Autophagy regulation of physiological and pathological processes in the female reproductive tract

Cao, Bin; Camden, Alison J.; Parnell, Lindsay A.; Mysorekar, Indira U.

doi:10.1111/aji.12650

Cited by 31 publications

(15 citation statements)

References 58 publications

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“…Our findings that cortisol degrades COL1A1 and COL3A1 through lysosome and proteasome pathways, respectively, appear to reconcile with previous studies showing that both ubiquitin-proteasome and autophagic lysosome pathways are activated during ROM (Cao et al 2017, Zhao et al 2017. Although collagens I and III comprise the backbone of the mesenchymal structure of the compact layer in the amnion, they may differ slightly in their functional roles in ECM remodeling.…”

Section: Discussionsupporting

confidence: 88%

Proteasome-mediated degradation of collagen III by cortisol in amnion fibroblasts

Wang

et al. 2018

Journal of Molecular Endocrinology

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Rupture of fetal membranes (ROM) can initiate parturition at both term and preterm. Collagen III in the compact layer of the amnion contributes to the tensile strength of fetal membranes. However, the upstream signals triggering collagen III degradation remain mostly elusive. In this study, we investigated the role of cortisol regenerated by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in collagen III degradation in human amnion fibroblasts with an aim to seek novel targets for the prevention of preterm premature ROM (pPROM)-elicited preterm birth. Human amnion tissue and cultured amnion tissue explants and amnion fibroblasts were used to study the regulation of collagen III, which is composed of three identical 3α 1 chains (COL3A1), by cortisol. Cortisol decreased COL3A1 protein but not mRNA abundance in a concentration-dependent manner. Cortisone also decreased COL3A1 protein, which was blocked by 11β-HSD1 inhibition. The reduction in COL3A1 protein by cortisol was not affected by a transcription inhibitor but was further enhanced by a translation inhibitor. Autophagic pathway inhibitor chloroquine or siRNA-mediated knock-down of ATG7, an essential protein for autophagy, failed to block cortisol-induced reduction in COL3A1 protein abundance, whereas proteasome pathway inhibitors MG132 and bortezomib significantly attenuated cortisol-induced reduction in COL3A1 protein abundance. Moreover, cortisol increased COL3A1 ubiquitination and the reduction of COL3A1 protein by cortisol was blocked by PYR-41, a ubiquitin-activating enzyme inhibitor. Conclusively, cortisol regenerated in amnion fibroblasts may be associated with ROM at parturition by reducing collagen III protein abundance through a ubiquitin-proteasome pathway.

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Section: Discussionsupporting

confidence: 88%

Proteasome-mediated degradation of collagen III by cortisol in amnion fibroblasts

Wang

et al. 2018

Journal of Molecular Endocrinology

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“…The exact mechanisms of the mild shedding of the EGX in healthy ovulatory women and the tremendous shedding observed in pregnancy is presently unknown; however, it can be assumed that inflammatory processes may be responsible factors . It has already been demonstrated that endotoxin, ischemia reperfusion, atrial natriuretic peptide, BNP, tumor necrosis factor‐alpha, and activated leukocytes, which can induce the expression of heparanases and oxygen radicals, can lead to a destruction of the EGX.…”

Section: Discussionmentioning

confidence: 99%

The CYCLOCALYX study: Ovulatory cycle affects circulating compartments of the endothelial glycocalyx in blood

Hulde

Rogenhofer

Brettner

et al. 2017

American J Rep Immunol

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“…Autophagy is a non-apoptotic form of over-activated programmed cell death [27,28]. Autophagy plays an indispensable role in early embryonic development, which is often associated with abortion, preeclampsia, intrauterine growth restriction and other pathological pregnancies [29][30][31]. In this study, we detected the level of autophagy in villi of RSA patients was significantly lower than that of normal abortion patients.…”

Section: Discussionmentioning

confidence: 64%

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

Tan¹

Yang1

Wang

et al. 2019

Preprint

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Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies have reported autophagy can induce immune tolerance at the maternal fetal interface, but the mechanism is largely unclear. Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. In vivo and in vitro, the expression of killer molecules in NK cells was analyzed by flow cytometry (FCM). And the invasiveness of trophoblasts was tested by Cell invasion assay. Results: Compared with normal abortion patients, the level of autophagy in the villi of RSA patients was significantly decreased. In vitro experiments indicated that co-culture with autophagy suppression of trophoblasts (3-MA-pretreated trophoblasts) increased cytotoxicity of NK cell, which was mediated by the upregulation of insulin-like growth factor-2 (IGF-2). Meanwhile, autophagy suppression of trophoblasts led to a low level of Paternally Expressed Gene 10 (PEG10), leading to impaired cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. Injection with 3-MA in vivo , the cytotoxicity of uterine NK cells in pregnant mice and the embryo absorption rate were significantly increased. Conclusion: Autophagy suppression of trophoblasts should increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.

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Autophagy regulation of physiological and pathological processes in the female reproductive tract

Cited by 31 publications

References 58 publications

Proteasome-mediated degradation of collagen III by cortisol in amnion fibroblasts

Proteasome-mediated degradation of collagen III by cortisol in amnion fibroblasts

The CYCLOCALYX study: Ovulatory cycle affects circulating compartments of the endothelial glycocalyx in blood

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion

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