Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

Shen, Hui‐Hui; Zhang, Tao; Yang, Hui‐Li; Lai, Zhen‐Zhen; Zhou, Wen‐Jie; Mei, Jie; Shi, Jing; Zhu, Rui; Xu, Feng-Yuan; Li, Da‐Jin; Ye, Jiang‐Feng; Li, Ming‐Qing

doi:10.7150/thno.55241

Cited by 55 publications

(44 citation statements)

References 155 publications

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“…The current consensus is that the function of immune-related (including NK) cells is impaired. The role of NK cells in the removal of menstrual debris and endometrial fragments that are likely to reach the peritoneal cavity by retrograde menses has been studied extensively ( 140 ). Most studies have focused on the change of number of pNK cells and NK cells in peritoneal fluid.…”

Section: The Role Of Dnk Cells In Pathological Pregnancymentioning

confidence: 99%

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Zhang

Wei

2021

Front. Immunol.

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Pregnancy is a unique type of immunological process. Healthy pregnancy is associated with a series of inflammatory events: implantation (inflammation), gestation (anti-inflammation), and parturition (inflammation). As the most abundant leukocytes during pregnancy, natural killer (NK) cells are recruited and activated by ovarian hormones and have pivotal roles throughout pregnancy. During the first trimester, NK cells represent up to 50–70% of decidua lymphocytes. Differently from peripheral-blood NK cells, decidual natural killer (dNK) cells are poorly cytolytic, and they release cytokines/chemokines that induce trophoblast invasion, tissue remodeling, embryonic development, and placentation. NK cells can also shift to a cytotoxic identity and carry out immune defense if infected in utero by pathogens. At late gestation, premature activation of NK cells can lead to a breakdown of tolerance of the maternal–fetal interface and, subsequently, can result in preterm birth. This review is focused on the role of dNK cells in normal pregnancy and pathological pregnancy, including preeclampsia, recurrent spontaneous abortion, endometriosis, and recurrent implantation failure. dNK cells could be targets for the treatment of pregnancy complications.

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Section: The Role Of Dnk Cells In Pathological Pregnancymentioning

confidence: 99%

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Zhang

Wei

2021

Front. Immunol.

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“…Several papers evidence the role of autophagy in the progression and development of endometriosis [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. In a mouse model of surgically induced endometriosis, ectopic lesions revealed increased levels of autophagy-related protein 9A (ATG9A), an autophagic protein involved in vesicle formation [ 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, it has been demonstrated by in vivo experiments that during endometriosis, the inhibition of autophagy by increasing extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR) and serine/threonine kinase (AKT)/mTOR activity further downregulates apoptosis [ 27 ]. Endometriotic lesions from patients revealed decreased expressions of pro-apoptotic factors and increased expressions of anti-apoptotic factors when compared with healthy women [ 17 , 28 ]. Impaired apoptosis further contributes to the survival of endometrial cells into the peritoneal cavity and establishment of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis

Siracusa

D’Amico

Impellizzeri

et al. 2021

IJMS

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Endometriosis is a gynecological condition affecting patients in reproductive age. The aim of this paper was to assess the effects of the autophagy and mitophagy induction in a rat model of endometriosis. Endometriosis was induced by the injection of uterine fragments, and rapamycin (0. 5 mg/kg) was administered once per week. One week from the induction, rats were sacrificed, and laparotomy was performed to collect the endometriotic implants and to further process them for molecular analysis. Western blot analysis was conducted on explanted lesions to evaluate the autophagy pathway during the pathology. Elevated phospho-serine/threonine kinase (p-AKT) and mammalian target of rapamycin (mTOR) expressions were detected in vehicle-treated rats, while Beclin and microtubule-associated protein 1A/1B-light chain 3 II (LC3II) expressions were low. Additionally, samples collected from vehicle groups indicated low Bnip3, Ambra1, and Parkin expressions, demonstrating impaired autophagy and mitophagy. Rapamycin administration reduced p-AKT and mTOR expressions and increased Beclin and LC3II, Bnip3, Ambra1, and Parkin expressions, activating both mechanisms. We also evaluated the impact of the impaired autophagy and mitophagy pathways on apoptosis and angiogenesis. Rapamycin was administered by activating autophagy and mitophagy, which increased apoptosis (assessed by Western blot analysis of Bcl-2, Bax, and Cleaved-caspase 3) and reduced angiogenesis (assessed by immunohistochemical analysis of vascular endothelial grow factor (VEGF) and CD34) in the lesions. All of these mechanisms activated by the induction of the autophagy and mitophagy pathways led to the reduction in the lesions’ volume, area and diameter.

