Endocrine Abstracts

Background: Kisspeptins (KISS1) and their receptor, KISS-1R, are expressed at higher levels in first trimester placental trophoblast cells than in term gestation. Expression is localised to the trophoblast compartment. In contrast to KISS1 which is only expressed in the villous trophoblast, KISS-1R is also found in the extravillous trophoblast population. Kisspeptins produced by first trimester trophoblast cells inhibited migration. Pre-eclampsia is known to be caused due to deficient extravillous trophoblast invasion.

Aims: To compare the expression levels of and the allele frequency of known mutations in KISS1 (GPR54) and KISS1R in placenta in normal term pregnancy and pre-eclampsia.

Methods: Following ethical committee approval and informed patient consent placental tissue was obtained at term following elective Caesarean section from women with normal pregnancy (n=25; mean gestational age[standard deviation] 38.5 [2.5] weeks) or pre-eclampsia (n=25; 36.4 [3.4] weeks). Three biopsies of tissue were taken one being formalin fixed and processed to produce paraffin sections for immunohistochemistry. The remaining two biopsies were immediately snap-frozen for subsequent RNA and DNA extraction. Quantitative real time PCR (qRT-PCR) using gene specific primers with SYBR green and immunohistochemistry were used to determine expression of both KISS1 and KISS1R. The frequency of known mutations in KISS1 (rs1132478 and rs4951315) and KISS1R (ss14700521, rs10407968 and rs350132) was assessed using conventional Sanger sequencing.

Results: Both immunohistochemistry and qRT-PCR identified decreased expression of KISS1 and increased expression of KISS1R in pre-eclampsia compare to normal term pregnancy. DNA sequencing confirmed the presence of all known mutations assessed but revealed no alteration in allele frequencies between normal pregnancy and pre-eclampsia.

Discusstion: This study is the first to show altered expression of KISS1 and KISS1R in pre-eclampsia. Further functional studies are warranted to investigate the effect of these alterations in expression on placental development.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.