Males and females may experience different effects of early-life adversity on life-long health. One hypothesis is that male foetuses invest more in foetal growth and relatively less in placental growth, and that this makes them susceptible to poor nutrition in utero, particularly if nutrition is reduced part-way through gestation. Our objectives were to examine whether (1) food and/ or protein restriction in rats and mice has consistent sex-dependent effects, (2) sex-dependency differs between types of outcomes, and (3) males are more severely affected when restriction starts part-way through gestation. PubMed and Web of Science were searched to identify eligible studies. Eligible studies described controlled experiments that restricted protein or food during gestation in rats or mice, examined physiological traits in offspring from manipulated pregnancies, and tested whether effects differed between males and females. Our search identified 292 articles, of which the full texts of 72 were assessed, and 65 were included for further synthesis. A majority (50) used Wistar or Sprague-Dawley rats and so these were the primary focus. Among studies in which maternal diet was restricted for the duration of gestation, no type of trait was consistently more severely affected in one particular sex, although blood pressure was generally increased in both sexes. Meta-analysis found no difference between sexes in the effect of protein restriction throughout gestation on blood pressure. Among studies restricting food in the latter half of gestation only, there were again few consistent sex-dependent effects, although three studies found blood pressure was increased in males only. Meta-analysis found that food restriction in the second half of gestation increased adult blood pressure in both sexes, with a significantly greater effect in males. Birthweight was consistently reduced in both sexes, a result confirmed by meta-analysis. We found little support for the hypotheses that males are more affected by food and protein restriction, or that effects are particularly severe if nutrition is reduced part-way through gestation. However, less than half of the studies tested for sex by maternal diet interactions to identify sex-dependent effects. As a result, many reported sex-specific effects may be false positives.

中文翻译：

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产前食物和蛋白质限制对大鼠和小鼠后代生理的性别依赖性影响：系统评价和荟萃分析

男性和女性可能会经历早年逆境对终生健康的不同影响。一种假设是，男性胎儿对胎儿生长的投入更多，而对胎盘生长的投入相对较少，这使得他们在子宫内容易受到营养不良的影响，特别是如果在妊娠中途营养减少的话。我们的目标是检查（1）大鼠和小鼠的食物和/或蛋白质限制是否具有一致的性别依赖性影响，（2）性别依赖性在不同类型的结果之间存在差异，以及（3）限制开始时男性受到的影响更严重妊娠的中途。搜索 PubMed 和 Web of Science 以确定符合条件的研究。符合条件的研究描述了在大鼠或小鼠妊娠期间限制蛋白质或食物的对照实验，检查了人工妊娠后代的生理特征，并测试了男性和女性之间的影响是否不同。我们的搜索确定了 292 篇文章，其中 72 篇全文被评估，65 篇被纳入进一步综合。大多数 (50) 使用 Wistar 或 Sprague-Dawley 大鼠，因此这些是主要焦点。在孕期限制母亲饮食的研究中，没有哪一种性状在某一特定性别中受到更严重的影响，尽管两性的血压普遍升高。荟萃分析发现，在整个妊娠期间限制蛋白质对血压的影响没有性别差异。在仅在妊娠后期限制食物的研究中，几乎没有一致的性别依赖性影响，尽管三项研究发现只有男性的血压升高。荟萃分析发现，妊娠后半期的食物限制会增加男女成人的血压，对男性的影响明显更大。荟萃分析证实了这一结果，两性的出生体重均持续降低。我们发现几乎没有证据支持男性更容易受到食物和蛋白质限制的影响，或者如果在妊娠中途减少营养，影响会特别严重。然而，只有不到一半的研究通过母亲的饮食相互作用来测试性别，以确定性别依赖的影响。因此，许多报告的性别特异性影响可能是假阳性。荟萃分析发现，妊娠后半期的食物限制会增加男女成人的血压，对男性的影响明显更大。荟萃分析证实了这一结果，两性的出生体重均持续降低。我们发现几乎没有证据支持男性更容易受到食物和蛋白质限制的影响，或者如果在妊娠中途减少营养，影响会特别严重。然而，只有不到一半的研究通过母亲的饮食相互作用来测试性别，以确定性别依赖的影响。因此，许多报告的性别特异性影响可能是假阳性。荟萃分析发现，妊娠后半期的食物限制会增加男女成人的血压，对男性的影响明显更大。荟萃分析证实了这一结果，两性的出生体重均持续降低。我们发现几乎没有证据支持男性更容易受到食物和蛋白质限制的影响，或者如果在妊娠中途减少营养，影响会特别严重。然而，只有不到一半的研究通过母亲的饮食相互作用来测试性别，以确定性别依赖的影响。因此，许多报告的性别特异性影响可能是假阳性。我们发现几乎没有证据支持男性更容易受到食物和蛋白质限制的影响，或者如果在妊娠中途减少营养，影响会特别严重。然而，只有不到一半的研究通过母亲的饮食相互作用来测试性别，以确定性别依赖的影响。因此，许多报告的性别特异性影响可能是假阳性。我们发现几乎没有证据支持男性更容易受到食物和蛋白质限制的影响，或者如果在妊娠中途减少营养，影响会特别严重。然而，只有不到一半的研究通过母亲的饮食相互作用来测试性别，以确定性别依赖的影响。因此，许多报告的性别特异性影响可能是假阳性。