Melatonin fed in early gestation increases fetal weight

Uterine blood flow and placenta size are determinants of the amount of nutrients reaching the attached fetuses within the uterus. Inevitably, selection for prolificacy increases the number of fetuses in utero and, therefore, already limits nutrient exchange between the maternal and fetal circulations. Uterine capacity is considered to be limiting when the number of developing conceptuses exceeds 14 (Dziuk 1968). Consequently, the excessive intrauterine crowding occurring in a proportion of mature prolific sows between d 25 and 40 of gestation leads to limited placental development by d 30, and subsequently to intrauterine growth retardation (IUGR) and reduced birthweight of entire litters (Foxcroft 2012). Melatonin has been used in sheep models to induce umbilical vasodilation and increase the amount of blood flow and nutrients reaching the fetus (Thakor et al. 2010), providing a valuable treatment for pregnancies experiencing IUGR. The aim of this project was to determine whether supplementing diets with melatonin between d 25 and d 50 of pregnancy in gilts would increase fetal growth to d 50 of gestation.

Pre-pubertal gilts (n = 29) were induced to ovulate at 22 weeks of age using a combination of PG600 (Intervet America, Inc., Millsboro, DE, USA) and daily boar exposure. At their induced oestrus, gilts were inseminated twice (24 h apart) using commercial pooled semen doses (80 mL doses of 3 × 10⁻⁹ sperm per dose, ≤4 days old: SABOR Pty Ltd, Clare, SA, Australia). Days 25 to 50 of gestation, gilts were treated with either 5 mL canola oil (CTL), 18 mg melatonin in 5 mL canola oil (MEL18) or 36 mg melatonin in 5 mL canola oil (MEL36). Day 50 of pregnancy, gilts were slaughtered at a commercial abattoir. Reproductive tracts were dissected, and the number of corpora lutea (CL; ovulation rate), number and weight of fetuses, fetal crown–rump length, as well as placental weights were recorded. Statistical analysis was performed using a mixed general linear model (SPSS 24.0, IBM, Armonk, NY, USA) with treatment, replicate, fetal sex and gilt as fixed effects and litter size as a covariate. Data are presented as estimated means ± s.e. from mixed models.

The number of fetuses recovered was not different among treatments (9.82 ± 1.70, 8.34 ± 1.30 and 8.93 ± 1.60, for CTL, MEL18 and MEL36 respectively). Melatonin treatment did not affect CL, fetal and placenta weights combined, placental weights and crown–rump lengths (P > 0.05). Fetuses from the MEL36 group were heavier (P < 0.05) compared to the CTL group (CTL, 65.77 ± 4.78 g; MEL18, 73.42 ± 5.08, MEL36, 81.85 ± 3.80).

The current limited data from an experimental gilt model provides preliminary evidence that oral supplementation with melatonin from early to mid-gestation can increase fetal weight at d 50. Studies with larger numbers, and in situations of more extreme intrauterine crowding and limited placental development, are needed to confirm the benefits of using melatonin to increase litter weights when intrauterine crowding in early gestation is linked to subsequent litter-wide IUGR and low birthweight. Studies that follow the pregnancy to farrowing also need to be conducted to ensure the effects of melatonin on fetal weight are continuing through to birth after treatment ceases at d 50 of gestation.