Implantation, Pregnancy and Parturition
(W579) FETAL PROGRAMMING: ADVANCED PLACENTOME DIFFERENTIATION IN TESTOSTERONE-TREATED SHEEP IS FACILITATED BY ANDROGENIC ACTIONS OF TESTOSTERONE.
Astapova, Olga1, Steckler, Teresa1, Lee, Theresa1, Jackson, Leslie1, Padmanabhan, Vasantha1, 1 University of Michigan, Ann Arbor, MI
ABSTRACT- Nutrient exchange between mother and fetus during pregnancy in sheep is facilitated via placentomes, which progressively differentiate to increase the efficiency of exchange as the fetus grows. This is accomplished by a continuous increase in the ratio of fetal to maternal surface area on the placentome as it progresses from type A to B, C, and D. Exposure to steroids during pregnancy has deleterious effects on fetal development. We have found that testosterone (T) treatment during days 30 - 90 of pregnancy causes intrauterine growth retardation, and that placentome differentiation is advanced in the mothers as a possible compensatory mechanism. The objectives of the present study were (a) to confirm the effect of T-treatment on placentome development, and (b) to determine whether it is due to androgenic activity of T. Placentome number, weight and type distribution were determined in control (C), T- and dihydrotestosterone (DHT, a non-aromatizable androgen)-treated (100 mg, im, twice weekly, days 30 to 90 of pregnancy) sheep on day 90 of pregnancy (n=7 C, n=8 T, n=15 DHT). T-treated sheep had an increased number (C: 1.4±0.8, T: 10±3; p=0.004) and weight (C: 13±9 g, T: 107±29 g; p=0.02) of type C placentomes. DHT-treated sheep had an increased number (C: 3±2, DHT: 12±4; p=0.047) and a tendency for an increased weight (C: 30±20 g, DHT: 118±40 g; p=0.06) of type C placentomes. Placentome number and weight distribution did not differ between T- and DHT- treated groups. Visually, placentomes of DHT-treated sheep were similar to those of the T-treated group, with increased vasculature of the capillaries compared to controls. Placental efficiency, calculated as the ratio of fetal to total placentome weight, was similar in all groups. Our findings suggest that placentome differentiation is accelerated in T-treated sheep at day 90 of pregnancy, and this effect is due to the androgenic action of T. Advanced placentome differentiation may be a means to reduce the fetal growth retardation induced by T treatment by maintaining placental efficiency at the normal level. Supported by NIH-HD 41098 & P01 HD 44232.
KEY WORDS: pregnancy, IUGR, placenta