Genetic polymorphisms of serotonin transporter and receptor 1A could influence success during embryo implantation and maintenance of pregnancy

Palomares, Arturo Reyes; Ramírez, Ana María Lendínez; Pérez-Nevot, Beatriz; Cortés-Rodríguez, Miriam; Martínez, Francisco Martínez; Garrido, Nicolás; Ruiz-Galdón, Maximiliano; Reyes‐Engel, Armando

doi:10.1016/j.fertnstert.2013.02.026

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…To date, more than 20 reports have described a variety of genetic variants associated or not with the risk of recurrent implantation failure (RIF) in patients undergoing IVF, comparing alleles frequencies between patients with RIF and control group (Table S1). These risk factors include single nucleotide polymorphisms (SNPs) in the genes for tumour suppressor protein 53 [10]–[12], follicle-stimulating hormone receptor (FSHR) [13], [14], methylenetetrahydrofolate reductase (MTHFR) [15]–[17], human leukocyte antigen-G (HLA-G) [18], [19], vascular endothelial growth factor (VEGF) [20], [21], plasminogen activator inhibitor-1 (PAI) [20], progesterone receptor (PR) [22], [23], and cyclooxygenase-2 (COX-2) [24], serotonin transporter (SERT) and serotonin receptor 1A (5-HT1A) [25]. Moreover, it was recently suggested that the implantation process depends on combinations of several genetic and environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs

et al. 2014

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BackgroundA multiple pregnancy is now considered to be the most common adverse outcome associated with in vitro fertilization (IVF). As a consequence, the identification of women with the best chances of embryo implantation is a challenge in IVF program, in which the objective is to offer elective single-embryo transfer (eSET) without decreasing the pregnancy rate. To date, a range of hormonal and clinical parameters have been used to optimize eSET but none have significant predictive value. This variability could be due to genetic predispositions related to single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the embryo implantation rate for patients undergoing intracytoplasmic sperm injection program (ICSI).Materials and MethodsA 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(−397T>C), BMP15(−9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(−725C>G), VEGF(+405G>C), TNFα(−308A>G), AMHR(−482A>G), PAI-1(4G/5G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the total patients population (n = 428) and a subgroup with homogeneous characteristics (n = 112).ResultsOnly the VEGF(+405G>C) and TNFα(−308A>G) polymorphisms impacted fertilization, embryo implantation and pregnancy rates. Moreover, the combined VEGF+405.GG and TNFα-308.AG or AA genotype occurred significantly more frequently in women with high implantation potential. In contrast, the VEGF+405.CC and TNFα-308.GG combination was associated with a low implantation rate.ConclusionWe identified associations between VEGF(+405G>C) and TNFα(−308A>G) polymorphisms (when considered singly or as combinations) and the embryo implantation rate. These associations may be predictive of embryo implantation and could help to define populations in which elective single-embryo transfer should be recommended (or, conversely, ruled out). However, the mechanism underlying the function of these polymorphisms in embryo implantation remains to be determined and the associations observed here must be confirmed in a larger, more heterogeneous cohort.

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Section: Introductionmentioning

confidence: 99%

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs

et al. 2014

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“…The LC variant haplotype was also associated with a lower pregnancy rate. 30 These findings underscore the negative role of the serotonin genetic variant on the decidual receptiveness, thus affecting the very early phases of embryo implantation and pregnancy establishment. Maternal supply of 5-HT has been reported to be critical to early pregnancy establishment.…”

Section: Discussionmentioning

confidence: 89%

Polymorphic variants of the serotonin receptor, 5-HT1A, and the serotonin transporter, 5-HTTLPR, and adverse pregnancy outcomes: A pilot study

Taube

Tevet

Altarescu

et al. 2015

Journal of Reproductive Health and Medicine

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“…Serotonin transport in pregnancy is a delicate balance; patients undergoing assisted reproduction who carry the LL genotype for 5-HTTLPR in the serotonin transporter promoter, which results in increased levels of SERT, had lower clinical pregnancy rates and increased rates of biochemical pregnancy loss ( Palomares et al, 2013 ). Prenatal exposure to bisphenol A increases hippocampal SERT in a murine model ( Matsuda et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Gestational Age Variation in Human Placental Drug Transporters

et al. 2022

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Patient and providers’ fear of fetal exposure to medications may lead to discontinuation of treatment, disease relapse, and maternal morbidity. Placental drug transporters play a critical role in fetal exposure through active transport but the majority of data are limited to the 3rd trimester, when the majority of organogenesis has already occurred. Our objective was to define gestational age (GA) dependent changes in protein activity, expression and modifications of five major placental drug transporters: SERT, P-gp, NET, BCRP and MRP3. Apical brush border membrane fractions were prepared from fresh 1st, 2nd and 3rd trimester human placentas collected following elective pregnancy termination or planned cesarean delivery. A structured maternal questionnaire was used to identify maternal drug use and exclude exposed subjects. Changes in placental transporter activity and expression relative to housekeeping proteins were quantified. There was evidence for strong developmental regulation of SERT, NET, P-gp, BCRP and MRP3. P-gp and BCRP decreased with gestation (r = −0.72, p < 0.001 and r = −0.77, p < 0.001, respectively). Total SERT increased with gestation but this increase was due to a decrease in SERT cleavage products across trimesters. Uncleaved SERT increased with GA (r = 0.89, p < 0.001) while cleaved SERT decreased with GA (r = −0.94, p < 0.001). Apical membrane NET overall did not appear to be developmentally regulated (r = −0.08, p = 0.53). Two forms of MRP3 were identified; the 50 kD form did not change across GA; the 160 kD form was steady in the 1st and 2nd trimester and increased in the 3rd trimester (r = 0.24, p = 0.02). The 50 kD form was expressed at higher levels. The observed patterns of SERT, NET P-gp, BCRP and MRP3 expression and activity may be associated with transporter activity or decreased placental permeability in the 1st trimester to transporter specific substrates including commonly used psychoactive medications such as anti-depressants, anti-psychotics, and amphetamines, while transport of nutrients and serotonin is important in the 1st trimester. Overall these observations are consistent with a strong protective effect during organogenesis. 3rd trimester estimates of fetal exposure obtained from cord blood likely significantly overestimate early fetal exposure to these medications at any fixed maternal dose.

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Genetic polymorphisms of serotonin transporter and receptor 1A could influence success during embryo implantation and maintenance of pregnancy

Cited by 5 publications

References 35 publications

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs

Polymorphic variants of the serotonin receptor, 5-HT1A, and the serotonin transporter, 5-HTTLPR, and adverse pregnancy outcomes: A pilot study

Gestational Age Variation in Human Placental Drug Transporters

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