Roles of estrogens in fish sexual plasticity and sex differentiation
Roles of estrogens in fish sexual plasticity and sex differentiation
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雌激素在鱼类性可塑性和性别分化中的作用
DOI：
10.1016/j.ygcen.2018.11.015
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发表时间：
2019-06-01
影响因子：
2.7
通讯作者：
Wang, Deshou
中科院分区：
文献类型：
--
作者：
Li, Minghui;Sun, Lina;Wang, Deshou
在性腺未分化阶段，通过外源性雌激素（E2）或芳香化酶抑制剂阻断内源性雌激素的合成，可以逆转鱼类的性别，称为初级性逆转（PSR）。最近的研究表明，雌雄异株鱼类在性别决定/分化后仍保持其性别可塑性。分化的卵巢可以转分化为功能性睾丸，反之亦然，分化的睾丸可以转分化为卵巢。通过对这两种继发性反转（SSR）模型的分析，发现雄-雌性反转的诱导是从背侧（靠近血管）到腹侧开始的，而雌-雄性反转的诱导是从腹侧到背侧开始的。内源性雌激素的下调是卵巢转分化的前提。然而，单独的外源性雌激素不足以诱导睾丸向卵巢分化。给予E2并同时阻断雄激素合成可诱导睾丸转分化。因此，内源性雌激素对卵巢分化/维持至关重要，雄激素对睾丸维持至关重要。最近，基因组编辑技术的遗传学研究也表明，Cyp 19 a1 a的破坏诱导睾丸发育，表明Cyp 19 a1 a是雌激素合成和卵巢分化/维持所必需的关键基因。敲除雄性途径基因或过表达雌性途径基因可上调cyp 19 a1 a的表达，提高雌激素水平，从而促进卵巢发育。反之，敲除雌性途径基因或过表达雄性途径基因可下调cyp 19 a1 a的表达，降低雌激素水平，促进睾丸发育（转基因或敲除性逆转，TSR）。cyp 19 a1 a的表观遗传调控在自然性逆转中起着重要作用，但其与PSR、SSR和TSR的关系还有待进一步研究。总之，这些研究进一步强调了内源性雌激素在鱼类性别分化/维持中的重要作用。
Fish sex could be reversed at the undifferentiated stage of gonad by administration of exogenous estrogen (E2) or blockade of endogenous estrogen synthesis with aromatase inhibitors, which is designated as primary sex reversal (PSR). Recent studies have well demonstrated that gonochoristic fish maintain their sexual plasticity after sex determination/differentiation. The differentiated ovary could be transdifferentiated into functional testis, and vice versa, the differentiated testis could be transdifferentiated into ovary. By analyzing these two secondary sex reversal (SSR) models, it was found that induction of male-to-female sex reversal initiates from dorsal (near the blood vessel) to the ventral, while induction of female-to-male sex reversal initiates from the ventral to dorsal. Down regulation of endogenous estrogen is the prerequisite for the ovarian transdifferentiation. However, exogenous estrogen alone is not sufficient for inducing differentiated testis to ovary. Administration of E2 and simultaneous blockage of androgen synthesis could induce testicular transdifferentiation. Therefore, endogenous estrogen is critical for the ovarian differentiation/maintenance and androgen is critical for testicular maintenance. Recently, genetic studies with genome editing technologies also showed that disruption of Cyp19a1a induced testicular development, indicating that cyp19a1a is the key gene essential for estrogen synthesis and ovary differentiation/maintenance. Knockout of male pathway genes or overexpression of female pathway genes could up-regulate cyp19a1a expression and increase estrogen level so as to promote ovary. Conversely, knockout of female pathway genes or overexpression of male pathway genes could down-regulate cyp19a1a expression and decrease estrogen level so as to promote testis (transgenic or knockout sex reversal, TSR). Epigenetic regulation of cyp19a1a play a critical role in natural sex reversal (NSR), but its relation with PSR, SSR and TSR needs further detailed investigations. In all, these studies further highlighted the important roles of endogenous estrogens in fish sex differentiation/maintenance.