Modulation of uterine function by endocrine and paracrine factors in ruminants

Uterine adenogenesis in the neonate is critical as uterine glands are essential for pregnancy in adult ruminants. The uterus is stimulated by estrogens (E2) and progesterone (P4) that prepare it to respond to biochemical signals from the conceptus (embryo/fetus and placenta). Interferon tau (IFNT) is responsible for pregnancy recognition and modification of uterine gene expression including sensitivity to placental lactogen and placental growth hormone that stimulate development and gene expression by epithelial cells of uterine glands. P4 is permissive for most actions of IFNT. Novel genes are expressed by uterine luminal and superficial glandular epithelia in response to P4 and IFNT as those cells are in direct contact with conceptus trophectoderm. But, uterine glandular epithelium and stromal cells respond to P4 and IFNT by expressing classical interferon stimulated genes. Uterine receptivity to implantation requires loss of expression of receptors for P4 and E2 by uterine epithelia. P4 stimulates P4 receptor-positive stromal cells to express fibroblast growth factor 10 (FGF10) and hepatocyte growth factor (HGF) that act via their respective receptors on uterine epithelia and trophectoderm to regulate cellular functions and gene expression. FGF10 and IFNT are hypothesized to activate complementary cell signaling pathways that modulate expression of genes for implantation, modify phenotype of uterine stromal cells, silence expression of genes for P4 and E2 receptors, signal pregnancy recognition, suppress genes for immune recognition, alter membrane permeability to enhance conceptus-maternal exchange of factors, increase endometrial vascularity, and activate genes for transport of nutrients into the uterine lumen. Those actions are essential for a successful outcome of pregnancy.