaphase, with the spread of chromosomes across the spindle at this time being significantly greater in oocytes cultured
in 2000 ng/ml compared with 2 ng/ml FSH. Analysis of three-dimensional reconstructions of spindles in oocytes matured in 2000
ng/ml FSH shows that chromosomes are more scattered and farther apart than they are following maturation in 2 ng/ml FSH. These
results demonstrate that exposure to high levels of FSH during IVM can accelerate nuclear maturation and induce chromosomal
abnormalities and highlights the importance of the judicious use of FSH during IVM.
Abstract
Hormonal treatment can affect chromosome behavior of oocytes matured in vitro
Summary
Polycystic ovary syndrome (PCOS) is associated with insulin resistance and an increased risk of developing type 2 diabetes mellitus. The attendant hyperinsulinaemia is also thought to ...contribute to the mechanism of anovulation in PCOS. Both metabolic and reproductive abnormalities are amplified by obesity and the treatment of first choice for overweight or obese women with PCOS is modification of diet and lifestyle. Nevertheless, changes in diet and exercise are, for many subjects, not easy to sustain and there seems an obvious place for insulin sensitizing agents in management of both reproductive and metabolic disturbances. Of the available agents affecting insulin sensitivity, metformin has been the most widely used but despite an enormous literature reporting beneficial effects on reproductive, cutaneous and metabolic manifestations of PCOS, its efficacy is unproven apart from in those subjects with impaired glucose tolerance or frank diabetes. Metformin at least has an assured safety record whereas both efficacy and safety of other insulin sensitizing agents in women of reproductive age, such as thiazolidinediones and glucagon‐like peptide analogues, remains to be established.
Polycystic ovary syndrome (PCOS) is a common female condition typified by reproductive, hyperandrogenic, and metabolic features. Polycystic ovary syndrome is a genetic condition, exacerbated by ...obesity. There is a close link between obesity and PCOS based on epidemiological data, and more recently corroborated through genetic studies. There are many mechanisms mediating the effects of weight-gain and obesity on the development of PCOS. The metabolic effects of insulin resistance and steroidogenic and reproductive effects of hyperinsulinaemia are important mechanisms. Adipokine production by subcutaneous and visceral fat appears to play a part in metabolic function. However, given the complexity of PCOS pathogenesis, it is important also to consider possible effects of PCOS on further weight-gain, or at least on hampering attempts at weight-loss and maintenance through lifestyle changes. Possible mediators of these effects include changes in energy expenditure, mental ill health, or physical inactivity. In this brief review, we discuss the main mechanisms that underlie the association between obesity and PCOS, from divergent perspectives of weight-gain contributing to development of PCOS and vice versa. We also consider novel management options for women with obesity and PCOS.
Androgen production by the ovary fulfils an essential physiological role, not only in providing substrate for oestrogen production but also by playing an important part in the normal growth and ...maturation of the ovarian follicle. Excess androgen production is a cardinal feature of polycystic ovary syndrome, a major cause of ovulatory and metabolic dysfunction in women. This review focuses on recent data that shed light on the molecular and cellular mechanisms involved in both normal and excess androgen production. It also includes a summary of recent advances in understanding the impact of androgens on ovarian function in normal and polycystic ovaries.
Anovulation in women with polycystic ovary syndrome (PCOS) is characterised by arrested growth of antral follicles. A relative lack of FSH may contribute to the persistence of anovulation but is ...unlikely, by itself, to be a major cause of it. Granulosa cells from anovulatory women with polycystic ovaries hypersecrete oestradiol, compared with size-matched follicles from normal ovaries or polycystic ovaries from ovulatory women. This phenomenon appears to reflect a condition of advanced maturation of medium-sized antral follicles. The underlying basis for the abnormalities in anovulatory PCOS remains uncertain, but it is possible that there are intrinsic differences in folliculogenesis between polycystic and normal ovaries which affect preantral as well as antral follicles. An alternative — but not mutually exclusive — explanation of this disorder is the abnormal endocrine environment. Hypersecretion of both LH and insulin are typical of anovulatory women with PCOS. Studies in isolated granulosa cells, have shown, that insulin greatly augments the action of LH on steroidogenesis but this interaction may compromise further growth of medium-sized antral follicles by generation of ‘preovulatory’ concentrations of cAMP within the granulosa cell and thereby leading, prematurely, to terminal differentiation of granulosa cells.
Summary
We have recently proposed that polycystic ovary syndrome (PCOS) has its origin in fetal life. This hypothesis is based on data from animal models (rhesus monkey or sheep that have been ...exposed prenatally to high doses of androgen) and is supported by clinical studies. It is suggested that, in human females, exposure to excess androgen, at any stage from fetal development of the ovary to the onset of puberty, leads to many of the characteristic features of PCOS, including abnormalities of luteinizing hormone secretion and insulin resistance. It is likely that, in humans with PCOS, the development of the PCOS phenotype results primarily from a genetic predisposition for the fetal ovary to hypersecrete androgen. At present, it is unclear whether the maternal environment directly influences the development of PCOS in the offspring. Maternal androgen excess is unlikely to affect the fetus, because the placenta presents an effective barrier, but metabolic disturbances during pregnancy could affect development of the syndrome in the fetus. In postnatal life, the natural history of PCOS can be further modified by factors affecting insulin secretion and/or action, most importantly, nutrition. We now have evidence for a disorder of early follicular development in the polycystic ovary that is consistent with an increased population of primordial follicles in the fetal ovary. It remains to be determined whether this phenomenon is the cause or the effect of increased exposure to androgen within the ovary. PCOS is the commonest endocrine disorder in women. It is not only a very prevalent cause of anovulatory infertility, menstrual disturbances and hirsutism, but it is also a major risk factor for the development of type 2 diabetes mellitus in later life. The aetiology of the syndrome remains uncertain but there is increasing evidence for a genetic basis. PCOS very often becomes clinically manifest during adolescence with maturation of the hypothalamic‐pituitary‐ovarian axis but the genesis of the syndrome may be during very early development – perhaps even in utero. In this review, this hypothesis is explored in the light of clinical, biochemical and genetic research.
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