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Mechanisms underlying reduced fertility in anovular dairy cows

机译：无性奶牛生育力降低的潜在机制

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Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF(2 alpha) in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were downregulated, whereas genes linked to apoptosis and autophagy were upregulated in Day 15 conceptuses collected from anovular cows compared with estrous cyclic counterparts. Similar changes in conceptus transcriptome were not observed in estrous cyclic cows induced to ovulate follicles that grew under low and high concentrations of progesterone, indicating an effect of anovulation on embryonic development that is not mediated solely by progesterone concentrations before ovulation. Finally, risk factors for anovulation have direct effects on embryo development and uterine receptivity to pregnancy that complement those determined by insufficient concentrations of progesterone during follicular growth. One approach to minimize the impact of anovulation on fertility is supplementation with progesterone during recruitment, selection and final stages of development of the preovulatory follicle. It is suggested that a minimum of 2.0 ng/mL of progesterone is needed during growth of the preovulatory follicle to achieve P/AI similar to that of cows growing the preovulatory follicle during diestrus. (C) 2016 Elsevier Inc. All rights reserved.
机译：分娩后恢复排卵是一个协调的过程，涉及到肝脏中GH /胰岛素样生长因子1轴的重新结合，卵泡发育和类固醇生成的增加以及下丘脑中雌二醇的负反馈的消除。与早期哺乳期广泛的负能量平衡相关的传染病和代谢紊乱破坏了该途径，并延迟了产后首次排卵。产后无排卵期延长对奶牛的生育能力产生长期影响，包括缺乏自发性发情，每次人工授精（P / AI）减少妊娠，以及增加流产的风险。接受AI同步程序的无奶牛中的孕酮浓度不足以优化卵泡成熟，卵母细胞功能以及随后的AI生育能力。在孕激素浓度低下发育的第一波卵泡的排卵会降低受精后第一周的胚胎质量和奶牛的P / AI。尽管还没有确定无排卵和低浓度孕酮损害卵母细胞质量的具体机制，但对持续性卵泡的研究支持过早恢复减数分裂和母体RNA降解。排卵前未达最佳浓度的孕酮也增加了催产素在随后的发情周期中对催产素的合成，这解释了与无发情的循环群伴侣相比，在无生育期母牛首次AI产后短黄体期发生率更高。有人提出，动情周期早期自发性黄体溶解的增加是导致无性奶牛早期胚胎损失的机制之一。在妊娠的植入前阶段，无排卵还导致细长概念的基因表达发生重大变化。与发情的环状对应物相比，在第15天从无奶牛收集的概念中，与能量代谢控制和DNA修复有关的转录物被下调，而与凋亡和自噬相关的基因被上调。在低浓度和高浓度孕酮诱导的排卵卵泡的动情周期奶牛中，未观察到概念转录组的类似变化，这表明排卵对排卵的影响并不仅仅由排卵前的孕酮浓度介导。最后，无排卵的危险因素直接影响胚胎发育和子宫对妊娠的接受能力，与卵泡生长过程中孕激素浓度不足所确定的那些因素相辅相成。使排卵对生育的影响最小化的一种方法是在排卵前卵泡的募集，选择和发育的最后阶段补充孕酮。建议在排卵前卵泡生长期间至少需要2.0 ng / mL的孕酮才能达到P / AI，类似于在二头肌中生长排卵前卵的母牛。 （C）2016 Elsevier Inc.保留所有权利。

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