维甲酸直接诱导鸡原始生殖细胞启动并完成减数分裂

维甲酸（RA）在胚胎期生殖细胞启动减数分裂过程中发挥重要的调控作用,但RA与性腺细胞的作用机制及其能否诱导生殖细胞完成整个减数分裂生成配子的问题尚不清楚.本文以鸡原始生殖细胞体外无饲养层培养体系为模型,避开性腺体细胞的影响,研究RA诱导PGC进入减数分裂的作用机理.研究发现,在无体细胞的情况下,RA显著上调鸡胚PGC中STRA8,SYCP3和DMC1的mRNA和蛋白表达水平,从而促进其进入减数分裂;同时,流式细胞分析和吉姆萨染色结果表明,RA能使鸡胚PGC经历各个减数分裂时期,最终生成36.5%～58.4%单倍体生殖细胞;此外,本实验还对雌性和雄性PGC对RA的应答能力进行了研究,发现两者对RA的敏感程度相似.综上所述,RA能直接诱导PGC启动并完成整个减数分裂过程,生成单倍体生殖细胞,无需体细胞或其他因子的介导.这为临床上治疗不孕不育及配子形成的机理研究提供了基础.

Retinoic Acid Directly Regulates the Initiation and Completion of Meiosis in Chicken Primordial Germ Cells

Retinoic acid （RA） plays a key role in regulating meiotic initiation in fetal germ cells; however, it is not clear how RA interacts with gonadal cells and whether RA possesses the ability to induce germ cells to complete meiosis. In this study, we utilized purified chicken primordial germ cells （PGCs） culture system to investigate the direct effects of RA on entry of PGCs into meiosis, while excluding any effects from gonadal somatic cells. Results showed that RA significantly upregulated the mRNA and protein expression levels of STRAS, SYCP3 and DMC1 in chicken PGCs, thereby inducing entry of PGC into meiosis. Meanwhile, we found that RA is able to induce PGC to undergo all stages of meiotic phage, eventually leading to haploid cell formation, which was determined by giemsa stain and FACS analysis. Furthermore, our work revealed that the sensitivities of male and female PGCs in response to RA are quite similar. In conclusion, RA directly induces PGC to initiate and complete meiosis to produce haploid cells, which do not need the involvement of gonadal somatic cells or other factors. This work provides a platform for clinical application of infertility, as well as mechanistic understanding of gametogenesis.