The ovarian stroma as a new frontier

Kinnear, Hadrian M; Tomaszewski, Claire E; Chang, Faith L; Moravek, Molly B.; Xu, Min; Padmanabhan, Vasantha; Shikanov, Ariella

doi:10.1530/rep-19-0501

Cited by 121 publications

(106 citation statements)

References 112 publications

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“…The pathophysiology of PCOS is complex and has long been controversial. PCOS may have multifactorial causes related to genetic, metabolic, fetal, and environmental factors [67][68][69][70][71][72][73]. There are several genes and pathways reported to be related to the PCOS phenomenon.…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

“…There are several genes and pathways reported to be related to the PCOS phenomenon. The followings are examples [68,71,73]. Anti-Müllerian hormone (AMH), a glycoprotein secreted by the granulosa cells of the pre-antral and small antral follicles, has an inhibitory effect on primordial follicle recruitment and high levels of expression in PCOS patients.…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

“…Intercellular adhesion molecule 1 (ICAM1) is a cell surface glycoprotein involved in integrins. The other cytokines, hormones or growth factors, and micro ribonucleic acids are also involved in the pathophysiology of PCOS, such as vascular epithelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), interleukin (IL), adipocytokine family (chemerin, omentin-1, leptin, adiponectin, and others), leptin, differentially expressed in normal and neoplastic development (DENND), RAS-related protein 5b (RAB5B), and small noncoding micro ribonucleic acid (microRNAs, miRNAs, and miR), including miR-130b-3p [68,71,73]. Since gene expression is controlled and modified by epigenetic factors, the post-translational modifications of proteins, such as methylation [74], acetylation [75], glycosylation [76], and sialylation [77], involved in turning the switch "on" or "off", are also reported to play a role in the pathophysiology of PCOS [71,73].…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

“…Several theories have been proposed to explain the pathogenesis of PCOS, often based on the concept that ovarian steroidogenesis requires gonadotropin stimulation and the subsequent dysregulation or dysfunction of the hormone, metabolism, and homeostasis systems, such as consequent unopposed estrogenemia, IR, compensatory hyperinsulinemia, chronic inflammatory reaction, proinflammatory cytokines, and oxidative stress [67][68][69]. The disturbance of the hypothalamic-pituitary-ovary (HPO) axis was first proposed in PCOS patients, because of its clear results [69].…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

“…The disturbance of the hypothalamic-pituitary-ovary (HPO) axis was first proposed in PCOS patients, because of its clear results [69]. In addition, dysfunction of the negative feedback effects of progesterone represents a key finding of the increased pulse frequency and amplitude of LH in patients with PCOS [68,69]. Coutinho and Kauffman concluded that a hyperactive GnRH neural circuit, including an increase in GnRH neuron activity, an increase in stimulatory gamma amino butyric acid (γ-aminobutyric acid, GABA)-ergic (GABAergic) innervation, and postsynaptic currents onto GnRH neurons, as well as an increased secretion of kisspeptin, favor a neuroendocrine basis for either the etiology or phenotype of PCOS [78].…”

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

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Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Seow¹,

Chang

Chen

et al. 2020

IJMS

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Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5–10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and many hypotheses have been proposed. Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5–15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, one particular surgical method, called laparoscopic ovarian drilling (LOD), has been proposed as an alternative treatment. LOD results in an overall spontaneous ovulation rate of 30–90% and final pregnancy rates of 13–88%. These benefits are more significant for women with CC-resistant PCOS. Although the intra- and post-operative complications and sequelae are always important, we believe that a better understanding of the pathophysiological changes and/or molecular mechanisms after LOD may provide a rationale for this procedure. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of “toxic” follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the “hypothalamus–pituitary–ovary” axis and subsequent spontaneous ovulation. The detailed local and systematic changes in PCOS women after LOD are comprehensively reviewed in the current article.

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Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Section: The Pathophysiology Of Polycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

See 3 more Smart Citations

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Seow¹,

Chang

Chen

et al. 2020

IJMS

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Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging

Zhou,

Guo,

Lin

et al. 2023

Advanced Science

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Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, the aging‐related cellular and molecular changes in human ovaries that occur during these reproductive years have not been elucidated. Here, single‐cell RNA sequencing (scRNA‐seq) of human ovaries is performed from different childbearing ages and reveals that the activation of the pyroptosis pathway increased with age, mainly in macrophages. The enrichment of pyroptotic macrophages leads to a switch from a tissue‐resident macrophage (TRM)‐involve immunoregulatory microenvironment in young ovaries to a pyroptotic monocyte‐derived macrophage (MDM)‐involved proinflammatory microenvironment in middle‐aged ovaries. This remolded ovarian immuno‐microenvironment further promotes stromal cell senescence and accelerated reproductive decline. This hypothesis is validated in a series of cell and animal experiments using GSDMD‐KO mice. In conclusion, the work expands the current understanding of the ovarian aging process by illustrating a pyroptotic macrophage‐involved immune mechanism, which has important implications for the development of novel strategies to delay senescence and promote reproductive health.

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Ovarian tissue cryopreservation and transplantation: a review on reactive oxygen species generation and antioxidant therapy

2023

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The ovarian stroma as a new frontier

Cited by 121 publications

References 112 publications

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Molecular Mechanisms of Laparoscopic Ovarian Drilling and Its Therapeutic Effects in Polycystic Ovary Syndrome

Single‐Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging

Ovarian tissue cryopreservation and transplantation: a review on reactive oxygen species generation and antioxidant therapy

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