Immunological mechanisms to establish embryo tolerance in early bovine pregnancy

Abstract

A well-balanced immunological interaction between mother and the semi-allogenic embryo is of particular importance. The objective of the present study was to analyse mechanisms of immune tolerance in bovine pregnancy during peri-implantation. Simmental heifers inseminated with either cryopreserved spermatozoa or seminal plasma were killed 12, 15 or 18 days after oestrus. Uteri were flushed for the recovery of conceptuses and the ipsilateral intercaruncular endometrium was sampled for gene expression analysis. Indoleamine 2,3-dioxygenase (IDO) mRNA, coding for the initial enzyme of the kynurenine pathway, was 18-fold (P < 0.001) more abundant in the endometrium of Day 18 pregnant v. non-pregnant animals. Tandem mass spectrometry revealed a decrease of endometrial l-tryptophan (P = 0.0008), but an increase of l-kynurenine concentration (P = 0.005) from Day 12 to Day 18, suggesting increasing IDO activity (P < 0.03). An in vitro coculture model of endometrial cells showed an induction of IDO expression following interferon-τ exposure primarily in stroma cells, which was confirmed by in situ hybridisation localising IDO mRNA mainly in deep stroma cells. Immunohistochemical analysis revealed fewer CD45-positive leucocytes in the zona basalis of pregnant animals. Elevated IDO activity may reduce the presence of leucocytes in the pregnant endometrium, providing a possible mechanism for protecting the semi-allogenic conceptus from maternal rejection.

Multiple-embryo transfer for studying very early maternal–embryo interactions in cattle

“…Whereas the presence of multiple embryos decreased TNF and increased IL1B protein levels, TNF and IL1B gene expression did not change, which is consistent with data found on day 7 in single-embryo vs cyclic animals (Mansouri-Attia et al 2012, Oliveira et al 2013). In addition, we found that the presence of embryos in the uterus reduces the number of endometrial CD45 positive leukocytes, specifically in caruncular areas; this concurs with previous work carried out by Groebner et al (2011), although their study involved a more advanced development stage and the presence of a single embryo in the uterus. We have also demonstrated that total uterine fluid protein decreases with the number of live embryos recovered, which fits in with a type 4 validation (Muñ oz et al 2012).…”

“…Each gene is capable of producing heterogeneous protein molecules that can be further modified after translation (Katz-Jaffe & Gardner 2007). In fact, on days 12-13, although protein levels in uterine fluid or endometrial tissue may vary, embryo-induced changes in endometrial mRNA are scarce or nonexistent when only a single embryo is present (Forde et al 2011, Groebner et al 2011.…”

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

“…In bovine endometrium, mRNA expression in cells located around blood vessels also suggests expression in immune cells. In a recent study, a strong increase in IDO1 expression was observed in cultured bovine endometrial stromal and glandular epithelial cells after treatment with IFNT [67]. The lower increase in IDO1 mRNA observed on D15 and D18 of pregnancy compared to the IFNA2 treatment could be due to fine-tuned regulation of the maternal immune system during early pregnancy.…”

Differential expression and regulation of Tdo2 during mouse decidualization

“…In mammals, most of tryptophan was metabolized along the kynurenine pathway and tryptophan metabolism was closely correlated with pregnancy (Stone & Darlington 2002, Schröcksnadel et al 2006. During pregnancy, decreased tryptophan concentration and increased concentrations of kynurenines were observed in human plasma and in the uteri of mice and cows (Minatogawa et al 2003, Schröcksnadel et al 2006, Groebner et al 2011. Previous studies have found that tryptophan metabolism was mainly dependent on tryptophan 2,3-dioxygenase (Tdo2) and indoleamine 2,3-dioxygenase (Ido) (Stone & Darlington 2002).…”