Lymphocytic foci in the endometrium of pregnant dairy cows: Characterization and association with reduced placental weight and embryonic loss

Lymphocytic foci (also known as lymphoid aggregates or tertiary lymphoid structures) form within the bovine endometrium after antigenic challenge. Their presence in the pregnant uterus provides evidence for a chronic inflammatory condition perhaps arising from an early postpartum uterine infection. The chronic inflammation that includes the foci could explain greater embryonic loss in dairy cows with early postpartum uterine disease. The objectives were to characterize the size and location of the foci in the pregnant uterus, determine their composition using immunohistochemistry, and associate their presence with the development of the pregnancy and embryonic loss. Pregnant cows (n = 43) were slaughtered on days 28, 35, or 42 of pregnancy. Uterine tissue was collected and processed for histologic and immunohistochemical analysis. The number of small (<100 micron diameter), intermediate (100–250 micron diameter), and large (>250 micron diameter) foci was counted. The number of cows averaging 0, 0.1 to 1, 1.1 to 2, and more than 2 foci per section (small, intermediate, and large; combined) was 7 (16%), 14 (33%), 11 (26%), and 11 (26%), respectively. The average number of small and intermediate foci found in the histologic sections was greater in cows with evidence of uterine infection postpartum (P < 0.05). Lymphocytic foci were distributed within the caruncle and the intercaruncular tissue and comprised a core of CD3-positive cells (T cells) surrounding CD79-positive cells (B cells). The number of lymphocytic foci was correlated with a total inflammation score (on the basis of the total number of inflammatory cells in the endometrium; r2 = 0.49; P < 0.001) and a fibrosis score (based on the extent of fibrosis in the endometrium; r2 = 0.33; P < 0.001). Cows with a high foci count (averaging more than 0.5 foci per section) had lesser (P < 0.01) placental weight on Day 42 of pregnancy. There was no effect of foci count on placental weight on Day 28 or 35. Two cows with embryonic loss were in the highest quartile for foci count. In conclusion, cows with chronic inflammation as evidenced by a large number of lymphocytic foci had reduced placental weight during pregnancy. The number of foci in pregnant cows was associated with early postpartum uterine disease. Whether the foci themselves are inhibitory to pregnancy development or are associated with other bacteriological, morphological, or biochemical changes to the uterus that lead to infertility will need to be investigated.