Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA.
Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA Department of Human Oncology, University of Wisconsin, Madison, WI, USA.
Reprod Sci. 2015 Feb;22(2):250-7. doi: 10.1177/1933719114542026. Epub 2014 Jul 16.
Adenine nucleotide translocase (Ant) facilitates the exchange of adenosine triphosphate across the mitochondrial inner membrane and plays a critical role for bioenergetics in eukaryotes. Mice have 3 Ant paralogs, Ant1 (Slc25a4), Ant2 (Slc25a5), and Ant4 (Slc25a31), which are expressed in a tissue-dependent manner. We previously identified that Ant4 was expressed exclusively in testicular germ cells in adult mice and essential for spermatogenesis and subsequently male fertility. Further investigation into the process of spermatogenesis revealed that Ant4 was particularly highly expressed during meiotic prophase I and indispensable for normal progression of leptotene spermatocytes to the stages thereafter. In contrast, the expression and roles of Ant4 in female germ cells have not previously been elucidated. Here, we demonstrate that the Ant4 gene is expressed during embryonic ovarian development during which meiotic prophase I occurs. We confirmed embryonic ovary-specific Ant4 expression using a bacterial artificial chromosome transgene. In contrast to male, however, Ant4 null female mice were fertile although the litter size was slightly decreased. They showed apparently normal ovarian development which was morphologically indistinguishable from the control animals. These data indicate that Ant4 is a meiosis-specific gene expressed during both male and female gametogenesis however indispensable only during spermatogenesis and not oogenesis. The differential effects of Ant4 depletion within the processes of male and female gametogenesis may be explained by meiosis-specific inactivation of the X-linked Ant2 gene in male, a somatic paralog of the Ant4 gene.
腺嘌呤核苷酸转位酶 (Ant) 促进三磷酸腺苷在线粒体内膜之间的交换,在真核生物的生物能量学中起着关键作用。小鼠有 3 个 Ant 基因的同源物,Ant1(Slc25a4)、Ant2(Slc25a5)和 Ant4(Slc25a31),它们以组织依赖性的方式表达。我们之前发现 Ant4 仅在成年小鼠的睾丸生殖细胞中表达,对精子发生和随后的雄性生育能力至关重要。对精子发生过程的进一步研究表明,Ant4 在减数分裂前期 I 中表达特别高,对于从细线期精母细胞向随后的阶段的正常进展是必不可少的。相比之下,Ant4 在雌性生殖细胞中的表达和作用尚未阐明。在这里,我们证明 Ant4 基因在发生减数分裂前期 I 的胚胎卵巢发育过程中表达。我们使用细菌人工染色体转基因证实了胚胎卵巢特异性 Ant4 表达。然而,与雄性相反,Ant4 基因缺失的雌性小鼠是可育的,尽管产仔数略有减少。它们表现出明显正常的卵巢发育,在形态上与对照动物没有区别。这些数据表明 Ant4 是一个在雄性和雌性配子发生过程中表达的减数分裂特异性基因,但在精子发生中不可或缺,而在卵发生中则不是。Ant4 在雄性配子发生和雌性配子发生过程中的不同作用可能是由于 Ant2 基因(Ant4 基因的体节同源物)在减数分裂过程中的特异性失活造成的。