Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland–derived vascular endothelial growth factor and prokineticin receptor polymorphisms

PPARγ controls pregnancy outcome through activation of EG-VEGF: new insights into the mechanism of placental development

“…These proteins have been reported to control multiple biological processes (5,7,29), although the processes that EG-VEGF controls are related mainly to the success of pregnancy (6 -8, 23). Importantly, recent data reported that the levels of circulating EG-VEGF were correlated to the quality of embryonic cohorts used in assisted reproductive technologies as well as to the rates of successful pregnancies (8,31,44). Hence, one can speculate that the failure in placental development observed in the PPAR␥ Ϫ/Ϫ mice might well have occurred during the first stages of placental development.…”

A Common Variant of PROK1 (V67I) Acts as a Genetic Modifier in Early Human Pregnancy through Down-Regulation of Gene Expression

“…We analyzed the coding regions of PROK1 using the Sanger sequence in 142 RPL women and 149 normal controls in a previous report [ 17 ]. The allele and genotype frequencies of PROK1-V67I variant (c.199 G>A, rs7514102) and wild-type (WT) showed no significant differences between RPL and control groups, and the pooled data are 51%, 21% and 28% for GG, GA, and AA genotypes.…”

“…We recently reported the PROK1 variant (V67I) act as a genetic modifier in human early pregnancy [ 17 ]. Previous studies of recurrent pregnancy loss (RPL) showed that women carrying PROKR1 and PROKR2 variants (I379V and V331M) have less susceptibilities for RPL risk, and that trophoblastic cell function alternation by enhancing cell invasiveness may provide the protection from recurrent abortion [ 17 , 18 ]. In contrast, the protection effect of the PROKR1/2 variant may be attenuated if the woman also carries PROK1-V67I [ 17 ].…”

“…Previous studies of recurrent pregnancy loss (RPL) showed that women carrying PROKR1 and PROKR2 variants (I379V and V331M) have less susceptibilities for RPL risk, and that trophoblastic cell function alternation by enhancing cell invasiveness may provide the protection from recurrent abortion [ 17 , 18 ]. In contrast, the protection effect of the PROKR1/2 variant may be attenuated if the woman also carries PROK1-V67I [ 17 ]. Although genetic association research showed evidence of these effects, the underlying mechanism of the common variant of PROK1 (V67I) with regard to modifying RPL risk remains unclear.…”

Updates on Endothelial Functions of Proangiogenic Prokineticin

“…57,58 Indeed, polymorphisms in the prokineticin-1, PKR1, and PKR2 genes are associated with repeated miscarriage. 59 Circulating prokineticin-1 level in pregnant women is higher during the first trimester than during the second and third trimesters. Prokineticin-1 may be a new noninvasive predictive marker of successful embryo implantation for conventional in vitro fertilization-embryo transfer.…”