Carryover effects of maternal late-gestation heat stress on granddaughters' growth and mammary gland development.

Maternal (F) exposure to late-gestation heat stress reduces their daughter's (F) mammary gland fat pad (FP) mass, parenchyma (PAR) mass, and epithelial cell proliferation when evaluated at birth and weaning, and the daughters go on to produce less milk in their first lactation. Herein, we investigated the effect of maternal late-gestation heat stress on whole-body growth and mammary development of their granddaughters (F). Multiparous F cows had access to heat abatement (n = 41, shade, and active cooling via fans and water soakers) or not (n = 41, shade only) for the last 56 d of gestation during a subtropical summer. Consequently, the F daughters, born to F cows, were heat-stressed (HT, n = 36) or cooled (CL, n = 37) in utero during the last 2 mo of gestation. All F heifers were raised as an identically managed cohort until first calving. The F granddaughters, born to HT (HT, n = 12) or CL (CL, n = 17), were raised as an identically managed cohort until 70 d of age. Dry matter intake, BW, hip height, wither height, chest girth, head circumference, mammary gland teat length, and left-right and front-rear teat distances were measured. Average daily gain was calculated for the preweaning period (0-49 d). Mammary ultrasounds were performed on d 21, 49, and 70 (n = 9/group) on the rear left and right quarters to quantify PAR and FP areas. Mammary biopsies were collected for histological evaluation of epithelial structures (hematoxylin and eosin staining), and to quantify cells positive for estrogen receptor, α subunit (ERα), cell proliferation (Ki67), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling, TUNEL). Heifer growth from birth to d 49 was similar between CL and HT for all parameters evaluated. Distances between teats and teat length were not different between groups. On d 70, CL heifers tended to have a greater average PAR (right and left quarters) relative to HT heifers. Although the left FP was smaller in HT heifers relative to CL heifers, the average FP was not different. The lumenal and nonlumenal epithelial structures in the PAR of HT heifers were significantly smaller than those of CL heifers. In addition, HT heifers had a reduced percentage of proliferating cells in the epithelial and stromal compartments and a greater percentage of apoptotic cells, particularly in the stroma. The percentage of ERα positive cells was significantly reduced in HT heifers. In summary, although HT heifers' DMI was similar and they grew at the same rate as CL heifers throughout the preweaning phase, their mammary glands had smaller PAR areas with fewer epithelial structures characterized by reduced cell turnover and lower ERα expression. These early changes in the microstructure and cellular turnover of the mammary gland may partly explain the reduction in lactation performance relative to CL counterparts at maturity.