NLRP7 and the Genetics of Hydatidiform Moles: Recent Advances and New Challenges

Abstract

NOD-like receptor proteins (NLRPs) are emerging key players in several inflammatory pathways in Mammals. The first identified gene coding for a protein from this family is Nlrp5 and was originally called Mater for “Maternal Antigen That Mouse Embryos Require” for normal development beyond the two-cell stage. This important discovery was followed by the identification of other NLRPs playing roles in inflammatory disorders and of the first maternal-effect gene in humans, NLRP7, which is responsible for an aberrant form of human pregnancy called hydatidiform mole (HM). In this review, we recapitulate the various aspects of the pathology of HM, highlight recent advances regarding NLRP7 and its role in HM and related forms of reproductive losses, and expand our discussion to other NLRPs with a special emphasis on those with known roles in mammalian reproduction. Our aim is to facilitate the genetic complexity of recurrent fetal loss in humans and encourage interdisciplinary collaborations in the fields of NLRPs and reproductive loss.

The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling

“…Interestingly, the expression of some NLR family members, including NLRP2, -3 and -10, was previously detected at high levels in reproductive organs [48]. Indeed, mutations in the NLR gene NLRP7 has been described as a causative hallmark for recurrent hydatidiform moles (RHM) and reproductive loss [49]. …”

The hydatidiform mole

“…8 In rare cases the PHM have also been reported with other karyotypes (diploid biparental, triploid dyginic, tetraploid triandric). 52 These explanations were reconsidered in 2003 by Golubovsky 53 . He points out that (1) it would need a regular "stock" of anuclear oocytes in order to ensure the frequency of the CHM, (2) the empty oocytes can be obtained "in vitro" but question their viability "in vivo" and/or whether they can be fertilized (3) in the case of twins, of which one is a CHM and the other a fetus, it has been observed that the prevalence of CHM diploids is androgenetic 46XX, 54 which can be explain by diploidization concept and the monozygotic origin of such associations (Fig.…”

La môle hydatiforme complète

“…En fait, de nombreuses combinaisons chromosomiques ont pu être observées. La présence de deux populations cellulaires de caryotype différent a également été rapportée, on parle alors de môle complète mosaïque [13]. Retenons que dans la majorité des cas, ces môles complètes sont d'origine androgénétique.…”

“…Par exemple, l'ovocyte est anucléé avant ou décennies, ces fréquences ont tendance à baisser [13]. La surveillance médicale et la meilleure nutrition de la mère expliquent la diminution de ces pathologies qui restent, dans 80 % des cas, des tumeurs bénignes dans les pays développés.…”