Reprint of: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

Nnoaham, Kelechi E.; Hummelshøj, Lone; Webster, Premila; D’Hooghe, Thomas; Nardone, Fiorenzo De Cicco; Nardone, Carlo de Cicco; Jenkinson, Crispin; Kennedy, Stephen; Zondervan, Krina T.

doi:10.1016/j.fertnstert.2019.08.082

Cited by 43 publications

(43 citation statements)

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“…A typical migraine presents with a recurrent, unilateral and episodic headache of moderate to severe intensity [7]. Both endometriosis and migraine portend substantial morbidity with wide-ranging socioeconomic burdens to sufferers, their families, relationships, and the society at large [8][9][10][11]. Notably, the diagnosis of the two disorders is challenging, due to a lack of diagnostic markers, which often results in missed or delayed diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Adewuyi

Sapkota

Auta

et al. 2020

Genes

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Observational epidemiological studies indicate that endometriosis and migraine co-occur within individuals more than expected by chance. However, the aetiology and biological mechanisms underlying their comorbidity remain unknown. Here we examined the relationship between endometriosis and migraine using genome-wide association study (GWAS) data. Single nucleotide polymorphism (SNP) effect concordance analysis found a significant concordance of SNP risk effects across endometriosis and migraine GWAS. Linkage disequilibrium score regression analysis found a positive and highly significant genetic correlation (rG = 0.38, P = 2.30 × 10−25) between endometriosis and migraine. A meta-analysis of endometriosis and migraine GWAS data did not reveal novel genome-wide significant SNPs, and Mendelian randomisation analysis found no evidence for a causal relationship between the two traits. However, gene-based analyses identified two novel loci for migraine. Also, we found significant enrichment of genes nominally associated (Pgene < 0.05) with both traits (Pbinomial-test = 9.83 × 10−6). Combining gene-based p-values across endometriosis and migraine, three genes, two (TRIM32 and SLC35G6) of which are at novel loci, were genome-wide significant. Genes having Pgene < 0.1 for both endometriosis and migraine (Pbinomial-test = 1.85 ×10−°3) were significantly enriched for biological pathways, including interleukin-1 receptor binding, focal adhesion-PI3K-Akt-mTOR-signaling, MAPK and TNF-α signalling. Our findings further confirm the comorbidity of endometriosis and migraine and indicate a non-causal relationship between the two traits, with shared genetically-controlled biological mechanisms underlying the co-occurrence of the two disorders.

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Section: Introductionmentioning

confidence: 99%

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Adewuyi

Sapkota

Auta

et al. 2020

Genes

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“…Poor pregnancy outcomes are also associated with the disease, including preterm labor, pre-eclampsia, ectopic pregnancy, miscarriage, and intrauterine growth restriction (7). Endometriosis has a significant socioeconomic impact, costing the UK an estimated £8.5 billion pounds each year, with societal cost being mostly attributed to loss of productivity (8,9). Diagnosis from onset of symptoms can take an average of 7-8 years.…”

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confidence: 99%

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

2020

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Endometriosis is a complex, heterogeneous, chronic inflammatory condition impacting ∼176 million women worldwide. It is associated with chronic pelvic pain, infertility, and fatigue, and has a substantial impact on health-related quality of life. Endometriosis is defined by the growth of endometrial-like tissue outside the uterus, typically on the lining of the pelvic cavity and ovaries (known as "lesions"). Macrophages are complex cells at the center of this enigmatic condition; they are critical for the growth, development, vascularization, and innervation of lesions as well as generation of pain symptoms. In health, tissue-resident macrophages are seeded during early embryonic life are vital for development and homeostasis of tissues. In the adult, under inflammatory challenge, monocytes are recruited from the blood and differentiate into macrophages in tissues where they fulfill functions, such as fighting infection and repairing wounds. The interplay between tissue-resident and recruited macrophages is now at the forefront of macrophage research due to their differential roles in inflammatory disorders. In some cancers, tumor-associated macrophages (TAMs) are comprised of tissue-resident macrophages and recruited inflammatory monocytes that differentiate into macrophages within the tumor. These macrophages of different origins play differential roles in disease progression. Herein, we review the complexities of macrophage dynamics in health and disease and explore the paradigm that under disease-modified conditions, macrophages that normally maintain homeostasis become modified such that they promote disease. We also interrogate the evidence to support the existence of multiple phenotypic populations and origins of macrophages in endometriosis and how this could be exploited for therapy.

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“…Endometriosis (EMS) is a chronic inflammatory and estrogen-dependent disorder in which the ectopic endometrium grows outside the uterine locations such as in the ovary or other pelvic tissue and in peritoneal surface; in most cases, this seems to arise by retrograde menstruation [110]. Beyond the classical pelvic pain, EMS is associated with poor quality of life, reduced work productivity, and with a number of clinical repercussions such as affective disorders, metabolic dysfunctions, anxiety, inflammation, cardiovascular diseases, and increased cancer risks [111]. The origin of EMS appears to be related to genetic and environmental factors, but its causality requires additional evidence.…”

Section: The Benefits Of Melatonin In the Treatment Of Endometriosismentioning

confidence: 99%

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Chuffa

Lupi

Cucielo

et al. 2019

IJMS

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The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

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Reprint of: Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

Cited by 43 publications

References 0 publications

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Shared Molecular Genetic Mechanisms Underlie Endometriosis and Migraine Comorbidity

Endometriosis-Associated Macrophages: Origin, Phenotype, and Function

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

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