Instability at Microsatellite Sequences in Spontaneously Aborted Human Embryos Provides Evidence for a Novel Mechanism for Recurrent Miscarriages

Abstract

Abstract. Several factors have been proposed to confer a risk for abortion of the embryo. However, the aetiology of spontaneous abortions remains unclear. In the present study we investigated if an increased mutational rate occurs in the embryonic tissue and whether this phenomenon is associated with recurrent miscarriage. The mutational rate was assessed in 30 spontaneously aborted embryos using a bank of 8 highly polymorphic microsatellite markers, each one located on a different chromosome. The microsatellite sequences of DNA extracted from distal sites of each embryo were amplified by the polymerase chain reaction and the electrophoretic patterns were compared. Shifts in the mobility of the microsatellites indicating instability were scored for 12 among 30 (40%) specimens, thus suggesting that microsatellite instability (MI) is a relatively common feature of spontaneously aborted embryonic tissues. Association was found between instability and the absence of normal childbirth: 11 among 18 cases without a normal childbirth exhibited evidence of MI while only one among 12 cases with normal childbirth was positive for MI. Our results suggest that instability at microsatellite sequences which indicate decreased fidelity in DNA replication and repair are associated with the recurrent abortion of the embryo, particularly in cases without a normal childbirth.

Microsatellite instability in patients with chronic obstructive pulmonary disease

“…In addition, recent studies suggested that MI is also a detectable phenomenon in spontaneously aborted embryonic tissues (17)(18)(19). MI is the direct result of decreased accuracy in DNA repair and replication and it reflects an elevated mutational rate which indicates destabilization in the genome.…”

Detection of Herpes simplex Virus (HSV) in Aborted Material Using the Polymerase Chain Reaction Technique

“…Several factors have been implicated: chromosomal and genomic alterations [1][2][3][4], anatomical defects of the uterus [5][6], endocrinological and immunological disorders [7][8][9], as well as bacteria and virus infections such as rubella and herpes viruses [10,11]. At present there are probably more than 100 different herpes viruses.…”

Genomic instability and the link to infertility: A focus on microsatellites and genomic instability syndromes

“…In samples that came from a normal birth, only 8% (1 of 12 cases) had MSI. THRA1 and D6S344 presented instability in 5 of the cases whilst D7S531 did not present MSI [152]. Both THRA1 and D6S344 have been found to be highly polymorphic microsatellite markers in other studies [157][158][159][160].…”

“…In this section we have discussed MSI occurrences in infertile patients independent of genomic instability syndromes. After searching the literature, we found four papers [152][153][154][155], that reported links between MSI and infertility/RM, independent of genomic instability syndromes. We have identified that from these four studies that MSI may be a common feature in idiopathic infertility.…”