Natural killer cell reduction induces uteroplacental vasculopathy and fetal growth restriction in wild type rats

Aim: Uterine natural killer cells (uNK cells) are the most abundant leucocytes in pregnant uterus. They are important for placentation and pregnancy maintenance in early and midgestation. We aimed at evaluating their influence on late pregnancy outcome. We reduced the number of NK cells during pregnancy and analyzed fetal parameters at the end of pregnancy. Materials and methods: Pregnant wild type Sprague Dawley rats (n = 6) received 0.5 ml anti asialo GM1 on day 5 and 10 of pregnancy intraperitoneally to reduce NK cell number. Control rats (n = 5) received 0.5 ml rabbit serum on the same days of pregnancy. Fetal weights were measured and uteroplacental units were examined histologically at the end of pregnancy (gestational day 21). Results: After NK cell reduction, fetal weight was significantly lower (mean 4 g vs. 3.6 g in control rats). Moreover, there was maternal vasculopathy in the uterus (mesometrial triangle) in 67% of the dams (4/6). It was characterized by uterine arteries surrounded by fibrosis and (dead) cells without nucleus. In these vessels, there were hardly any endovascular trophoblast cells. One mother rat had 10 miscarried fetuses and one highly growth restricted fetus with a body weight of 1.6 g after NK cell reduction. In this dam, the vasculopathy was very excessive and covering hugh areas of the uters. We found no uterine vasculopathy in the pregnant control rats (0/5). Conclusion: Fetal growth restriction is associated with uterine maternal vasculopathy in rats. Uterine natural killer cells might act as protectors of uterine vessels during pregnancy.