Interferon tau-dependent and independent effects of the bovine conceptus on the endometrial transcriptome†

Abstract

This study investigated bovine conceptus-induced modifications to the endometrial transcriptome related to effects of interferon tau (IFNT), conceptus origin (in vivo vs. in vitro) and conceptus sex. In vitro (IVF) or in vivo (superovulation and artificial insemination, AI) produced blastocysts were transferred into recipient heifers on Day 7 of the estrous cycle. On Day 15, IVF- or AI-derived conceptuses were obtained by uterine flushing and individually placed on endometrial explants in media for 6 h. Explants were also cultured with media alone as a control or media containing 100 ng/mL IFNT. Total explant RNA was analyzed by RNA-Seq. Incubation of endometrium with IFNT or IVF- or AI-derived conceptuses changed (P ≤ 0.001) expression of 491, 498 and 576 transcripts, respectively, compared to the control. Further, 369 differentially expressed genes (DEGs) were common between explants exposed to IFNT or a conceptus. 240 DEGs were uniquely altered by conceptuses (IVF- and AI-derived) but not IFNT. Of these transcripts, 46 were shared between the IVF and AI groups, while 61 and 133 were specific to IVF and AI conceptuses, respectively. Five genes (MLPH, PROM2, MYADM, VN1R4L, HTR1A) were more abundant in endometrium exposed to female compared to male conceptuses (P < 0.001). A single gene (ARL4C) was more abundant in response to male conceptuses (P < 0.001) than female conceptuses. These data support the hypothesis that conceptus regulation of gene expression in the endometrium is complex and involves factors other than IFNT that may have a biological role in pregnancy establishment.

Aspects of embryo-maternal communication in establishment of pregnancy in cattle

“…Comparison of this list of differentially expressed genes (DEG) with the common list of genes altered in endometrial explants following culture with 100 ng/ml IFNT or a Day 15 conceptus (from Sánchez et al, 2019b; Fig. 1) indicated that all of the DEG induced in the endometrium by blastocyst-stage embryos are IFNT-stimulated, in contrast to Day 15 when a significant number of IFNT-independent genes are induced (Mathew et al, 2019;Sánchez et al, 2019bsee below).…”

“…This difference is reflected in the fact that in commercial embryo transfer, the majority of in vitro-produced blastocysts are transferred fresh while the majority of in vivo-derived blastocysts are transferred frozen (Viana, 2018). Mathew et al (2019) compared the transcriptomic response of the endometrium following exposure to IFNT or a conceptus derived from the transfer of an in vivo-derived (superovulation and AI) or in vitro-produced (IVF) blastocyst in order to identify novel transcripts dependent and independent on IFNT, conceptus origin and conceptus sex. IVF-or AIproduced blastocysts were transferred into recipient heifers on Day 7 of the estrous cycle.…”

“…The aim of this short review is to summarize some of our recent findings in relation to embryo maternal interaction during bovine pregnancy establishment and to put them in the wider context of fertility in cattle. Several of the recent studies referred to below have used an endometrial explant co-culture system to elucidate this fine dialogue by examining changes in endometrial gene expression induced by blastocysts (Passaro et al, 2018 or by an elongating conceptus (Mathew et al, 2019;Bagés-Arnal et al, 2019). Due to the maintenance of normal cellular and extracellular architecture in endometrial explants (Borges et al, 2012), some of the limitations of traditional cell culture can be overcome; for example, uterine explants allow the communication between resident populations of endometrial cells which cannot be achieved with current 2D and 3D cell culture technologies.…”

The role of CAPG in molecular communication between the embryo and the uterine endometrium: Is its function conserved in species with different implantation strategies?

“…Other studies have shown that there are early IFNT-independent changes to the endometrium (Forde, Carter, et al, 2011;Mathew et al, 2019), as well as during the pregnancy recognition period (Bauersachs et al, 2012). Of these transcripts that were identified as conceptus-specific but independent of IFN exposure, we have identified that CAPG modifies 5 of these.…”

Protein Synthesis by Day 16 Bovine Conceptuses during the Time of Maternal Recognition of Pregnancy

“…These interactions are predominantly mediated by the pregnancy recognition signal Interferon Tau (IFNT), a type-I interferon produced by the trophectoderm cells which is required to inhibit luteolysis and maintain the CL. In addition to IFNT, which significantly modifies the transcriptome of the endometrium [17,18], other proteins are produced by the conceptus [19,20] coordinated with increased production of IFNT. Moreover, the response of the endometrium to the conceptus as a whole is greater than its response to prolonged exposure to a type I interferon for 3 days in vivo [12,18].…”