Low-Dose Aspirin and Uterine Natural Killer Cells in Mice at Day Seven of Pregnancy

Abstract

Background: Inhibiting the effect of aspirin on prostaglandin results in corpus luteum maintenance in pregnant mice. Uterine natural killer (uNK) cells activate between 5 -7 days of pregnancy. uNK cell differentiation is indirectly regulated by ovarian hormones. Immune cells have important roles in the endometrium at early pregnancy stages. Although low-dose aspirin is effective on ovarian hormones, the effect of low-dose aspirin on the uNK cell population at early pregnancy stages is unknown. Objectives: The aim of this study was to assess the effect of low-dose aspirin on uNK cells at day seven of pregnancy. Materials and Methods: Adult female mice were coupled and divided into two groups (control and experimental). Thereafter, mice in the experimental group received 7.5 mg/kg aspirin twice a day for one week. Blood samples were collected for the measurement of the level of ovarian hormones at day seven of pregnancy and finally the animals were sacrificed by cervical dislocation and uterine horns were removed for histological study. Periodic acid-schiff (PAS) staining was performed for uNK cell counting. Data analysis was conducted by SPSS software. Results: The ovarian hormones level showed a significant difference between the experimental and control groups (P < 0.05). Furthermore, the uNK cell population showed a significant difference between the two groups (P < 0.05). Conclusions: Increased ovarian hormones due to low-dose aspirin administration resulted in decline in the uNK cells number, which may be effective in successful pregnancy.

Controversies on Preeclampsia through the lens of Reproductive Immunology: A Systematic Review

“…Some authors such as Han et al and Beigi et al are of the conviction that anti-inflammatory treatments and anticoagulation treatments are good to use [21,22]. Whereas the utter conviction the other authors like Groeneveld et al [23] is that such treatments are not effective for pregnancy complications like preeclampsia.…”

A Review on Controversies about the Role of Immune and Inflammatory Systems in Implantation Process and Durability of Pregnancy

“…As described by Murphy et al in a high quality review (49), IFN-gamma (secreted mainly by NKs) plays a key in processes such as initiation of vascular remodeling of endometrium, angiogenesis in implantation site and even maintenance of the maternal part of placenta. But in spite of this, inhibition of IFN-gamma secondary to inhibition of NKs is the main reasoning of low dose aspirin administration defenders (43). Conversely, IFN-gamma level were lower in women with 20th-25th week pre-term delivery (49).…”

“…in better interface between embryo and maternal tissue as Boroujeni et al announced (43). On the hypothesis of Haapsamo et al (44), administration of low dose aspirin can improve vascular remodeling; but it's to be noted that inhibition of immune system is somehow throwing the body out with bath water; as a valid paper in Journal of Reproductive Immunology in 2015 announced that uNKs can help durability and remodeling of uterine arteries (45).…”

“…Of course even Gizzo's protocol was not responsive and for this reason in our previous letter we suggested the administration merely at ovulation period (38). Thanks to the up-regulatory effects of aspirin on ovary and ovarian hormones (43). But because of histopathology sequels of ovulation stimulation (47,48) it is still controversial.…”