Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a “jelly-roll” fold, carbohydrate-recognition domain and sugar-binding preference resembling other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ, suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low concentrations in first trimester maternal sera are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure due to vasodilatation in pregnant animals suggest its therapeutic potential in preeclampsia.

Objective: To investigate the predictive value of the combination of first‐trimester serum placental protein 13 (PP13), uterine artery Doppler pulsatility index (PI) and pulse wave analysis (augmentation index at a heart rate of 75 beats per min (AIx‐75)), and to evaluate concurrent and contingent strategies using this combination for assessing the risk of pre‐eclampsia in high‐risk women.Methods: In this nested case–control study, serum PP13, uterine artery mean PI and AIx‐75 were measured at between 11 + 0 and 13 + 6 weeks' gestation in women at increased risk of pre‐eclampsia. For each case of pre‐eclampsia (n = 42), five matched controls were randomly selected from the study group. Gestation specific multiples of the median (MoMs) were adjusted for body mass index, ethnicity, smoking, age and parity. MoMs were compared between cases and controls using the Wilcoxon rank sum test. Sensitivities and specificities were derived from receiver–operating characteristics curves.Results: Compared with controls, women who developed pre‐eclampsia had lower PP13, higher uterine artery mean PI and higher AIx‐75 (P < 0.001). For a 10% false‐positive rate, the best detection rate for pre‐eclampsia (85.7% (95% CI, 71.5–94.6%)) and pre‐eclampsia requiring delivery before 34 weeks (92.9% (95% CI, 66.1–99.8%)) was achieved by concurrent testing with all three markers. The best contingency screening sequences for pre‐eclampsia were (AIx‐75 → PP13 → mean PI) and (PP13 → AIx‐75 → mean PI), with an 86% detection rate for false‐positive rates of 9 and 10%, respectively. These two sequences would require 410 and 414 tests, respectively, compared with 756 tests in concurrent testing.Conclusion: Combination of first‐trimester PP13, uterine artery mean PI and pulse‐wave analysis is promising for the prediction of pre‐eclampsia in women at increased @ a‐priori risk and may be useful in clinical practice. Contingency screening achieved similar detection rates to concurrent testing, but required almost 50% fewer tests, making it a more cost‐effective option. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Galectins regulate cell growth, proliferation, differentiation, apoptosis, signal transduction, mRNA splicing, and interactions with the extracellular matrix. Here we focus on the galectins in the reproductive system, particularly on a group of six galectins that first appears in anthropoid primates in conjunction with the evolution of highly invasive placentation and long gestation. Of these six, placental protein 13 (PP13, galectin 13) interacts with glycoproteins and glycolipids to enable successful pregnancy. PP13 is related to the development of a major obstetric syndrome, preeclampsia, a life-threatening complication of pregnancy which affects ten million pregnant women globally. Preeclampsia is characterized by hypertension, proteinuria, and organ failure, and is often accompanied by fetal loss and major newborn disabilities. PP13 facilitates the expansion of uterine arteries and veins during pregnancy in an endothelial cell-dependent manner, via the eNOS and prostaglandin signaling pathways. PP13 acts through its carbohydrate recognition domain that binds to sugar residues of extracellular and connective tissue molecules, thus inducing structural stabilization of vessel expansion. Further, decidual PP13 aggregates may serve as a decoy that induces white blood cell apoptosis, contributing to the mother’s immune tolerance to pregnancy. Lower first trimester PP13 level is one of the biomarkers to predict the subsequent risk to develop preeclampsia, while its molecular mutations/polymorphisms that are associated with reduced PP13 expression are accompanied by higher rates of preeclampsia We propose a targeted PP13 replenishing therapy to fight preeclampsia in carriers of these mutations.