Recent advancements in Explainable Artificial Intelligence (XAI) aim to bridge the gap between complex artificial intelligence (AI) models and human understanding, fostering trust and usability in AI systems. However, challenges persist in comprehensively interpreting these models, hindering their widespread adoption. This study addresses these challenges by exploring recently emerging techniques in XAI. The primary problem addressed is the lack of transparency and interpretability in AI models to humanity for institution-wide use, which undermines user trust and inhibits their integration into critical decision-making processes. Through an in-depth review, this study identifies the objectives of enhancing the interpretability of AI models and improving human understanding of their decision-making processes. Various methodological approaches, including post-hoc explanations, model transparency methods, and interactive visualization techniques, are investigated to elucidate AI model behaviours. We further present techniques and methods to make AI models more interpretable and understandable to humans including their strengths and weaknesses to demonstrate promising advancements in model interpretability, facilitating better comprehension of complex AI systems by humans. In addition, we provide the application of XAI in local use cases. Challenges, solutions, and open research directions were highlighted to clarify these compelling XAI utilization challenges. The implications of this research are profound, as enhanced interpretability fosters trust in AI systems across diverse applications, from healthcare to finance. By empowering users to understand and scrutinize AI decisions, these techniques pave the way for more responsible and accountable AI deployment.

This study combined in vitro production of bovine blastocysts, multiple embryo transfer techniques, and a conceptus-endometrial explant co-culture system to test the hypothesis that bovine endometrium exposed to long vs. short day 15 conceptuses would exhibit a different transcriptome profile reflective of potential for successful pregnancy establishment. Bovine endometrial explants collected at the late luteal stage of the estrous cycle were cultured in RPMI medium for 6 h with nothing (control), 100 ng/mL recombinant ovine interferon tau (IFNT), a long day 15 conceptus, or a short day 15 conceptus. Transcriptional profiling of the endometrial explants found that exposure of endometrium to IFNT, long conceptuses, or short conceptuses altered (P < 0.05) expression of 491, 498, and 230 transcripts, respectively, compared to the control. Further analysis revealed three categories of differentially expressed genes (DEG): (i) commonly responsive to exposure to IFNT and conceptuses, irrespective of size (n = 223); (ii) commonly responsive to IFNT and long conceptuses only (n = 168); and genes induced by the presence of a conceptus but independent of IFNT (n = 108). Of those 108 genes, 101 were exclusively induced by long conceptuses and functional analysis revealed that regulation of molecular function, magnesium-ion transmembrane transport, and clathrin coat assembly were the principal gene ontologies associated with these DEG. In conclusion, bovine endometrium responds differently to age-matched conceptuses of varying size in both an IFNT-dependent and -independent manner, which may be reflective of the likelihood of successful pregnancy establishment.

Embryonic or fetal loss in cattle is associated with problems that occur during oocyte maturation, early embryonic development, conceptus elongation, maternal recognition of pregnancy (MRP), and/or placental attachment and implantation. Many of these problems manifest as inadequate or asynchronous communication between the developing conceptus and endometrium, resulting in pregnancy failure. This review will provide an overview of how various conceptus-endometrial paracrine signaling systems control the fate of early pregnancy in cattle and other ruminants. We begin by summarizing the actions of interferon-tau, the classic MRP signal in ruminates, and then explore how other secretory factors derived from either the conceptus or endometrium influence establishment and maintenance of pregnancy. Insight into how the endometrium responds to male vs. female conceptuses or conceptuses produced by in vitro methods will also be described. Specific focus will be placed on describing how “omic” technologies and other cutting-edge techniques have assisted with identifying novel conceptus and/or endometrial factors and their functions. Recent findings indicate that the endometrial transcriptome and histotroph are altered by conceptus sex, quality, and origin, suggesting that the endometrium is a sensor of conceptus biochemistry. Although the endometrium has a certain level of flexibility in terms of conceptus-maternal interactions, this interplay is not sufficient to retain some pregnancies. However, new information inspires us to learn more and will help develop technologies that mitigate early embryonic loss and reproductive failure in ruminants and other animals.

Bovine endometrium consists of epithelial and stromal cells that respond to conceptus interferon tau (IFNT), the maternal recognition of pregnancy (MRP) signal, by increasing expression of IFN-stimulated genes (ISGs). Endometrial epithelial and stromal cell specific ISGs are largely unknown but hypothesized to have essential functions during pregnancy establishment. Bovine endometrial epithelial cells were cultured in inserts above stromal fibroblast (SF) cells for 6 h in medium alone or with IFNT. The epithelial and SF transcriptomic response was analyzed separately using RNA sequencing and compared to a list of 369 DEGs recently identified in intact bovine endometrium in response to elongating bovine conceptuses and IFNT. Bovine endometrial epithelial and SF shared 223 and 70 DEGs in common with the list of 369 endometrial DEGs. Well known ISGs identified in the epithelial and SF were ISG15, MX1, MX2, and OAS2. DEGs identified in the epithelial but not SF included a number of IRF molecules (IRF1, IRF2, IRF3 and IRF8), mitochondria SLC transporters (SLC25A19, SLC25A28 and SLC25A30), and a ghrelin receptor (GHSR). Expression of ZC3HAV1, an anti-retroviral gene, increased specifically within the SF. Gene ontology analysis identified the type I IFN signaling pathway and activation of nuclear factor kappa B transcription factors as biological processes associated with the epithelial cell DEGs. This study has identified biologically relevant IFNT stimulated genes within specific endometrial cell types. The findings provide critical information regarding the effects of conceptus IFNT on specific endometrial compartments during early developmental processes in cattle.

Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic cluster of differentiation 11c (CD11c) positive dendritic cells, increased anti-inflammatory interleukin (IL)-10, and activation of forkhead box P3 (FOXP3) positive regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-conceptus immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3, and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7, and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10, and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3⁺ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

: In brief: Standard in vitro produced (IVP) bovine embryo culture media limit embryonic development. Culturing IVP bovine embryos in standard IVP bovine embryo culture media conditioned with oviduct and/or endometrial cells improves blastocyst formation and reduces the time to formation. In vitro embryo production in cattle greatly impacts blastomere biochemistry, embryo rate of development and pre- and post-transfer survival. In vivo, the bovine embryo migrates through the oviduct isthmus before entering the uterus on approximately day 4 of development where it remains unattached within the uterine lumen until day 20 of gestation. During this time, the embryo is sequentially exposed to oviduct followed by endometrial secretions that support embryonic development. Considering this, we tested the effect of culturing in vitro produced (IVP) bovine embryos sequentially in oviduct epithelial- (OEp; days 1–3) followed by endometrial epithelial- (EEp) or EEp and fibroblast cell (EEp/F; days 4–8)-conditioned media on embryonic development using a time-lapse monitoring system. Compared to control, culturing IVP embryos in EEp- or EEp/F-conditioned media without prior culture in OEp-conditioned media increased blastocyst formation (P < 0.05) and reduced the time to blastocyst formation (P < 0.05). Culturing IVP bovine embryos in OEp-conditioned media followed by EEp- or EEp/F-conditioned media, however, had the greatest impact on embryo developmental kinetics and increased morula and blastocyst formation (P < 0.05) and reduced time to formation (P < 0.05). Day 8 blastocyst cell numbers, diameter and quality were not significantly different, although, blastocyst quality scores were less (indicative of better quality) for all cell-conditioned media compared to control. In conclusion, IVP bovine embryo development may be improved using a sequential embryo culture system involving bovine oviduct followed by endometrial cell-conditioned media.