Postmeiotic germ cells require the lactate produced by the adjacent Sertoli cells (SCs) as their sole energy fuels. Lactate production in SCs is elaborately regulated by monitoring the transcription of the lactate dehydrogenase A (Ldha) gene. However, the transcription factors that are responsible for the control of Ldha transcription in SCs remain ill defined. Herein, the expression of forkhead box Q1 (FOXQ1), a central modulator of glucose metabolism in liver, was demonstrated in mouse testis throughout postnatal development, with maximum levels in adult specimens. At this age, FOXQ1 was immunolocalized in the nuclei of the functionally mature SCs. Testicular levels of FOXQ1 were overtly modulated by germ cells (GCs)-derived IL-1α, in a dose- and time-dependent manner. To further clarify the biological functions of FOXQ1, we disrupted the mouse Foxq1 gene using a Cas9/RNA-mediated gene targeting strategy. Foxq1^−/− males were subfertile and showed oligoasthenozoospermia due to lactate deficiency. Moreover, we provided the molecular evidence that FOXQ1 may regulate lactate production by directly targeting the transactivation of the Ldha gene in SCs. From a functional standpoint, overexpression of the exogenous Ldha ameliorated Foxq1 deficiency-impaired lactate synthesis in the SCs^Foxq1−/− cells. Thus, these findings collectively underscore a reproductive facet of this recently characterized transcription factor, which may operate as a novel transcriptional integrator linking energy homeostasis and nursery function in SCs.

减数分裂后的生殖细胞需要相邻的支持细胞 (SC) 产生的乳酸作为其唯一的能量燃料。通过监测乳酸脱氢酶 A ( Ldha ) 基因的转录，对 SCs 中的乳酸产生进行了精心调节。然而，负责控制Ldha的转录因子SCs 中的转录仍然不明确。在此，叉头盒 Q1 (FOXQ1) 是肝脏葡萄糖代谢的中枢调节剂，在整个出生后发育的小鼠睾丸中均得到证实，在成人标本中表达水平最高。在这个年龄，FOXQ1 免疫定位于功能成熟的 SCs 的细胞核中。FOXQ1 的睾丸水平受生殖细胞 (GC) 衍生的 IL-1α 以剂量和时间依赖性方式明显调节。为了进一步阐明 FOXQ1 的生物学功能，我们使用 Cas9/RNA 介导的基因靶向策略破坏了小鼠 Foxq1 基因。Foxq1 ^-/-由于乳酸缺乏，雄性不育并表现出少弱精子症。此外，我们提供了分子证据，表明 FOXQ1 可以通过直接靶向SC 中Ldha基因的反式激活来调节乳酸的产生。从功能的角度来看，外源性Ldha 的过表达改善了 SCs ^Foxq1-/-细胞中Foxq1 缺陷导致的乳酸合成。因此，这些发现共同强调了这种最近表征的转录因子的生殖方面，它可以作为连接 SCs 中能量稳态和保育功能的新型转录整合因子发挥作用。