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Intrauterine growth restriction (IUGR) and postnatal catch-up growth confer an increased risk of adult-onset disease. Overnourishment of adolescent ewes generates IUGR in ~50% of lambs, which subsequently exhibit increased fractional growth rates. We investigated putative epigenetic changes underlying this early postnatal phenotype by quantifying gene-specific methylation at cytosine:guanine (CpG) dinucleotides. Hepatic DNA/RNA was extracted from IUGR [eight male (M)/nine female (F)] and normal birth weight (12 M/9 F) lambs. Polymerase chain reaction was performed using primers targeting CpG islands in 10 genes: insulin, growth hormone, insulin-like growth factor (IGF)1, IGF2, H19, insulin receptor, growth hormone receptor, IGF receptors 1 and 2, and the glucocorticoid receptor. Using pyrosequencing, methylation status was determined by quantifying cytosine:thymine ratios at 57 CpG sites. Messenger RNA (mRNA) expression of IGF system genes and plasma IGF1/insulin were determined. DNA methylation was independent of IUGR status but sexual dimorphism in IGF1methylation was evident (MF (both P<0.001). IGF1mRNA expression correlated negatively with IGF1methylation (r=-0.507, P=0.002) and positively with plasma IGF1 (r=0.884, P<0.001). Carcass and empty body weights were greater in males (P=0.002–0.014) and this gender difference in early body conformation was mirrored by sexual dimorphism in hepatic IGF1DNA methylation, mRNA expression and plasma IGF1 concentrations. more...

Nutritional feedback provided by systemic hormones, such as insulin and leptin, influences reproductive neuroendocrine output within the hypothalamus, yet the mechanisms and their interaction with photoperiodic cues remain unresolved in seasonal species. Here, peripheral glucose (G) infusion was used to increase endogenous concentrations of insulin and leptin in food-restricted sheep kept in either long-day (LD) or short-day (SD) photoperiod, and responses were examined in terms of pulsatile luteinising hormone (LH) (gonadotrophin-releasing hormone by inference) output and hypothalamic gene expression for nutritionally sensitive neuropeptides and receptors. We addressed the hypothesis that these hypothalamic responses were correlated and influenced by photoperiod. Oestradiol-implanted, castrated male sheep were kept 16 weeks in SD (8 h light/day) or LD (16 h light/day) and then transferred to the opposite photoperiods for 8 weeks, during which food was restricted to 90% requirement to maintain body weight (maintenance). For the final 6 days, food was reduced to 75% maintenance, and sheep in both photoperiods were infused intravenously with G (60 mM/h) or saline (S) (n=8/group). G-infused sheep had higher mean plasma concentrations of G, insulin and leptin than S-infused sheep, with no effect of photoperiod. In LD, but not in SD, G infusion increased LH pulse frequency and pulse amplitude. In LD, but not in SD, gene expression in the hypothalamic arcuate nucleus was lower in G- than S-infused sheep for neuropeptide Y (NPY) and agouti-related peptide (AGRP) and was higher in G- than S-infused sheep for pro-opiomelanocortin (POMC). Gene expression for leptin and insulin receptors was not affected by photoperiod or infusion. These results are consistent with the involvement of NPY, AGRP and POMC in mediating the reproductive neuroendocrine response to increased systemic nutritional feedback, and they support the hypothesis that hypothalamic responses to nutritional feedback are influenced by photoperiod in sheep. more...

Summary.Lactating (N = 12) and non-lactating (N = 6) red deer hinds and one stag at pasture were given concentrates (500 g/head) containing melatonin (5 mg/head) daily at 16:00 h from 18 June to 16 October. The stag shed the antler velvet and started rutting 5 weeks ahead of untreated stags, and hinds had their first oestrus and ovulation of the breeding season in mid-September, 5 weeks in advance of control lactating (N = 9) and non-lactating (N = 5) hinds. Treated hinds were allowed to mate with the treated stag and control hinds ran in an adjacent paddock with an untreated stag. All hinds became pregnant during the study with all but 2 melatonin-fed hinds (1 lactating, 1 non-lactating) and 1 control hind (lactating) conceiving at the first oestrus.Melatonin-treated hinds lost slightly more live weight than did controls from June to November, but their suckled calves grew throughout at a rate similar to those of control hinds. more...

Summary.From 17 February 1987 (Day 1) to 5 June 1988 (Day 475), 6 red deer hinds which had been in natural daylength (NL/M) and 6 hinds which had been in continuous artificial light for the previous month (CL/M) were each given melatonin (5 mg in feed) daily at 15:00 h. Six controls (C) received unsupplemented feed. From Day 1 all hinds were in natural daylight and ovarian cyclicity was assessed from plasma progesterone concentrations. Group C first went into anoestrus on 15 March 1987 (Day 27 ± 9·2 (s.e.m)), recommenced cyclicity on 23 October (Day 249 ± 2·3) and went into anoestrus again on 2 April 1988 (Day 411 ± 8·7). Group CL/M first went into anoestrus 31 days earlier (P< 0·05) on 12 February (Day –4 ± 7·8), before the start of melatonin treatment; 4 hinds then recommenced ovarian cycles 132 days earlier (P< 0·001) on 13 June (Day 117 ± 5·8) and continued to cycle for a longer period than did controls. Group NL/M hinds were cyclic at the start of melatonin feeding and continued to cycle for 1 year or more (N = 6). Plasma prolactin concentrations remained suppressed (< 20 ng/ml) for the duration of melatonin-feeding (Groups CL/M and NL/M) whereas control values (Group C) were elevated (20–120 ng/ml) between April and August (P< 0·05).The ovarian response by hinds to melatonin therefore depends on initial reproductive status and recent photoperiodic history, and continued administration to cyclic hinds stimulates prolonged ovarian cyclicity irrespective of the time of year.Keywords:red deer; melatonin; progesterone; ovarian cyclicity; out-of-season breeding; prolactin more...

Summary.Concentrations of progesterone in peripheral plasma of red deer hinds were basal ( < 1 ng/ml) during lactation/seasonal anoestrus, but increased abruptly at the onset of the breeding season. Lactating hinds (N = 19) started ovarian cycles 10 days later (P<0·01) and conceived 16 days later (P< 0·001) than did 13 weaned hinds. There was no evidence, from plasma progesterone values, of silent oestrus at the start of the season. Progestagen/PMSG treatment induced early ovulations in 8 anoestrous hinds but fertility was low, only 2 conceiving and giving birth. Pregnant hinds (N = 42) had high plasma concentrations of progesterone (mean 3–5 ng/ml) which declined just before parturition. more...