Departments of Obstetrics, Gynecology, and Reproductive Sciences (S.K.F., A.D., R.K.S., W.L., X.L., P.F.R.) and Pediatrics (E.M.), University of California San Francisco, San Francisco, California 94143.
Endocrinology. 2014 Nov;155(11):4554-67. doi: 10.1210/en.2014-1465. Epub 2014 Sep 11.
The preimplantation embryo is particularly vulnerable to environmental perturbation, such that nutritional and in vitro stresses restricted exclusively to this stage may alter growth and affect long-term metabolic health. This is particularly relevant to the over 5 million children conceived by in vitro fertilization (IVF). We previously reported that even optimized IVF conditions reprogram mouse postnatal growth, fat deposition, and glucose homeostasis in a sexually dimorphic fashion. To more clearly interrogate the metabolic changes associated with IVF in adulthood, we used nontargeted mass spectrometry to globally profile adult IVF- and in vivo-conceived liver and gonadal adipose tissues. There was a sex- and tissue-specific effect of IVF on adult metabolite signatures indicative of metabolic reprogramming and oxidative stress and reflective of the observed phenotypes. Additionally, we observed a striking effect of IVF on adult sexual dimorphism. Male-female differences in metabolite concentration were exaggerated in hepatic IVF tissue and significantly reduced in IVF adipose tissue, with the majority of changes affecting amino acid and lipid metabolites. We also observed female-specific changes in markers of oxidative stress and adipogenesis, including reduced glutathione, cysteine glutathione disulfide, ophthalmate, urate, and corticosterone. In summary, embryo manipulation and early developmental experiences can affect adult patterns of sexual dimorphism and metabolic physiology.
胚胎植入前阶段特别容易受到环境干扰，因此仅发生在此阶段的营养和体外应激可能会改变生长过程，并影响长期代谢健康。这对于通过体外受精（IVF）孕育的 500 多万儿童来说尤为重要。我们之前的报告表明，即使优化了 IVF 条件，也会以性别二态的方式重新编程小鼠的出生后生长、脂肪沉积和葡萄糖稳态。为了更清楚地研究与成年 IVF 相关的代谢变化，我们使用非靶向质谱法对成年 IVF 和体内受精的肝脏和性腺脂肪组织进行了全面分析。IVF 对成年代谢物特征具有性别和组织特异性的影响，这些特征表明存在代谢重编程和氧化应激，反映了所观察到的表型。此外，我们还观察到 IVF 对成年性别二态性的显著影响。IVF 肝组织中雄性和雌性之间的代谢物浓度差异明显扩大，而 IVF 脂肪组织中的差异则显著缩小，大多数变化都影响了氨基酸和脂质代谢物。我们还观察到了与氧化应激和脂肪生成相关的雌性特异性标志物的变化，包括还原型谷胱甘肽、半胱氨酸谷胱甘肽二硫化物、眼氨酸、尿酸和皮质酮。总之，胚胎操作和早期发育经历可能会影响成年性别二态性和代谢生理学模式。
