Rico-Leo Eva M, Moreno-Marín Nuria, González-Rico Francisco J, Barrasa Eva, Ortega-Ferrusola Cristina, Martín-Muñoz Patricia, Sánchez-Guardado Luis O, Llano Elena, Alvarez-Barrientos Alberto, Infante-Campos Ascensión, Catalina-Fernández Inmaculada, Hidalgo-Sánchez Matías, de Rooij Dirk G, Pendás Alberto M, Peña Fernando J, Merino Jaime M, Fernández-Salguero Pedro M
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain.
Laboratorio de Reproducción y Espermatología Equina, Hospital Veterinario, Universidad de Extremadura, Cáceres, Spain.
Open Biol. 2016 Dec;6(12). doi: 10.1098/rsob.160186.
Previous studies suggested that the aryl hydrocarbon receptor (AhR) contributes to mice reproduction and fertility. However, the mechanisms involved remain mostly unknown. Retrotransposon silencing by Piwi-interacting RNAs (piRNAs) is essential for germ cell maturation and, remarkably, AhR has been identified as a regulator of murine B1-SINE retrotransposons. Here, using littermate AhR and AhR mice, we report that AhR regulates the general course of spermatogenesis and oogenesis by a mechanism likely to be associated with piRNA-associated proteins, piRNAs and retrotransposons. piRNA-associated proteins MVH and Miwi are upregulated in leptotene to pachytene spermatocytes with a more precocious timing in AhR than in AhR testes. piRNAs and transcripts from B1-SINE, LINE-1 and IAP retrotransposons increased at these meiotic stages in AhR-null testes. Moreover, B1-SINE transcripts colocalize with MVH and Miwi in leptonema and pachynema spermatocytes. Unexpectedly, AhR males have increased sperm counts, higher sperm functionality and enhanced fertility than AhR mice. In contrast, piRNA-associated proteins and B1-SINE and IAP-derived transcripts are reduced in adult AhR ovaries. Accordingly, AhR-null female mice have lower numbers of follicles when compared with AhR mice. Thus, AhR deficiency differentially affects testis and ovary development possibly by a process involving piRNA-associated proteins, piRNAs and transposable elements.
先前的研究表明，芳烃受体（AhR）对小鼠的生殖和生育能力有影响。然而，其中涉及的机制大多仍不清楚。Piwi相互作用RNA（piRNA）介导的逆转座子沉默对于生殖细胞成熟至关重要，值得注意的是，AhR已被确定为小鼠B1-SINE逆转座子的调节因子。在这里，我们使用同窝出生的AhR基因敲除小鼠和野生型AhR小鼠，报告AhR通过一种可能与piRNA相关蛋白、piRNA和逆转座子相关的机制来调节精子发生和卵子发生的一般过程。在细线期到粗线期的精母细胞中，piRNA相关蛋白MVH和Miwi上调，且在AhR基因敲除小鼠的睾丸中比在野生型AhR小鼠的睾丸中出现得更早。在这些减数分裂阶段，AhR基因敲除小鼠睾丸中来自B1-SINE、LINE-1和IAP逆转座子的piRNA和转录本增加。此外，B1-SINE转录本在细线期和粗线期精母细胞中与MVH和Miwi共定位。出乎意料的是，与AhR基因敲除小鼠相比，AhR基因敲除小鼠的精子数量增加、精子功能增强且生育能力提高。相反，成年AhR基因敲除小鼠卵巢中的piRNA相关蛋白以及B1-SINE和IAP衍生的转录本减少。因此，与AhR小鼠相比，AhR基因敲除雌性小鼠的卵泡数量更少。因此，AhR缺陷可能通过涉及piRNA相关蛋白、piRNA和转座元件的过程对睾丸和卵巢发育产生不同影响。
