Jasurda Jake S, Jung Deborah O, Froeter Erin D, Schwartz David B, Hopkins Torin D, Farris Corrie L, McGee Stacey, Narayan Prema, Ellsworth Buffy S
Department of Physiology, Southern Illinois University, Carbondale, Illinois.
Biol Reprod. 2014 Jan 9;90(1):4. doi: 10.1095/biolreprod.113.112375. Print 2014 Jan.
Fertility is dependent on the hypothalamic-pituitary-gonadal axis. Each component of this axis is essential for normal reproductive function. Mice with a mutation in the forkhead transcription factor gene, Foxp3, exhibit autoimmunity and infertility. We have previously shown that Foxp3 mutant mice have significantly reduced expression of pituitary gonadotropins. To address the role of Foxp3 in gonadal function, we examined the gonadal phenotype of these mice. Foxp3 mutant mice have significantly reduced seminal vesicle and testis weights compared with Foxp3(+/Y) littermates. Spermatogenesis in Foxp3 mutant males is arrested prior to spermatid elongation. Activation of luteinizing hormone signaling in Foxp3 mutant mice by treatment with human chorionic gonadotropin significantly increases seminal vesicle and testis weights as well as testicular testosterone content and seminiferous tubule diameter. Interestingly, human chorionic gonadotropin treatments rescue spermatogenesis in Foxp3 mutant males, suggesting that their gonadal phenotype is due primarily to a loss of pituitary gonadotropin stimulation rather than an intrinsic gonadal defect.
生育能力取决于下丘脑 - 垂体 - 性腺轴。该轴的每个组成部分对于正常生殖功能都至关重要。叉头转录因子基因Foxp3发生突变的小鼠表现出自身免疫和不育。我们之前已经表明，Foxp3突变小鼠垂体促性腺激素的表达显著降低。为了研究Foxp3在性腺功能中的作用，我们检查了这些小鼠的性腺表型。与Foxp3(+/Y)同窝小鼠相比，Foxp3突变小鼠的精囊和睾丸重量显著降低。Foxp3突变雄性小鼠的精子发生在精子细胞伸长之前就停止了。用人绒毛膜促性腺激素处理激活Foxp3突变小鼠的促黄体生成素信号，可显著增加精囊和睾丸重量以及睾丸睾酮含量和曲细精管直径。有趣的是，人绒毛膜促性腺激素处理可挽救Foxp3突变雄性小鼠的精子发生，这表明它们的性腺表型主要是由于垂体促性腺激素刺激的丧失，而不是内在的性腺缺陷。
