Menstrual cycle-dependent changes of Toll-like receptors in endometrium

Aflatoonian, Reza; Tuckerman, E.; Elliott, Sarah; Bruce, Chris; Aflatoonian, Abbas; Li, T.C.; Fazeli, Alireza

doi:10.1093/humrep/del388

Cited by 98 publications

(106 citation statements)

References 51 publications

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“…In view of the significant increase in steady-state levels of both TLR7 and TLR8 mRNAs in uteri of early pregnant ewes, we determined cell-specific expression of TLR7 and TLR8 proteins to be particularly abundant in uterine LE and sGE and expressed in a temporal and cell-specific manner that differed due to reproductive TLR and establishment of pregnancy in sheep status, which supports results obtained from previous studies (Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007. The uterine epithelia constitute a primary barrier against pathogens, while also ensuring tolerance to the implanting conceptus and producing nutrients and adhesion molecules indispensable for pregnancy (Burghardt et al 2002, Gray et al 2006.…”

Section: Discussionsupporting

confidence: 83%

“…The abundance of TLRs was maximum in the endometrium between Days 12 and 14 of the estrous cycle and pregnancy, but then decreased on Day 16 in cyclic ewes while remaining similar in abundance in pregnant ewes. This suggests that progesterone influences expression of TLRs as proposed for other species (Jorgenson et al 2005, Aflatoonian et al 2007). Production of progesterone by ovine CL is maximal between Days 9 and 10 of the estrous cycle.…”

Section: Discussionsupporting

confidence: 52%

“…The increase in expression of TLR2, TLR7, TLR8, and TLR9 in the endometrium during early pregnancy probably results from both progesterone-dependent recruitment of immune cells enriched in these particular TLRs (Segerson et al 1991, Plaks et al 2008, Gomez-Lopez et al 2010, Mansouri-Attia et al 2012 and changes in uterine gene expression required for pregnancy (Young et al 2004, Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007, Turner et al 2012. In view of the significant increase in steady-state levels of both TLR7 and TLR8 mRNAs in uteri of early pregnant ewes, we determined cell-specific expression of TLR7 and TLR8 proteins to be particularly abundant in uterine LE and sGE and expressed in a temporal and cell-specific manner that differed due to reproductive TLR and establishment of pregnancy in sheep status, which supports results obtained from previous studies (Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, human endometrial epithelia and stromal cells express TLR1-TLR10, with higher levels during the progesterone-dominated secretory phase of the menstrual cycle (Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007). Moreover, a microarray analysis found significant up-regulation of genes involved in the TLR pathway in the mouse uterus during the implantation period (Pan et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Ruiz-Gonzalez¹,

Minten²,

Wang³

et al. 2015

Reproduction

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Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction.In Study 1, we demonstrated that abundance of ovine TLR1-TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1-TLR3, TLR5-TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1-TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Ruiz-Gonzalez¹,

Minten²,

Wang³

et al. 2015

Reproduction

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“…TLRs 1-10 are expressed in the female reproductive tract (Darville et al 2003, Pioli et al 2004, Aflatoonian et al 2007). Vaginal epithelial cell lines have been shown to express TLR1-3, TLR5 and TLR6, and primary endocervical epithelial cells have been shown to express TLR1-3 and TLR6 (Fichorova et al 2002).…”

Section: Toll-like Receptors (Tlrs)mentioning

confidence: 99%

Innate immunity and disorders of the female reproductive tract

Horne¹,

Stock²,

King³

2008

Reproduction

137

129

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Sexually transmitted infections, and their associated sequelae, such as tubal infertility, ectopic pregnancy and preterm labour, are a major worldwide health problem. Chlamydia trachomatis infection is thought to be the leading global cause of tubal infertility and tubal ectopic pregnancy. Preterm birth occurs in around 10% of all deliveries, and nearly 30% of preterm deliveries are associated with intrauterine infection. The mucosal innate immune system of the female reproductive tract has evolved to eliminate such sexually transmitted pathogens whilst maintaining its ability to accommodate specialized physiological functions that include menstruation, fertilization, implantation, pregnancy and parturition. The aim of this review was to describe the role and distribution of key mediators of the innate immune system, the natural antimicrobial peptides (secretory leukocyte protease inhibitor, elafin and the defensins) and the pattern recognition toll-like receptors in the normal female reproductive tract and in the context of these pathological processes.

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Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model

Xiao

Shi

Han

et al. 2018

Drug Development Research

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Primary dysmenorrhea affects the quality of life in young women, particularly school and work performance. This study investigated the mechanisms of penehyclidine hydrochloride (PHC) efficacy on a rat model of primary dysmenorrhea. The model was induced by injecting both estradiol benzoate and oxytocin. Different doses of PHC were administrated intraperitoneally following estradiol benzoate administration. Writhing scores were assessed, and pathological changes of the uterus were observed via hematoxylin and eosin staining. Western blot and real‐time PCR were used to evaluate the expression level of the M3 receptor, both TLR3 and TLR4 in uterine tissue, and the level of Ca2+ was measured in uterine tissues. Writhing scores significantly decreased in the PHC treatment group compared to model, and PHC alleviated the occurrence of edema or necrosis in the uteri compared to model group. PHC can decrease the M3 receptor, TLR3, TLR4 expression, and the Ca2+ level compared to the model group. PHC is a potential candidate for the future treatment of primary dysmenorrhea due to its ability to attenuate muscarinic receptors and TLRs. Preclinical Research & Development

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Menstrual cycle-dependent changes of Toll-like receptors in endometrium

Abstract: TLR7-10 localization is not limited to endometrial epithelium but is also present in the stroma of the endometrial tissue. Endometrial TLR2-6, 9 and 10 genes are cyclically expressed during the menstrual cycle.

Cited by 98 publications

References 51 publications

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Innate immunity and disorders of the female reproductive tract

Mechanism of penehyclidine hydrochloride on a dysmenorrhea rat model

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