Developmental programming in sheep: administration of testosterone during 60-90 days of pregnancy reduces breeding success and pregnancy outcome.
Evidence suggests that exposure to excess steroids during critical periods of fetal development leads to reproductive disorders. Exposure of female lambs to excess testosterone (T) from Days 60 to 90 of gestation (T60-90; term, 147 days) delayed onset of the LH surge and resulted in to male-typical reproductive behavior. The objectives of this study were to test the ability of T60-90 ewes to mate, conceive and lamb during the first three breeding seasons (Years 1, 2 and 3). Pregnant Suffolk ewes were injected with T propionate in cottonseed oil (100mg, im twice weekly) or vehicle (control; C) from Days 60 to 90 of gestation. In Year 1, ewes (C=12, T60-90=12) were kept with a vasectomized ram for 3 months and markings/visual observation of copulations were recorded. Rams had paint applied to their chest to facilitate detection of estrus and mating. All C but only three T60-90 ewes were marked (P<0.001). All ewes were then estrus-synchronized with two injections of prostaglandin F2alpha (20mg, im) given 11 days apart and allowed to mate with a painted, fertile ram. Nine of 12 C and 4 of 12 T60-90 ewes (P=0.1) were mated. Based on estrus and long-term monitoring of progesterone, more C than T60-90 became pregnant (82 and 18%, respectively; P<0.01). In Year 2, to maximize ram exposure, two C and two T60-90 estrus-synchronized ewes were placed with a painted, fertile ram at a time and mated ewes were removed to a nearby pen to force mating with others. Twenty-four hour video monitoring revealed the rams mated more C than T60-90 ewes (83 and 25%, respectively; P=0.01). In both Years 1 and 2, the rams preferred C over T60-90 ewes; therefore in Year 3 rams were given access only to T60-90 ewes. Only four T60-90 estrus-synchronized ewes were placed with a painted ram at a time. Not given an option, 91% of the T60-90 ewes were marked resulting in 4 of 11 (36%; first-service pregnancy rate in the breeding herd was 91%) ewes becoming pregnant to the synchronized estrus. Collectively these studies showed that fertility in T60-90 females was severely compromised, even after overcoming ram preference for controls.