No evidence of association of MUC-1 genetic polymorphism with embryo implantation failure

Abstract

Pregnancy loss can be caused by several factors involved in human reproduction. Although up to 50% of cases remain unexplained, it has been postulated that the major cause of failed pregnancy is an error of embryo implantation. Transmembrane mucin-1 (MUC-1) is a glycoprotein expressed on the endometrial cell surface which acts as a barrier to implantation. The gene that codes for this molecule is composed of a polymorphic tandem repeat of 60 nucleotides. Our objective was to determine if MUC-1 genetic polymorphism is associated with implantation failure in patients with a history of recurrent abortion. The study was conducted on 10 women aged 25 to 35 years with no history of successful pregnancy and with a diagnosis of infertility. The control group consisted of 32 patients aged 25 to 35 years who had delivered at least two full-term live children and who had no history of abortions or fetal losses. MUC-1 amplicons were obtained by PCR and observed on agarose and polyacrylamide gel after electrophoresis. Statistical analysis showed no significant difference in the number of MUC-1 variable number of tandem repeats between these groups (P > 0.05). Our results suggest that there is no effect of the polymorphic MUC-1 sequence on the implantation failure. However, the data do not exclude MUC-1 relevance during embryo implantation. The process is related to several associated factors such as the mechanisms of gene expression in the uterus, specific MUC-1 post-translational modifications and appropriate interactions with other molecules during embryo implantation.

Histidine-rich glycoprotein polymorphism and pregnancy outcome: a pilot study

“…Gene polymorphism for oestrogen receptors (Altmae et al, 2007;Ayvaz et al, 2009), leukaemia inhibitory factor (Kralickova et al, 2005), an enzyme involved in folate metabolism (methylenetetrahydrofolate reductase) (Altmae et al, 2010) and interleukin-1 receptor antagonist (Gremlich et al, 2008) have all been associated with infertility and IVF treatment results. A transmembrane mucin-1 polymorphism has also been suggested to affect implantation (Horne et al, 2001) but further studies have not substantiated these results (Dentillo et al, 2007). Korpelainen et al (1998) showed that male mice with the 165 isoform for vascular endothelial growth factor were infertile, and Huminiecki et al (2001) found male mice with the 121 isoform for vascular endothelial growth factor were subfertile and the litters showed a skewed sex ratio.…”

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“…Alterations in the internal structure of MUC-1 Variable Number of Tandem Repeats (VNTR) have the potential to impact the quantity of core protein O-glycosylation sites, thereby affecting the immunogenicity of the molecule and potentially contributing to pregnancy loss [90]. However, the studies done by Dentillo et al suggested that the number of VNTR repeats in MUC-1 is not linked to implantation failure in women experiencing recurrent abortion [9].…”

“…Moreover, Fleming et al added that, "apart from endogenous factors (such as genetic mutations) that could be detrimental for pregnancy development, various environmental insults (nutrition, pollution and endocrine disruptors, infections stress) have been identified as factors that may affect gamete quality and fertilization, journey of the early embryo through the oviduct, cellular interactions between endometrium and hatched blastocyst or conceptus, foeto-placental development and parturition" [8]. Since 80% of pregnancies end in miscarriage in the first trimester, it has been hypothesized that an error in embryo implantation is the main reason for failed pregnancies [9].…”

Polymorphism of miRNA and its Impact on IVF Failure

“…IVF has since then undergone many modifications and advancements and in 2014 it was reported that more than 5 million babies had been born with the aid of IVF (Kovacs, 2014), however like most other procedures it is yet to be perfected and the success rates are still relatively low. In humans, about 40% of unsuccessful IVF treatments are due to implantation failure (Dentillo et al, 2007), this failure can be related to the embryo transfer technique, embryo quality and endometrial receptivity (O'Flynn, 2014), the latter two are regulated by a cascade of events including miRNAs effect on different genes (Kropp andKhatib, 2015, Shi et al, 2017). There are approximately 240 Single nucleotide polymorphisms (SNP) and rare mutations have been reported in miRNAs and their association with IVF outcome has been established (Kroliczewski et al, 2018, Cho et al, 2016.The appearance of a SNP in a miRNA´s mature sequence may have different but certain consequences on the miRNA either by loss of binding, change in the binding efficacy or recognizing different mRNA targets than their own (Brennecke et al, 2005, Agarwal et al, 2015.…”