Biol Reprod：低蛋白质饮食让后代易患成年期高血压

研究已经显示，饮食蛋白质低的母亲的后代更可能在成年期出现高血压。美国德克萨斯大学加尔维斯顿医学分部的Gao博士、Yallampalli博士和Yallampalli博士如今在国际杂志Biology of Reproduction上报告说，对于大鼠，母亲的与低蛋白质饮食有关的睾丸激素水平高是由一种让睾丸激素失去活性的酶的活动减少导致的，这让更多的睾丸激素到达了胎儿并增加了后代对成年期高血压的易感性。

胎儿程序化（fetal programming）是一个用于描述母亲的压力对未出生的子女的出生时的身体特性以及长期健康的影响的一个术语。由于胎盘在激素制造和营养输送方面的关键作用以及它对环境扰动的易感性，它被认为是胎儿程序化的一个重要贡献者。

近来，一项研究发现蛋白质限制让怀孕大鼠的血浆睾丸激素水平加倍。升高的睾丸激素水平与人类的先兆子痫以及多囊性卵巢综合征等与怀孕有关的并发症有关联，而且正在出现的证据提示睾丸激素可能在高血压的胎儿程序化方面起到了一个作用。

Gao等人提出了一种假说，即睾丸激素水平的增加或者是由于产生睾丸激素的酶活动的增加导致的，或者是由于减少睾丸激素的一种酶Hsd17b2的活动减少导致的。Hsd17b2把睾丸激素转化成了一种效力较小的雄性激素雄烯二酮。

该研究组发现，Hsd17b2在大鼠体内的表达在胎盘的两个部分受到了蛋白质限制的影响。它在负责激素制造的连接带增加，但是在迷宫层减少，而后者对于营养从母亲输送给胎儿具有关键作用，也起到了一个保护性屏障的作用。

根据这项新发现，Gao等人提出Hsd17b2在保护性迷宫层表达的减少可能让更多的睾丸激素到达胎儿体内并且在高血压的胎儿程序化方面起到了作用。

Hsd17b2是唯一受妊娠期蛋白质限制影响的参与睾丸激素制造的酶的这一发现提示Hsd17b2在调节母胎界面的睾丸激素水平方面具有重要的作用；需要进一步的研究从而确定它的准确功能。

doi:10.1095/biolreprod.112.100479
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Gestational Protein Restriction Reduces Expression of Hsd17b2 in Rat Placental Labyrinth

Haijun Gao, Uma Yallampalli and Chandra Yallampalli

Accumulating evidence strongly supports that testosterone may be a key player in fetal programming on hypertension. It was reported that gestational protein restriction doubles the plasma testosterone levels in pregnant rats. In this study, we hypothesized that elevated testosterone levels in response to gestational protein restriction were caused by enhanced expression of steroidogenic enzymes or impaired expression of Hsd17b2, a known testosterone inactivator that converts testosterone to androstenedione in placenta. Pregnant Sprague Dawley rats were fed normal (20% protein, control; n = 10) or a low protein diet (6% protein, PR; n = 10) from day 1 of pregnancy until sacrificed at days 14, 18 or 21. Junctional (JZ) and labyrinth (LZ) zones of placenta were collected for expression assay on steroidogenic genes (Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b2 and Sdr5a1) by Real-time PCR. The main findings include: 1) expressions of Cyp11a1, Hsd3b1 and Cyp17a1 in JZ were not affected by diet, but affected by day of pregnancy; 2) expression of Hsd17b2 in both female and male JZs was remarkably increased by PR at days 18 and 21 of pregnancy; 3) expressions of Hsd17b2 were reduced by PR in both female and male LZ at day 18 of pregnancy, and in female LZ at day 21 of pregnancy; 4) expression of Sdr5a1 in LZ was not affected by day of pregnancy, gender and diet. These results indicate that in response to gestational protein restriction, Hsd17b2 may be a key regulator of testosterone levels and associated activities in placental zones apparently in a paradox manner.