The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles

Matorras, Roberto; Martínez‐Arranz, Ibon; Arretxe, Enara; Iruarrizaga‐Lejarreta, Marta; Corral, Blanca; Ibáñez-Pérez, Jone; Expósito, Antonia; Prieto, Begoña; Elortza, Félix; Alonso, Cristina

doi:10.1007/s10815-019-01670-z

Cited by 20 publications

(6 citation statements)

References 51 publications

(74 reference statements)

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“…Although the topic is highly current, only five publications were found in the systematic literature search that met all our inclusion criteria. Several former studies investigated the role of lipids in oocytes [ 66 , 67 ], early stages of embryo development [ 52 , 56 , 58 , 66 , 68 , 69 , 70 , 71 ], placenta in late pregnancy [ 72 , 73 ], as well as endometrial tissues during the window of implantation [ 74 ], and in endometrial fluid [ 75 ]. However, in these studies, lipid composition was mostly investigated with MS and not with MSI.…”

Section: Discussionmentioning

confidence: 99%

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Gitta

Márk

Szentpéteri

et al. 2023

Life

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Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents, but they also play a role in lipid signaling. Previous studies have suggested an important role of lipids in implantation; therefore, our aim was to investigate the lipid changes during this period based on the available literature. The systematic literature search was performed on Ovid MEDLINE, Cochrane Library, Embase, and LILACS. We included studies about lipid changes in the early embryonal stage of healthy mammalian development published as mass spectrometry imaging. The search retrieved 917 articles without duplicates, and five articles were included in the narrative synthesis of the results. Two articles found a different spatial distribution of lipids in the early bovine embryo and receptive uterus. Three articles investigated lipids in mice in the peri-implantation period and found a different spatial distribution of several glycerophospholipids in both embryonic and maternal tissues. Although only five studies from three different research groups were included in this systematic review, it is clear that the spatial distribution of lipids is diverse in different tissues and their distribution varies from day to day. This may be a key factor in successful implantation, but further studies are needed to elucidate the exact mechanism.

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Section: Discussionmentioning

confidence: 99%

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Gitta

Márk

Szentpéteri

et al. 2023

Life

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“…These discrepancies could be due to the different analyzed specimens (serum versus endometrial biopsy). Some evidence also manifests that LA has negative effects on oocyte maturation ( 33 ), which could be mediated by the role of lipids in the physical properties and biological functions of membranes ( 13 ). Other authors measured the LA : ALA ratio (n-6 to n-3) and they found that women with higher LA : ALA ratios had greater embryo implantation and pregnancy rates compared to women with reduced LA : ALA ratios ( 42 , 43 ), suggesting a potential role for increased LA to enhance endometrial inflammation and receptivity ( 43 ) and for elevated ALA to disturb embryo implantation ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

“…The first endometrial metabolome studies have analyzed women with endometriosis and have suggested several potential biomarkers of the disease ( 10 – 12 ). The whole metabolome profiling in the uterus of fertile and infertile women undergoing assisted reproductive techniques showed that specific metabolomic signatures contribute to beneficial endometrial microenvironment to achieve pregnancy ( 13 – 15 ). These are the first findings indicating that metabolomics is a powerful tool in unravelling uterine health and understanding receptive-phase endometrial functions to achieve successful embryo implantation.…”

Section: Introductionmentioning

confidence: 99%

Endometrial whole metabolome profile at the receptive phase: influence of Mediterranean Diet and infertility

et al. 2023

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IntroductionSeveral metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD.MethodsThe study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC–MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD. ResultsWe provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus. ConclusionThe study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.

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“…embryo development and subsequent implantation in the uterus. In this process, LE cells have to go through sequential changes during early pregnancy, e.g., proliferation and differentiation (Aplin and Ruane, 2017), cytoskeleton remodeling (Tung et al, 1988;Kalam et al, 2018), vesicle trafficking (Li et al, 2020;Rai et al, 2021), secretion and resorption of uterine fluid contents (Azkargorta et al, 2018;Exposito et al, 2018;Matorras et al, 2020), etc., to reach into a receptive state that supports embryo implantation. All these LE changes are energy-consuming processes, which undoubtedly depend on glucose uptake and metabolism.…”

Section: Discussionmentioning

confidence: 99%

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

et al. 2021

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GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1–4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epithelium in vivo or in vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs) in vitro or in vivo. In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA). In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανβ3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.

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The lipidome of endometrial fluid differs between implantative and non-implantative IVF cycles

Cited by 20 publications

References 51 publications

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review

Endometrial whole metabolome profile at the receptive phase: influence of Mediterranean Diet and infertility

GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation

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