Abstract
BACKGROUND
Endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. It may lead to infertility and non-specific symptoms such as ...chronic pelvic pain. Endometriosis screening and diagnosis are difficult and time-consuming. Late diagnosis (with a delay ranging from 3.3 to 10.7 years) is a major problem and may contribute to disease progression and a worse response to treatment once initiated. Efficient screening tests might reduce this diagnostic delay. As endometriosis is presumed to be a complex disease with several genetic and non-genetic pathogenic factors, many researchers have sought to identify polymorphisms that predispose to this condition.
OBJECTIVE AND RATIONALE
We performed a systematic review and meta-analysis of the most regularly reported polymorphisms in order to identify those that might predispose to endometriosis and might thus be of value in screening.
SEARCH METHODS
The MEDLINE database was searched for English-language publications on DNA polymorphisms in endometriosis, with no date restriction. The PubTator text mining tool was used to extract gene names from the selected publications’ abstracts. We only selected polymorphisms reported by at least three studies, having applied strict inclusion and exclusion criteria to their control populations. No stratification based on ethnicity was performed. All steps were carried out according to PRISMA guidelines.
OUTCOMES
The initial selection of 395 publications cited 242 different genes. Sixty-two genes (corresponding to 265 different polymorphisms) were cited at least in three publications. After the application of our other selection criteria (an original case-control study of endometriosis, a reported association between endometriosis and at least one polymorphism, data on women of reproductive age and a diagnosis of endometriosis in the cases established by surgery and/or MRI and confirmed by histology), 28 polymorphisms were eligible for meta-analysis. Only five of the 28 polymorphisms were found to be significantly associated with endometriosis: interferon gamma (IFNG) (CA) repeat, glutathione S-transferase mu 1 (GSTM1) null genotype, glutathione S-transferase pi 1 (GSTP1) rs1695 and wingless-type MMTV integration site family member 4 (WNT4) rs16826658 and rs2235529. Six others showed a significant trend towards an association: progesterone receptor (PGR) PROGINS, interCellular adhesion molecule 1 (ICAM1) rs1799969, aryl-hydrocarbon receptor repressor (AHRR) rs2292596, cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) rs743572, CYP2C19 rs4244285 and peroxisome proliferator-activated receptor gamma (PPARG) rs1801282), and 12 showed a significant trend towards the lack of an association: tumor necrosis factor (TNF) rs1799964, interleukin 6 (IL6) rs1800796, transforming growth factor beta 1 (TGFB1) rs1800469, estrogen receptor 1 (ESR1) rs2234693, PGR rs10895068, FSH receptor (FSHR) rs6166, ICAM1 rs5498, CYP1A1 rs4646903, CYP19A1 rs10046, tumor protein 53 (TP53) rs1042522, X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) rs25487 and serpin peptidase inhibitor clade E member 1 (SERPINE1) rs1799889; however, for the 18 polymorphisms identified in the latter two groups, further studies of the potential association with the endometriosis risk are needed. The remaining five of the 28 polymorphisms were not associated with endometriosis: glutathione S-transferase theta 1 (GSTT1) null genotype, vascular endothelial growth factor alpha (VEGFA) rs699947, rs833061, rs2010963 and rs3025039.
WIDER IMPLICATIONS
By carefully taking account of how the control populations were defined, we identified polymorphisms that might be candidates for use in endometriosis screening and polymorphisms not associated with endometriosis. This might constitute the first step towards identifying polymorphism combinations that predispose to endometriosis (IFNG (CA) repeat, GSTM1 null genotype, GSTP1 rs1695, WNT4 rs16826658 and WNT4 rs2235529) in a large cohort of patients with well-defined inclusion criteria. In turn, these results might improve the diagnosis of endometriosis in primary care. Lastly, our present findings may enable a better understanding of endometriosis and improve the management of patients with this disease.
Abstract
Context
Maternal obesity has a significant impact on placental development. However, this impact on the placenta’s structure and function (ie, nutrient transport and hormone and cytokine ...production) is a controversial subject.
Objective
We hypothesized that maternal obesity is associated with morphologic, secretory, and nutrient-related changes and elevated levels of inflammation in the placenta.
Design
We collected samples of placental tissue from 2 well-defined groups of pregnant women from 2017 to 2019. We compared the 2 groups regarding placental cytokine and hormone secretion, immune cell content, morphology, and placental nutrient transporter expressions.
Setting
Placenta were collected after caesarean section performed by experienced clinicians at Centre Hospitalier Intercommunal (CHI) of Poissy-Saint-Germain-en-Laye.
Patients
The main inclusion criteria were an age between 27 and 37 years old, no complications of pregnancy, and a first-trimester body mass index of 18–25 kg/m2 for the nonobese (control) group and 30–40 kg/m2 for the obese group.
Results
In contrast to our starting hypothesis, we observed that maternal obesity was associated with (1) lower placental IL-6 expression and macrophage/leukocyte infiltration, (2) lower placental expression of GLUT1 and SNAT1-2, (3) a lower placental vessel density, and (4) lower levels of placental leptin and human chorionic gonadotropin production.
Conclusion
These results suggest that the placenta is a plastic organ and could optimize fetal growth. A better understanding of placental adaptation is required because these changes may partly determine the fetal outcome in cases of maternal obesity.