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“…The endocrine system of multicellular organisms comprises secretory glands that release hormones that can regulate signal transduction pathways with exquisite specificity upon paracrine engagement with a specific cognate receptor in the target cells. These interactions lead to the modulation of a vast set of functions, including but not limited to energy balance metabolism, body weight regulation, growth development, reproduction, and immunity ( 1 , 2 ). Alterations of the natural endocrine hormonal homeostatic balance eventually occur through the exposure to environmental single or mixed synthetic chemical pollutants exhibiting hormone-mimetic activities, collectively regarded as endocrine disruptor compounds (EDCs) ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

Vaccination of Gilthead Seabream After Continuous Xenoestrogen Oral Exposure Enhances the Gut Endobolome and Immune Status via GPER1

et al. 2021

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In fish culture settings, the exogenous input of steroids is a matter of concern. Recently, we unveiled that in the gilthead seabream (Sparus aurata), the G protein-coupled estrogen receptor agonist G-1 (G1) and the endocrine disruptor 17α-ethinylestradiol (EE2) are potent modulators in polyreactive antibody production. However, the integral role of the microbiota upon immunity and antibody processing in response to the effect of EE2 remains largely unexplored. Here, juvenile seabreams continuously exposed for 84 days to oral G1 or EE2 mixed in the fish food were intraperitoneally (i.p.) immune primed on day 42 with the model antigen keyhole limpet hemocyanin (KLH). A critical panel of systemic and mucosal immune markers, serum VTG, and humoral, enzymatic, and bacteriolytic activities were recorded and correlated with gut bacterial metagenomic analysis 1 day post-priming (dpp). Besides, at 15 dpp, animals received a boost to investigate the possible generation of specific anti-KLH antibodies at the systemic and mucosal interphases by the end of the trial. On day 43, EE2 but not G1 induced a significant shift in the serum VTG level of naive fish. Simultaneously, significant changes in some immune enzymatic activities in the serum and gut mucus of the EE2-treated group were recorded. In comparison, the vaccine priming immunization resulted in an attenuated profile of most enzymatic activities in the same group. The gut genes qPCR analysis exhibited a related pattern, only emphasized by a significant shift in the EE2 group’s il1b expression. The gut bacterial microbiome status underwent 16S rRNA dynamic changes in alpha diversity indices, only with the exposure to oral G1, supporting functional alterations on cellular processes, signaling, and lipid metabolism in the microbiota. By the same token, the immunization elevated the relative abundance of Fusobacteria only in the control group, while this phylum was depleted in both the treated groups. Remarkably, the immunization also promoted changes in the bacterial class Betaproteobacteria and the estrogen-associated genus Novosphingobium. Furthermore, systemic and mucosal KLH-specific immunoglobulin (Ig)M and IgT levels in the fully vaccinated fish showed only slight changes 84 days post-estrogenic oral administration. In summary, our results highlight the intrinsic relationship among estrogens, their associated receptors, and immunization in the ubiquitous fish immune regulation and the subtle but significant crosstalk with the gut endobolome.

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Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis

Cited by 55 publications

References 155 publications

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications

Autophagy and Mitophagy Promotion in a Rat Model of Endometriosis

Vaccination of Gilthead Seabream After Continuous Xenoestrogen Oral Exposure Enhances the Gut Endobolome and Immune Status via GPER1

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