Conserved microRNA mediates heating tolerance in germ cells versus surrounding somatic cells

Mammalian fertility is reduced during heat exposure in the summer, but is regained as temperatures decrease in the autumn again. However, the mechanism underlying the phenomenon remains unknown. We investigated heat stress tolerance of germ cells and their surrounding somatic cells, and discovered that microRNA ssc-ca-1 was upregulated after heat stress in cultured porcine granulosa cells (GCs), but not in serum-starved GCs. Ssc-ca-1 inhibited heat shock protein 70 (Hsp70) expression through its 3′- and 5′-UTRs. Although <i>Hsp70</i> mRNA transcription was induced in GCs by <i>in vivo</i> exposure to heat in the summer, ssc-ca-1 inhibited Hsp70 expression. In ovarian cultures, heat stress-induced Hsp70 expression in primordial but not in growing follicles; ssc-ca-1 expression did not change in primordial follicles, but increased in growing follicles. Consistently, ssc-ca-1 was present in testicular cells and exhibited the same function as in ovarian cells. It modulated the different Hsp70 expression between spermatogonial stem cells and Sertoli cells after scrotal heat stress. This mechanism is of relevance to mammalian fertility in parts of the world dominated by heat stress associated with global climate change.

夏季高温暴露会降低哺乳动物的生育能力，而随着秋季气温回落，生育能力可恢复至正常水平。然而，该现象背后的分子机制目前仍未阐明。本研究针对生殖细胞及其外周体细胞的热应激耐受性展开探究，发现在培养的猪卵泡颗粒细胞（porcine granulosa cells, GCs）中，微小RNA（microRNA）ssc-ca-1在热应激后表达上调，但在血清饥饿处理的GCs中未出现该表达上调现象。ssc-ca-1可通过其3'和5'非翻译区（untranslated regions, UTRs）抑制热休克蛋白70（heat shock protein 70, Hsp70）的表达。尽管夏季体内（in vivo）热暴露可诱导GCs中Hsp70 mRNA的转录，但ssc-ca-1仍可抑制Hsp70的蛋白表达。在卵巢体外培养体系中，热应激仅能诱导原始卵泡（primordial follicles）中的Hsp70表达，而无法影响生长卵泡（growing follicles）；ssc-ca-1在原始卵泡中表达无明显变化，但在生长卵泡中表达显著上调。与之相符的是，ssc-ca-1在睾丸细胞中同样存在，且功能与卵巢细胞中一致；阴囊热应激后，它可调控精原干细胞（spermatogonial stem cells）与支持细胞（Sertoli cells）之间的Hsp70表达差异。该机制与全球气候变化引发的高温胁迫频发地区的哺乳动物生育能力密切相关。