Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization

Achache, Hanna; Tsafrir, Avi; Prus, Diana; Reich, Reuven; Revel, Ariel

doi:10.1016/j.fertnstert.2009.07.1668

Cited by 124 publications

(81 citation statements)

References 33 publications

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“…In in vitro fertilization (IVF), endometrial thickness is highly correlated with the success rate of implantation and pregnancy (Noyes et al , 1995; Lim & Wang, 2010). Interestingly, patients with recurrent implantation failure in IVF treatment have reduced LPA 3 levels (Achache et al , 2010). Thus, treatment of human females with an LPA 3 agonist may increase the pregnancy rate by promoting the endometrial cell growth and increasing the endometrial thickness in IVF.…”

Section: Discussionmentioning

confidence: 99%

Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways

et al. 2017

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During pregnancy, up‐regulation of heparin‐binding (HB‐) EGF and cyclooxygenase‐2 (COX‐2) in the uterine epithelium contributes to decidualization, a series of uterine morphological changes required for placental formation and fetal development. Here, we report a key role for the lipid mediator lysophosphatidic acid (LPA) in decidualization, acting through its G‐protein‐coupled receptor LPA 3 in the uterine epithelium. Knockout of Lpar3 or inhibition of the LPA‐producing enzyme autotaxin (ATX) in pregnant mice leads to HB‐EGF and COX‐2 down‐regulation near embryos and attenuates decidual reactions. Conversely, selective pharmacological activation of LPA 3 induces decidualization via up‐regulation of HB‐EGF and COX‐2. ATX and its substrate lysophosphatidylcholine can be detected in the uterine epithelium and in pre‐implantation‐stage embryos, respectively. Our results indicate that ATX–LPA–LPA 3 signaling at the embryo‐epithelial boundary induces decidualization via the canonical HB‐EGF and COX‐2 pathways.

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Section: Discussionmentioning

confidence: 99%

Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways

et al. 2017

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“…Reduced PG synthesis in the human endometrium may lead to poor endometrial receptivity for embryo implantation since PG synthesis appears to be disrupted in women with repeated IVF failure (Achache et al 2010). It was demonstrated that inhibition of PG synthesis causes pregnancy failure before the implantation process in animals with different types of placentation, beginning from non-invasive placenta in the pig (Kraeling et al 1985) and in ruminants (Erdem & Guzeloglu 2010, Dorniak et al 2011 to invasive placenta in rodents (reviewed in Kennedy et al (2007)).…”

Section: Role Of Pgs During Pregnancy Establishmentmentioning

confidence: 99%

“…Among them, LPAR3 is considered to be an uterine receptivity marker critical for embryo migration and spacing in mice (Ye et al 2005). In women displaying recurrent implantation failure expression of LPAR3 is decreased (Achache et al 2010). In the pig, endometrial LPAR3 expression is upregulated during early pregnancy with the highest levels on days 11-12 .…”

Section: Uterine Receptivity Markers Involved In Pg Synthesismentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F 2a (PGF 2a ) and E 2 (PGE 2 ) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE 2 . Conceptus PGE 2 could be amplified by PGE 2 feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon g and interferon d, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

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“…-интерлейкина-1, -6, -11 (IL-I, -6, -11) [45,46]; -лейкемияингибирующего фактора (LIF) [47]; -сосудисто-эндотелиального фактора роста (VEGF) [48]; -гепаринсвязывающего эпидермального фак-тора роста (ГС-ЭФР) [49]; -матриксных металлопротеиназ (ММР) и их тканевых ингибиторов (ТIMP) [50]; -интегринов [46,47]; -селектинов [51,52]; -гликоделина A [53]; -кадгеринов [45]; -муцинов [45]; -простагландинов [54]; -белка Ki-67 [55,56]. Перечисленные молекулярные маркеры могут определяться в крови, секрете эндометрия или в са-мой ткани эндометрия, полученной при его биопсии.…”

Section: проблемы репродукции 5 2016unclassified

Modern approaches to endometrial receptivity assessment (a review)

Krasnopolskaya¹,

Nazarenko²,

Ershova³

2016

Probl. reprod.

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Согласно существующим представлениям, все причины безуспешности попыток ЭКО, в которых удается выполнить перенос полученных in vitro эм-брионов, могут быть связаны либо с их неспособно-стью к внутриматочной нидации (эмбриональный фактор), либо со снижением рецептивности эндоме-трия (эндометриальный фактор) [1,2]. Необходи-мость совершенствования эндометриального факто-ра программ ЭКО определяется тем, что при исполь-зовании морфологически хороших эмбрионов, по-лученных при оплодотворении донорских ооцитов в программах ЭКО-ОД, только ненамного повышает частоту успешных имплантаций в сравнении со стандартным ЭКО (где качество переносимых эм-брионов может быть не столь хорошим). Это можно видеть из отчета РАРЧ за 2013 г. (опубликован в 2015 г.), согласно которому частота наступления бе-ременности на перенос эмбрионов (ЧНБ пэ ) в про-грамме ЭКО-ОД превысила лишь на 5,3% аналогич-ный показатель в стандартной программе ЭКО (43,8% против 38,5%) [3]. Данный факт указывает на то, что резерв для дальнейшего повышения эффек-

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Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization

Cited by 124 publications

References 33 publications

Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways

Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Modern approaches to endometrial receptivity assessment (a review)

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Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization

Cited by 124 publications

References 33 publications

Autotaxin–lysophosphatidic acid– LPA 3 signaling at the embryo‐epithelial boundary controls decidualization pathways

Autotaxin–lysophosphatidic acid– LPA 3 signaling at the embryo‐epithelial boundary controls decidualization pathways

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Modern approaches to endometrial receptivity assessment (a review)

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Product

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Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways

Autotaxin–lysophosphatidic acid– LPA ₃ signaling at the embryo‐epithelial boundary controls decidualization pathways