Down syndrome (DS) is the most common genetic disease at birth; on average, it affects 1 in 700 newborns. The syndrome features cognitive impairment, susceptibility to certain diseases, and (in some ...cases) congenital malformations. Improvements in medical care for people with DS have led to an increase in life expectancy. Furthermore, the systematic provision of specific support during childhood improves cognitive function and autonomy in adulthood. Consequently, patients and their families are now seeking the same rights as healthy people. Access to procreation is an emerging debate. The presumption of infertility in DS is based on a few old studies. Down syndrome appears to cause spermatogenesis defects in men and premature menopause in women. When assisted reproductive technology makes it possible to solve these problems, the question of fertility in DS must be addressed. Without entering into highly controversial ethical considerations related to parenthood for people with DS, we reviewed the literature on fertility in DS and tried to specify the associated genetic risk.
This article presents a new class of distances between arbitrary nonnegative Radon measures inspired by optimal transport. These distances are defined by two equivalent alternative formulations: (i) ...a dynamic formulation defining the distance as a geodesic distance over the space of measures (ii) a static “Kantorovich” formulation where the distance is the minimum of an optimization problem over pairs of couplings describing the transfer (transport, creation and destruction) of mass between two measures. Both formulations are convex optimization problems, and the ability to switch from one to the other depending on the targeted application is a crucial property of our models. Of particular interest is the Wasserstein–Fisher–Rao metric recently introduced independently by 7,15. Defined initially through a dynamic formulation, it belongs to this class of metrics and hence automatically benefits from a static Kantorovich formulation.
Maternal obesity is increasingly prevalent and is associated with elevated morbidity and mortality rates in both mothers and children. At the interface between the mother and the fetus, the placenta ...mediates the impact of the maternal environment on fetal development. Most of the literature presents data on the effects of maternal obesity on placental functions and does not exclude potentially confounding factors such as metabolic diseases (e.g., gestational diabetes). In this context, the focus of this review mainly lies on the impact of maternal obesity (in the absence of gestational diabetes) on (i) endocrine function, (ii) morphological characteristics, (iii) nutrient exchanges and metabolism, (iv) inflammatory/immune status, (v) oxidative stress, and (vi) transcriptome. Moreover, some of those placental changes in response to maternal obesity could be supported by fetal sex. A better understanding of sex-specific placental responses to maternal obesity seems to be crucial for improving pregnancy outcomes and the health of mothers and children.
After birth, the lungs must resorb the fluid they contain. This process involves multiple actors such as surfactant, aquaporins and ENaC channels. Preterm newborns often exhibit respiratory distress ...syndrome due to surfactant deficiency, and transitory tachypnea caused by a delay in lung liquid resorption. Our hypothesis is that surfactant, ENaC and aquaporins are involved in respiratory transition to extrauterine life and altered by preterm birth. We compared these candidates in preterm and term fetal sheeps.
We performed cesarean sections in 8 time-dated pregnant ewes (4 at 100 days and 4 at 140 days of gestation, corresponding to 24 and 36 weeks of gestation in humans), and obtained 13 fetal sheeps in each group. We studied surfactant synthesis (SP-A, SP-B, SP-C), lung liquid resorption (ENaC, aquaporins) and corticosteroid regulation (glucocorticoid receptor, mineralocorticoid receptor and 11-betaHSD2) at mRNA and protein levels.
The mRNA expression level of SFTPA, SFTPB and SFTPC was higher in the term group. These results were confirmed at the protein level for SP-B on Western Blot analysis and for SP-A, SP-B and SP-C on immunohistochemical analysis. Regarding aquaporins, ENaC and receptors, mRNA expression levels for AQP1, AQP3, AQP5, ENaCα, ENaCβ, ENaCγ and 11βHSD2 mRNA were also higher in the term group.
Expression of surfactant proteins, aquaporins and ENaC increases between 100 and 140 days of gestation in an ovine model. Further exploring these pathways and their hormonal regulation could highlight some new explanations in the pathophysiology of neonatal respiratory diseases.
To measure mitochondrial content and the expression of estrogen-related receptor-γ (ERRγ, a major inducer of mitochondrial biogenesis) in placentas from women with intrauterine growth restriction ...(IUGR) associated or not with pre-eclampsia (PE), relative to control placentas.
Case-control study.
Teaching hospital and university research laboratory.
Thirty-nine placentas from women with IUGR, 8 IUGR+PE, and 30 controls.
None.
Mitochondrial DNA and protein content, gene and protein expression.
We observed significantly lower placental mitochondrial DNA and protein contents (associated with down-regulation of ERRγ expression) in IUGR and IUGR+PE placentas, relative to control placentas. Our results also revealed that the placental mitochondrial DNA content was directly correlated with fetal weight. Moreover, we observed significantly lower peroxisome proliferator-activated receptor-γ coactivator-1α and sirtuin 1 messenger RNA expression levels in IUGR+PE placentas, relative to control placentas.
The low mitochondrial DNA and protein contents observed in IUGR placentas are probably due to down-regulation of ERRγ expression. This finding suggests that ERRγ has a major role in the control of placental development.
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