BackgroundExercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed “myokines”. The purpose of this study was to examine the effects of high-intensity interval training (HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6 (IL-6), and recently identified myokines fibronectin type III domain-containing protein 5 (FNDC5) (irisin) and meteorin-like protein (METRNL).MethodsBoth before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males (20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise (HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples (vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery.ResultsBefore training, a single bout of HIIE increased IL-6 (p < 0.05) and METRNL (p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest (both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training (p < 0.05), and there was an overall increase in FNDC5 mRNA post-training (main effect of training, p < 0.05).ConclusionIn human skeletal muscle (1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT; (2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and (3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.

The major milestones in mouse placental development are well described, but our understanding is limited to how the placenta can adapt to damage or changes in the environment. By using stereology and expression of cell cycle markers, we found that the placenta grows under normal conditions not just by hyperplasia of trophoblast cells but also through extensive polyploidy and cell hypertrophy. In response to feeding a low protein diet to mothers prior to and during pregnancy, to mimic chronic malnutrition, we found that this normal program was altered and that it was influenced by the sex of the conceptus. Male fetuses showed intrauterine growth restriction (IUGR) by embryonic day (E) 18.5, just before term, whereas female fetuses showed IUGR as early as E16.5. This difference was correlated with differences in the size of the labyrinth layer of the placenta, the site of nutrient and gas exchange. Functional changes were implied based on up-regulation of nutrient transporter genes. The junctional zone was also affected, with a reduction in both glycogen trophoblast and spongiotrophoblast cells. These changes were associated with increased expression of Phlda2 and reduced expression of Egfr. Polyploidy, which results from endoreduplication, is a normal feature of trophoblast giant cells (TGC) but also spongiotrophoblast cells. Ploidy was increased in sinusoidal-TGCs and spongiotrophoblast cells, but not parietal-TGCs, in low protein placentas. These results indicate that the placenta undergoes a range of changes in development and function in response to poor maternal diet, many of which we interpret are aimed at mitigating the impacts on fetal and maternal health.

The present study evaluated possible modulation of the buck effect by nutritional and metabolic cues during the transition to the breeding season in adult goats with divergent bodyweight (BW) and body condition (BCS) at 27°N. In mid-February, goats (Boer × Spanish, n = 32) were assigned to receive one of the following two experimental diets to fulfill different allowances of nutritional requirements: (1) 100% (n = 16; BW = 52.3 ± 1.5 kg, BCS = 1.6 ± 0.1 units; T-100) or (2) 150% (n = 16; BW = 60.9 ± 2.4 kg, BCS = 1.6 ± 0.1 units; T-150) from February to August. Blood samples were collected to analyse thyroxine (T4), triiodothyronine (T3), non-esterified fatty acids (NEFA), triglycerides (Tg) and progesterone (P4). Final BW and BCS favoured (P < 0.001) the T-150 group (74.9 ± 2.8 v. 56.3 ± 1.4 kg, and 4.4 ± 0.2 v. 1.9 ± 0.1 units, respectively). However, mean values for NEFA, Tg, T3 and T4 did not differ (P > 0.05) between the experimental groups. Thereafter, in early August, half of the does in each diet treatment were randomly selected for determining the response to the ‘male effect’ (WM), forming the following two treatment groups: (1) T-100-WM (n = 8), or (2) T-150-WM (n = 8); the remaining does formed two groups without male exposure (WOM), as follows: (3) T-100-WOM (n = 8) and (4) T-150-WOM (n = 8). To evaluate ovarian activity, blood samples were collected from all does on Days 2–4 during the 14-day period after the male exposure. On Day 12, all does exposed to males (16/16), irrespective of the nutritional treatment, depicted ovulatory activity, whereas only 3/16 (18.75%) T-WOM does did, indicating a significant (P < 0.001) difference between these treatment groups. The increased nutritional level of the T-150 group during the anoestrous season did not result in an early onset of ovulatory activity. Does demonstrated similar metabolic hormones and concentrations of blood metabolites between the two nutritional treatments (100 v. 150% of the nutritional requirements), suggesting a high physiological plasticity between the groups, stabilising their metabolism according to the nutritional history female goats faced, and generating similar reproductive outcomes. The male effect seems to be enough to induce oestrus during the late anoestrous season, irrespective of BCS and BW.

Placental abnormalities have been sporadically implicated as a source of developmental heart defects. Yet it remains unknown how often the placenta is at the root of congenital heart defects (CHDs), and what the cellular mechanisms are that underpin this connection. Here, we selected three mouse mutant lines, Atp11a, Smg9 and Ssr2, that presented with placental and heart defects in a recent phenotyping screen, resulting in embryonic lethality. To dissect phenotype causality, we generated embryo- and trophoblast-specific conditional knockouts for each of these lines. This was facilitated by the establishment of a new transgenic mouse, Sox2-Flp, that enables the efficient generation of trophoblast-specific conditional knockouts. We demonstrate a strictly trophoblast-driven cause of the CHD and embryonic lethality in one of the three lines (Atp11a) and a significant contribution of the placenta to the embryonic phenotypes in another line (Smg9). Importantly, our data reveal defects in the maternal blood-facing syncytiotrophoblast layer as a shared pathology in placentally induced CHD models. This study highlights the placenta as a significant source of developmental heart disorders, insights that will transform our understanding of the vast number of unexplained congenital heart defects.