Neonatal exposure to progesterone and estradiol alters uterine morphology and luminal protein content in adult beef heifers

Exposure of the developing urogenital tract to steroids can affect structure and function of adult tissues and compromise reproductive performance. This study was conducted to determine 1) if exposure of neonatal heifer calves to progesterone (P) and estradiol benzoate (E), delivered from a commercial growth-promoting implant, would affect adult uterine morphology or uterine luminal protein content; and 2) whether such effects would be related to neonatal age at the first exposure. At birth (Day 0), 20 crossbred beef heifers were assigned to 1 of 4 treatment groups (n = 6 per group), defined by age at implant placement. Heifers either received an implant on Days 0, 21 or 45, or served as untreated controls. The heifers were maintained together and slaughtered at 15 mo of age, during the luteal phase of an induced estrous cycle, when reproductive tracts and blood samples were obtained. Peripheral plasma P concentrations were determined by RIA Uterocervical wet weights were recorded, and uterine luminal flushings (ULF) were assayed for total protein. Cross-sections of uterine tissues were evaluated histomorphometrically to determine myometrial and endometrial areas and relative endometrial gland density. Treatment did not affect plasma P concentrations (3.2 +/- 0.5 ng/ml). Regardless of age at treatment, neonatal PE exposure reduced uterocervical wet weight by 35% (112.8 < 173.9 +/- 13.9 g, P < 0.01), myometrial area by 23% (125.3 < 162.8 +/- 8.5 mm2; P < 0.02), and endometrial area by 27% (33.3 < 45.4 +/- 2.7 mm2; p < 0.09) compared with the untreated controls. Endometrial gland density was reduced (P < 0.01) by 40% in treated heifers. This effect was related to age at implant placement. Uterine gland density was reduced (P < 0.01) by 65% in heifers treated at birth, while reductions of 22 and 33% were observed for heifers treated on neonatal Day 21 or 45, respectively. Consistently, ULF protein content was lower (P < 0.01) in the treated heifers (2.67 < 4.98 +/- .72 mg/ULF). Thus, exposure of newborn calves to PE can have profound effects on adult uterine morphology and environment, the extent of which may depend upon the developmental period when exposure occurs. The potential of such alterations to affect reproductive performance in adult beef heifers remains to be investigated.