Department of Animal and Dairy Sciences, Mississippi State University, Mississippi State, MS, 39762, USA.
J Anim Sci. 2022 Dec 1;100(12). doi: 10.1093/jas/skac372.
Compromised pregnancies result in a poorly functioning placenta restricting the amount of oxygen and nutrient supply to the fetus resulting in intrauterine growth restriction (IUGR). Supplementing dietary melatonin during a compromised pregnancy increased uteroplacental blood flow and prevented IUGR in a seasonal-dependent manner. The objectives were to evaluate seasonal melatonin-mediated changes in temporal alterations of the bovine placental vascularity and transcript abundance of clock genes, angiogenic factors, and nutrient sensing genes in 54 underfed pregnant Brangus heifers (Fall, n = 29; Summer, n = 25). At day 160 of gestation, heifers were assigned to treatments consisting of adequately fed (ADQ-CON; 100% NRC; n = 13), nutrient restricted (RES-CON; 60% NRC; n = 13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). The animals were fed daily at 0900 hours until day 240 where Cesarean sections were performed in the morning (0500 hours) or afternoon (1300 hours) for placentome collections. In both seasons, we observed a temporal alteration of the core clock genes in the cotyledonary tissue in a season-dependent manner. In the fall, ARNTL, CLOCK, NR1D1, and RORA transcript abundance were decreased (P ≤ 0.05) in the afternoon compared to the morning; whereas in the summer, ARNTL, PER2, and RORA expression were increased (P ≤ 0.05) in the afternoon. Interestingly, in both seasons, there was a concomitant temporal increase (P ≤ 0.05) of cotyledonary blood vessel perfusion and caruncular melatonin receptor 1A transcript abundance. Melatonin supplementation did not alter the melatonin receptor 1A transcript abundance (P > 0.05), however, in the summer, melatonin supplementation increased cotyledonary VEGFA, CRY1, and RORA (P ≤ 0.05) transcript abundance. In addition, during the summer the placentomes from underfed dams had increased average capillary size and HIF1α transcript abundance compared to those adequately fed (P ≤ 0.05). In conclusion, these data indicate increased cotyledonary blood vessel size and blood distribution after feeding to better facilitate nutrient transport. Interestingly, the maternal nutritional plane appears to play a crucial role in regulating the bovine placental circadian clock. Based on these findings, the regulation of angiogenic factors and clock genes in the bovine placenta appears to be an underlying mechanism of the therapeutic effect of dietary melatonin supplementation in the summer.
受损妊娠会导致胎盘功能不良，限制胎儿的氧气和营养供应，导致宫内生长受限（IUGR）。在受损妊娠期间补充膳食褪黑素可增加胎盘血流，并以季节性依赖的方式预防 IUGR。本研究的目的是评估褪黑素介导的季节性变化对牛胎盘血管生成和时钟基因、血管生成因子和营养感应基因转录丰度的时间改变，共纳入 54 头处于妊娠中期的 Brangus 小母牛（秋季，n=29；夏季，n=25）。在妊娠 160 天时，小母牛被分为以下处理组：充足喂养（ADQ-CON；100% NRC；n=13）、限制喂养（RES-CON；60% NRC；n=13）和 ADQ 或 RES 补充 20 mg/d 褪黑素（ADQ-MEL，n=13；RES-MEL，n=15）。动物每天在 0900 时喂食，直到第 240 天，然后在早上（0500 时）或下午（1300 时）进行剖腹产，以采集胎盘组织。在两个季节中，我们观察到胎盘中核心时钟基因的时间改变，且呈季节性依赖方式。在秋季，与上午相比，下午 ARNTL、CLOCK、NR1D1 和 RORA 的转录丰度降低（P≤0.05）；而在夏季，下午 PER2 和 RORA 的表达增加（P≤0.05）。有趣的是，在两个季节中，胎盘血管灌注和 caruncular 褪黑素受体 1A 的转录丰度都呈现出时间上的同步增加（P≤0.05）。褪黑素补充并未改变褪黑素受体 1A 的转录丰度（P＞0.05），然而，在夏季，褪黑素补充增加了胎盘中 VEGFA、CRY1 和 RORA 的转录丰度（P≤0.05）。此外，在夏季，与充足喂养的小母牛相比，营养不足的小母牛胎盘中平均毛细血管大小和 HIF1α 的转录丰度增加（P≤0.05）。综上所述，这些数据表明，进食后胎盘中的血管大小和血液分布增加，以更好地促进营养物质的运输。有趣的是，母体营养水平似乎在调节牛胎盘生物钟方面起着至关重要的作用。基于这些发现，膳食褪黑素补充的治疗作用的潜在机制可能是对牛胎盘血管生成因子和时钟基因的调节。
