Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, Universidade de São Paulo, Pirassununga, São Paulo, Brazil.
Department of Veterinary Medicine, School of Animal Science and Food Engineering, Universidade de São Paulo, Pirassununga, São Paulo, Brazil.
Sci Rep. 2019 Jul 17;9(1):10358. doi: 10.1038/s41598-019-46775-8.
Semen fertilizing potential is dependent upon the morphological, functional and molecular attributes of sperm. Sperm microRNAs (miRNAs) were recently shown to hold promise regarding their association with different fertility phenotypes. However, their role in fertility regulation remains to be determined. We postulated that sperm miRNAs might regulate early embryonic development. From this perspective, sperm quality and 380 sperm miRNAs were investigated in frozen-thawed semen from high (HF; 54.3 ± 1.0% pregnancy rate) and low (LF; 41.5 ± 2.3%) fertility bulls. Out of nine miRNAs that showed different levels in sperm cells, miR-216b was present at lower levels in HF sperm cells and zygotes. Among miR-216b target genes (K-RAS, BECN1 and JUN), K-RAS, related to cell proliferation, revealed a higher level in HF two-cell embryos. First cleavage rate, blastocyst cell number and division number were also higher in HF. In addition, by using a model based on polyspermy embryos, we demonstrated an increase in miR-216b levels in zygotes associated with sperm cell entry. Our results shed light on a possible mechanism of paternal contribution involving sperm-borne miR-216b that modulates levels of miR-216b in zygotes and K-RAS in two-cell embryos. This modulation might regulate early development by interfering with the first cleavage and blastocyst quality.
精子的受精能力取决于精子的形态、功能和分子特性。最近的研究表明，精子 microRNAs（miRNAs）与不同的生育表型相关，具有一定的应用前景。然而，其在生育调节中的作用仍有待确定。我们推测精子 miRNAs 可能参与调节早期胚胎发育。基于这一观点，我们研究了冷冻解冻精液中精子质量和 380 个精子 miRNAs 在高（HF；54.3±1.0%妊娠率）和低（LF；41.5±2.3%妊娠率）生育力公牛中的情况。在九个精子细胞中存在不同水平的 miRNA 中，miR-216b 在 HF 精子细胞和受精卵中水平较低。在 miR-216b 的靶基因（K-RAS、BECN1 和 JUN）中，与细胞增殖相关的 K-RAS 在 HF 二细胞胚胎中水平更高。HF 胚胎的第一次卵裂率、囊胚细胞数和分裂数也更高。此外，通过使用多精入卵胚胎模型，我们证明了与精子进入相关的受精卵中 miR-216b 水平升高。我们的研究结果揭示了一种可能的父本贡献机制，涉及精子携带的 miR-216b 调节受精卵中 miR-216b 和二细胞胚胎中 K-RAS 的水平。这种调节可能通过干扰第一次卵裂和囊胚质量来调节早期发育。
