Placental insufficiency is regarded as the primary factor contributing to late-term abortion and perinatal death of foals. Often when problems associated with late-term pregnancy in the horse are manifest the condition is well-advanced and therapeutic intervention may not be effective in rescuing the pregnancy. If a compromised pregnancy due to placental insufficiency could be identified early, the pregnancy might be sustained through medical intervention. Because the placenta is the sole source of circulating relaxin in the mare, we hypothesized that systemic relaxin may serve as a biomarker of placental function and fetal well-being and a predictor of pregnancy outcome at delivery. To test this hypothesis we monitored plasma relaxin in mares (light breeds) with normal and problematic pregnancies from clinical cases presented to the veterinary hospital and in pregnant mares experimentally inoculated with Streptococcus equi zooepidemicus to induce uterine infection. Upon establishment of placentitis, mares were assigned to different therapeutic strategies and responsiveness was monitored. Blood was collected during the third trimester of pregnancy, and relaxin content was determined using a homologous equine relaxin radioimmunoassay. The results reported here show a positive relationship between low circulating relaxin and poor pregnancy outcome in mares with compromised placental function. While relaxin may have value as a diagnostic assay for identifying mares with high-risk pregnancies associated with placental dysfunction, the variable results obtained from mares undergoing drug treatment for experimentally induced placentitis make it difficult to determine the reliability of relaxin for evaluating therapeutic efficacy.
Consumption of wild-type (toxic) endophyte-infected tall fescue (E+) by horses during late gestation is known to adversely affect pregnancy outcome; however, little is known of the potential disruptive consequences of E+ consumption by mares during the critical phases of placentation and fetal development in early pregnancy. The objective of this study was to evaluate the detrimental effects of feeding E+ to mares during early gestation. Mares (n = 12) paired by stage of gestation (d 65 to 100) were assigned to diets (six per diet) consisting of endophyte-free (E-) or E+ tall fescue seed (50% E- or E+ tall fescue seed, 45% sweet feed, and 10% molasses fed at 1.0% of BW/d). Mares also had ad libitum access to E+ or E- annual ryegrass hay, and were fed diets for 10 d. Following removal from the tall fescue diet on d 11, mares were placed on common bermudagrass pasture and monitored until d 21. Morning and evening rectal temperatures were recorded and daily blood samples were collected for progesterone and prolactin (PRL) analyses, whereas samples for 3,4-dihydroxyphenyl acetic acid (a catecholamine metabolite) analysis were collected on alternate days. For clinical chemistry analysis, blood samples were collected on d 0, 5, 10 and 21. Daily urine samples were collected for ergot alkaloid analysis, and ultrasonography was performed for presence of echogenic material in fetal fluids. Rectal temperatures (E+ 37.76+/-0.03; E- 37.84+/-0.03 degrees C) and serum PRL concentrations (E+ 14.06< or =0.76; E- 12.11+/-0.76 ng/mL) did not differ (P = 0.96) between treatments. Measuring the change in basal serum concentration from d 0 over time, progesterone concentrations did not differ (-0.64 +/-1.49 and -0.55+/-1.47 ng/mL for E+ and E- mares, respectively). There was no negative pregnancy outcome, and ultrasonography indicated no increase in echogenic material in fetal fluids. Plasma 3,4-dihydroxyphenyl acetic acid concentrations decreased (P < 0.05) in E+ compared with E- mares (2.1+/-0.14 and 4.4+/0.43 ng/mL, respectively). Urinary ergot alkaloid concentration was greater (P < 0.01) in mares consuming E+ compared with E- (532.12+/- 52.51 and 13.36+/-2.67 ng/mg of creatinine, respectively). Although no fetal loss was observed during the current study, elevated concentrations of urinary ergot alkaloid were consistent with depressed endogenous catecholamine activity, suggestive of an endocrine disruptive effect of hypothalamic origin.
The objective of the current study was to examine the effects of supplemental melatonin implants on uterine artery blood flow from mid to late gestation in beef cattle and subsequent development of their male offspring. Commercial beef heifers (n = 32) and cows (n = 25) were bred via artificial insemination and assigned to 1 of 2 groups supplemented with melatonin implants (MEL) or without (CON) at day 180, 210, and 240 of gestation. Uterine artery blood flow was determined using color Doppler ultrasonography. A subset of 12 crossbred heifers (n = 6 MEL; n = 6 CON) underwent Cesarean sections on day 243 ± 2 of gestation to allow for placentome collection. Maternal and fetal serum were collected to analyze melatonin concentrations. The remaining cattle were allowed to calve and at weaning (195 ± 2 d of age), bull calves (n = 15) were castrated and testicular tissue harvested for seminiferous tubule analysis. Heifer uterine artery blood flow was increased (P = 0.009) at day 240 of gestation in MEL compared with CON heifers. Cow uterine artery blood flow was increased (P = 0.003) in MEL compared with CON cows irrespective of gestational day. Maternal and fetal concentrations of melatonin were increased (P < 0.05) in MEL compared with CON heifers. The percent of placentome capillary area per mm2 was decreased (P = 0.019) in MEL compared with CON heifers, while cotyledonary ANGPT1 mRNA tended to increase (P = 0.095) in MEL compared with CON heifers. At weaning, body weight of male offspring and their scrotal circumference were increased (P < 0.05) in calves born to MEL compared with CON dams, while seminiferous tubule diameter and area were not different (P > 0.40) between treatments. In summary, melatonin supplementation increased uterine artery blood flow in mid to late gestating cattle, but this was not accompanied by an increase in fetal weight. Alterations in postnatal development of bulls, including increased body weight and scrotal circumference, warrants future investigations related to attainment of puberty and subsequent fertility of offspring born to melatonin supplemented dams.
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