INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France.
France CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France.
Reprod Biol Endocrinol. 2019 Feb 18;17(1):25. doi: 10.1186/s12958-019-0467-x.
In dairy cows, the energy cost of milk yield results in a negative energy balance (EB) and body fat mobilization that impairs reproductive efficiency. Emerging evidence suggests that the novel adipokines, Retinoic acid receptor responder protein 2 (RARRES2), and its main receptor, Chemokine-like receptor 1 (CMKLR1) are involved in the regulation of metabolic and ovarian functions. So, we investigated in a first experiment the plasma RARRES2, and RARRES2 and CMKLR1 mRNA expression levels in subcutaneous adipose tissue (SAT) and granulosa cells (GC) at different times of body fat mobilization in dairy cows (4, 8, 20 and 44 weeks postpartum, wk. pp. for SAT and 8, 20 and 44 wk. pp. for GC). Then, in a second experiment we examined the effect of high (HE) and low energy (LE) diets on the RARRES2 system and its links with metabolic and reproductive parameters.
The first experiment included 9 animals fed with HE diet from 4 to 44 wk. pp. and the second one included animals fed either a HE diet (n = 8) or a LE diet (n = 8) from - 4 to 16 wk. peripartum. In both experiments, various metabolic and reproductive parameters were determined and associated with plasma RARRES2 as measured by bovine ELISA. RARRES2 and CMKLR1 mRNA expression levels were analyzed by RT-qPCR in SAT after biopsy and GC after aspiration of follicles.
Plasma RARRES2 levels were higher at 4 wk. pp. as compared to 20 and 44 wk. pp. and they were positively correlated with body fat mobilization and milk yield. RARRES2 and CMKLR1 mRNA expression levels increased from 4 to 8 wk. pp. (fat mobilization, EB < 0) and remained unchanged at 20 and 44 wk. pp. (fat reconstitution, EB > 0) as compared to 4 wk. pp. in SAT. RARRES2 and CMKLR1 mRNA levels decreased from 8 to 44 wk. pp. in GC from small follicles. In the second experiment, plasma RARRES2 increased from - 4 to 8 wk. peripartum similarly in both LE and HE cows. In addition, the area under of plasma RARRES2 curve was highly negatively associated with the number of small follicles obtained in HE animals during the cycle before the first artificial insemination. In SAT of HE cows, RARRES2 mRNA expression decreased at 1 wk. pp. compared to - 4 and 16 wk. peripartum whereas opposite expression patterns were obtained for CMKLR1. Similar results were observed for CMKLR1 mRNA expression in LE cows while there was no variation in RARRES2 mRNA expression. Moreover, RARRES2 mRNA was higher expressed in LE than in HE cows at 1 wk. pp.
The lactation-induced fat and energy mobilization influenced plasma RARRES2 profile and mRNA expression pattern of RARRES2 and CMKLR1 similarly in both SAT and GC. In addition, the energy content of the diet did not affect plasma RARRES2 but it altered RARRES2 mRNA expression in SAT and the area under the curve of plasma RARRES2 that was negatively associated to the number of small follicles in HE animals. Thus, RARRES2 could be a metabolic or ovarian signal involved in the interactions between metabolic and reproductive functions in dairy cows.
在奶牛中，产奶的能量成本导致负能量平衡（EB）和体脂动员，从而损害生殖效率。新出现的证据表明，新型脂肪因子视黄酸受体应答蛋白 2（RARRES2）及其主要受体趋化因子样受体 1（CMKLR1）参与了代谢和卵巢功能的调节。因此，我们在第一项实验中研究了奶牛不同体脂动员时间（4、8、20 和 44 周产后，SAT 为 4 周，GC 为 8、20 和 44 周）的皮下脂肪组织（SAT）和颗粒细胞（GC）中血浆 RARRES2 以及 RARRES2 和 CMKLR1 mRNA 表达水平。然后，在第二项实验中，我们检查了高（HE）和低能量（LE）饮食对 RARRES2 系统及其与代谢和生殖参数的关系的影响。
第一项实验包括 9 头从 4 周到 44 周产后哺乳期喂食 HE 饮食的动物，第二项实验包括从-4 周到产后 16 周喂食 HE 饮食（n = 8）或 LE 饮食（n = 8）的动物。在这两项实验中，测定了各种代谢和生殖参数，并与通过牛 ELISA 测量的血浆 RARRES2 相关联。通过 SAT 活检和 GC 卵泡抽吸后进行 RT-qPCR 分析 RARRES2 和 CMKLR1 mRNA 表达水平。
与 20 和 44 周产后相比，4 周产后血浆 RARRES2 水平更高，与体脂动员和产奶量呈正相关。RARRES2 和 CMKLR1 mRNA 表达水平从 4 周到 8 周（脂肪动员，EB < 0）增加，并且在 20 和 44 周（脂肪重建，EB > 0）与 4 周时相比在 SAT 中保持不变。从 8 周到 44 周，GC 中小卵泡的 RARRES2 和 CMKLR1 mRNA 水平下降。在第二项实验中，LE 和 HE 奶牛的血浆 RARRES2 从-4 周到产后 8 周相似地增加。此外，在 HE 动物第一次人工授精前的周期中获得的小卵泡数量的血浆 RARRES2 曲线下面积与小卵泡数量呈高度负相关。在 HE 奶牛的 SAT 中，与-4 周和产后 16 周相比，RARRES2 mRNA 表达在 1 周时下降，而 CMKLR1 则表现出相反的表达模式。在 LE 奶牛中也观察到类似的 CMKLR1 mRNA 表达变化，而 RARRES2 mRNA 表达没有变化。此外，LE 奶牛的 RARRES2 mRNA 表达水平高于 HE 奶牛的 RARRES2 mRNA 表达水平在 1 周时。
哺乳期诱导的脂肪和能量动员影响了 SAT 和 GC 中 RARRES2 和 CMKLR1 的血浆 RARRES2 谱和 mRNA 表达模式。此外，饮食的能量含量不会影响血浆 RARRES2，但会改变 SAT 中的 RARRES2 mRNA 表达，并且血浆 RARRES2 的曲线下面积与 HE 动物中小卵泡的数量呈负相关。因此，RARRES2 可能是一种代谢或卵巢信号，参与奶牛代谢和生殖功能之间的相互作用。
