Are defects in meiosis genes involved in recurrent pregnancy loss rather than in male infertility?

Objectives
Our primary aim was to gain more insight into maturation arrest of spermatogenesis (MA), and its
relationship with mutations in genes essential for meiosis. Yet, we also investigated the possibility that mutations in human meiosis genes are causing a milder phenotype than predicted from mouse studies.
We speculated that in such cases meiosis could potentially be completed with the production of mature
germ cells but with abnormal chromosomal constitution. After fertilization, miscarriages might be a
consequence.

Methods
Patients with MA (n=40) or couples with recurrent miscarriages (n=23) were analyzed for the presence
of mutations in three genes (SYCP3, MSH4 and DNMT3L) by PCR and sequencing.

Results
Among patients with MA, five changes were observed that also predict an alteration at the amino acid
level. However, since all changes were also present in men with normozoospermia in equal frequencies,
these changes are likely single nucleotide polymorphisms.
Among the 46 patients with recurrent miscarriages, two additional changes were detected that predict
an alteration at the amino acid level. One change was also detected in controls. However, the second
heterozygous change detected in a conserved functional domain of the SYCP3 gene (p.I183T ) was
absent in >200 controls.

Conclusions
Despite our small patient group, these preliminary results confirm our prediction that abnormalities in
meiosis genes might be involved in the formation of gametes with abnormal chromosomal constitution.
Yet, further research is necessary to determine the impact and frequency of such changes before
implementing mutation screening in genetic counseling.