The estrogen–macrophage interplay in the homeostasis of the female reproductive tract

Pepe, Giovanna; Locati, Massimo; Torre, Sara Della; Mornata, Federica; Cignarella, Andrea; Maggi, Adriana; Vegeto, Elisabetta

doi:10.1093/humupd/dmy026

Cited by 40 publications

(37 citation statements)

References 268 publications

(310 reference statements)

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“…Ovarian macrophages have received ongoing attention with regard to their role in reproductive homeostasis and their regulation by estrogen (reviewed in Wu et al 2004, Pepe et al 2018. Ovaries may contain multiple macrophage subsets, and phenotypes can range from classical inflammatory (M1) to alternative tissue remodeling (M2) during different parts of the ovarian cycle (Carlock et al 2013, Pepe et al 2018. Increased proportions of M2 macrophages, monocyte-derived macrophages, and multinucleated macrophages have been seen with murine ovarian aging (Briley et al 2016.…”

Section: Immune Cellsmentioning

confidence: 99%

The ovarian stroma as a new frontier

et al. 2020

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Historically, research in ovarian biology has focused on folliculogenesis, but recently the ovarian stroma has become an exciting new frontier for research, holding critical keys to understanding complex ovarian dynamics. Ovarian follicles, which are the functional units of the ovary, comprise the ovarian parenchyma, while the ovarian stroma thus refers to the inverse, or the components of the ovary that are not ovarian follicles. The ovarian stroma includes more general components such as immune cells, blood vessels, nerves, and lymphatic vessels, as well as ovary-specific components including ovarian surface epithelium, tunica albuginea, intraovarian rete ovarii, hilar cells, stem cells, and a majority of incompletely characterized stromal cells including the fibroblast-like, spindle-shaped, and interstitial cells. The stroma also includes ovarian extracellular matrix components. This review combines foundational and emerging scholarship regarding the structures and roles of the different components of the ovarian stroma in normal physiology. This is followed by a discussion of key areas for further research regarding the ovarian stroma, including elucidating theca cell origins, understanding stromal cell hormone production and responsiveness, investigating pathological conditions such as polycystic ovary syndrome (PCOS), developing artificial ovary technology, and using technological advances to further delineate the multiple stromal cell types.

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Section: Immune Cellsmentioning

confidence: 99%

The ovarian stroma as a new frontier

et al. 2020

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“…Macrophages are present in almost every tissue or organ system including the barriers system comprising of respiratory tract (pulmonary alveolar and interstitial macrophages), skin, gastrointestinal tract (GIT), and reproductive tract [82][83][84][85][86][87][88][89][90][91]. Thus their presence in the every organ system along with the mucosal sites serving as potential sites for the entry of pathogens, toxins, allergens and xenobiotics makes them first line of defense.…”

Section: Role Of Monocytes and Macrophages In Host Defensementioning

confidence: 99%

Macrophages: The Potent Immunoregulatory Innate Immune Cells

Kumar¹

2020

Macrophage Activation - Biology and Disease

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Macrophages are ubiquitously present innate immune cells in humans and animals belonging to both invertebrates and vertebrates. These cells were first recognized by Elia Metchnikoff in 1882 in the larvae of starfish upon insertion of thorns of tangerine tree and later in Daphnia magna or common water flea infected with fungal spores as cells responsible for the process of phagocytosis of foreign particles. Elia Metchnikoff received the Noble prize (Physiology and Medicine) for his discovery and describing the process of phagocytosis in 1908. More than 130 years have passed and different subtypes and roles of macrophages as innate immune cells have been established by the researchers. In addition to their immunoregulatory role in immune homeostasis and pathogenic infection, they also play a crucial role in the pathogenesis of sterile inflammatory conditions including autoimmunity, obesity, and cancer. The present chapter describes the immunoregulatory role of macrophages in the homeostasis and inflammatory diseases varying from autoimmunity to metabolic diseases including obesity.

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“…Similarly, Inhba, Gdnf, and Grem1, besides linking the follicle/oocyte and immune/inflammatory themes, exhibit a transcriptional modulation activity and take part in the cytokine-like gene regulatory network ( Figure 5B). The presence of immune cells in the ovary, with macrophages as the more abundant, is inherent to various physiological processes during fertile life, including follicle maturation, ovulation, luteogenesis/luteolysis, atresia, and vascular integrity [27][28][29]. As follicle depletion and ovarian aging progress, this immune cell content and their activities would become modulated by the SASP effect.…”

Section: Parity-dependent Serum Cytokine Levels and Correlation With mentioning

confidence: 99%

“…Ovarian processes, including ovulation, luteinization, and atresia, depend on a delicate pro-/anti-inflammatory balance relying on leukocyte activities [27][28][29]58]. Macrophages are the most abundant ovarian leukocytes, and their function in the ovary and other sections of the female reproductive system during fertile age is modulated by estrogens to induce the alternative, M2 anti-inflammatory, tissue repair differentiation profile [29]. The available information about ovarian immunity and inflammation during the postmenopausal phase and parity history is scarce.…”

Section: Parity History Improves the Ovarian And Systemic Immune-chemmentioning

confidence: 99%

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

et al. 2020

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In middle-aged women, the decline of ovarian follicle reserve below a critical threshold marks menopause, leading to hormonal, inflammatory, and metabolic changes linked to disease. The highest incidence and mortality of sporadic ovarian cancer (OC) occur at post-menopause, while OC risk is reduced by full-term pregnancies during former fertile life. Herein, we investigate how parity history modulates the ovarian transcriptome related to such declining follicle pool and systemic inflammation in reproductively-aged mice. Female C57BL/6 mice were housed under multiparous and virgin (nulliparous) breeding regimens from adulthood until estropause. The ovaries were then subjected to follicle count and transcriptional profiling, while a cytokine panel was determined in the sera. As expected, the follicle number was markedly decreased just by aging. Importantly, a significantly higher count of primordial and total follicles was observed in aged multiparous relative to aged virgin ovaries. Consistently, among the 65 genes of higher expression in aged multiparous ovaries, 27 showed a follicle count-like pattern, 21 had traceable evidence of roles in follicular/oocyte homeostasis, and 7 were transforming-growth factor beta (TGF-β)/bone morphogenetic protein (BMP) superfamily members. The remaining genes were enriched in cell chemotaxis and innate-immunity, and resembled the profiles of circulating CXCL1, CXCL2, CXCL5, CSF3, and CCL3, chemokines detected at higher levels in aged multiparous mice. We conclude that multiparity during reproductive life promotes the retention of follicle remnants while improving local (ovarian) and systemic immune-innate surveillance in aged female mice. These findings could underlie the mechanisms by which pregnancy promotes the long-term reduced OC risk observed at post-menopause.

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The estrogen–macrophage interplay in the homeostasis of the female reproductive tract

Cited by 40 publications

References 268 publications

The ovarian stroma as a new frontier

The ovarian stroma as a new frontier

Macrophages: The Potent Immunoregulatory Innate Immune Cells

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

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