Estrogen receptor β-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life
Estrogen receptor β-mediated inhibition of male germ cell line development in mice by endogenous estrogens during perinatal life
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DOI：
10.1210/en.2003-1479
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发表时间：
2004-07-01
期刊：
影响因子：
4.8
通讯作者：
Habert, R
中科院分区：
文献类型：
--
作者：
Delbès, R;Levacher, C;Habert, R
流行病学、临床和实验研究表明，胎儿/新生儿期间过多接触雌激素可导致成年后生殖障碍和精子异常。然而，尚不清楚内源性雌激素浓度是否影响男性胎儿生殖细胞谱系的建立。我们通过研究雌激素受体 (ER) β 或 ERα 基因失活的小鼠的睾丸发育来解决这个问题。 ERbeta (ERbeta(-/-)) 的纯合失活使 2 日龄和 6 日龄新生儿的生殖母细胞数量增加了 50%。支持细胞和间质细胞的数量以及睾丸睾酮产生的水平不受影响，这表明雌激素直接作用于性母细胞。生殖母细胞数量的增加并不发生在胎儿时期，而是发生在出生后不久，此时生殖母细胞恢复有丝分裂和凋亡。这似乎是由末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记方法和裂解的 caspase-3 免疫组织化学检测评估的细胞凋亡率降低所致。最后，ERbeta 基因失活的杂合小鼠在生殖细胞数量、细胞凋亡和有丝分裂方面与 ERbeta(-/-) 同窝小鼠表现相似，表明这些细胞对雌激素与 ERbeta 的结合高度敏感。 ERα失活对新生儿生殖母细胞和支持细胞的数量没有影响。总之，这项研究首次证明内源性雌激素可以在生理上抑制男性生殖细胞的生长。这一发现可能对环境雌激素的潜在作用具有重要意义。
Epidemiological, clinical, and experimental studies have suggested that excessive exposure to estrogens during fetal/neonatal life can lead to reproductive disorders and sperm abnormalities in adulthood. However, it is unknown whether endogenous concentrations of estrogens affect the establishment of the male fetal germ cell lineage. We addressed this question by studying the testicular development of mice in which the estrogen receptor (ER) beta or the ERalpha gene was inactivated. The homozygous inactivation of ERbeta (ERbeta(-/-)) increased the number of gonocytes by 50% in 2- and 6-d-old neonates. The numbers of Sertoli and Leydig cells and the level of testicular testosterone production were unaffected, suggesting that estrogens act directly on the gonocytes. The increase in the number of gonocytes did not occur during fetal life but instead occurred just after birth, when gonocytes resumed mitosis and apoptosis. It seems to result from a decrease in the apoptosis rate evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method and cleaved caspase-3 immunohistochemical detection. Last, mice heterozygous for the ERbeta gene inactivation behaved similarly to their ERbeta(-/-) littermates in terms of the number of gonocytes, apoptosis, and mitosis, suggesting that these cells are highly sensitive to the binding of estrogens to ERbeta. ERalpha inactivation had no effect on the number of neonatal gonocytes and Sertoli cells. In conclusion, this study provides the first demonstration that endogenous estrogens can physiologically inhibit germ cell growth in the male. This finding may have important implications concerning the potential action of environmental estrogens.