"Genetic bases of defective chromosome content or structure In a biological sense, genetic defects leading to abortion may originate from two partners: The conceptus and the uterus. From the conceptus side, it is well established that chromosomal anomalies lead to implantation defects. However, they occur mostly stochastically; to be the genetic cause of a recurrent loss, a genetic defect leading to systematic chromosome anomalies has to be found, as nicely reviewed recently by Kurahashi and coworkers. Abnormal chromosome structure may originate from defects in the checkpoint mechanisms that constitute a quality control factory of the cell, which is able to detect meiosis anomalies and is called Spindle Assembly Checkpoint (SAC), constituted by pro teins such as Mad1, Mad2, Bub1, Bub3, BubR1, and Mps1. A very recent study addressed this question on the general issue of defective reproduction performance, by screening two candidate genes, aurora kinase B (AURKB) and synaptonemal complex protein 3 (SYCP3). In the AURKB gene, the authors identified low frequency (0.5%) non synonymous variants (c. 155C.T, c. 236T.C, and c. 880G.A) inducing the changes p.A52V, p.I79T, and p.A294T in the polypeptidic chain, respectively. 236T >C and 880G >A were associated with antecedents of pregnancy losses. This preliminary study is one of those that pave the way toward evaluating genes playing a role in the quality of the meiotic progression. Two other genes have been investigated to this respect in miscarriage, BUB1 and MAD2. The authors showed firstly that as generally assumed, half the embryos from spontaneous miscarriages have an abnormal karyotype. By western blotting, the authors quantified the two proteins and estimated that they were under expressed in pathological cases. The authors also isolated chorionic villi where they targeted BUB1 and MAD2 expression by short hairpin RNA (shRNA) and showed that this induces an abnormal karyotype at a ~ sixfold increased frequency, compared to controls (indicating that mitotic defects can also be induced when these genes are dysfunctional). The role of MAD2 in such defects was independently confirmed by another study on trisomic abortuses. Clearly, therefore, anomalies in spindle assembly can lead to aneuploidies, and infertilities in the most severe cases, such as in the case of the recently identified mutation of the cohesin STAG3, leading to premature ovarian failure, but less severe mutations in the SAC genes could lead to variants that have more subtle effects. There is clearly space for studying this aspect of spindle stability on a wider basis than what has been performed up to now in the context of recurrent miscarriage."