Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge, UK.
Biol Reprod. 2021 Apr 1;104(4):745-770. doi: 10.1093/biolre/ioaa232.
Exposures to adverse conditions in utero can lead to permanent changes in the structure and function of key physiological systems in the developing fetus, increasing the risk of disease and premature aging in later postnatal life. When considering the systems that could be affected by an adverse gestational environment, the reproductive system of developing female offspring may be particularly important, as changes have the potential to alter both reproductive capacity of the first generation, as well as health of the second generation through changes in the oocyte. The aim of this review is to examine the impact of different adverse intrauterine conditions on the reproductive system of the female offspring. It focuses on the effects of exposure to maternal undernutrition, overnutrition/obesity, hypoxia, smoking, steroid excess, endocrine-disrupting chemicals, and pollutants during gestation and draws on data from human and animal studies to illuminate underlying mechanisms. The available data indeed indicate that adverse gestational environments alter the reproductive physiology of female offspring with consequences for future reproductive capacity. These alterations are mediated via programmed changes in the hypothalamic-pituitary-gonadal axis and the structure and function of reproductive tissues, particularly the ovaries. Reproductive programming may be observed as a change in the timing of puberty onset and menopause/reproductive decline, altered menstrual/estrous cycles, polycystic ovaries, and elevated risk of reproductive tissue cancers. These reproductive outcomes can affect the fertility and fecundity of the female offspring; however, further work is needed to better define the possible impact of these programmed changes on subsequent generations.
子宫内不利环境的暴露可导致发育中胎儿的关键生理系统的结构和功能发生永久性变化，增加了在出生后生命后期患病和过早衰老的风险。在考虑可能受到不利妊娠环境影响的系统时，发育中雌性后代的生殖系统可能尤为重要，因为这些变化有可能通过卵母细胞的改变来改变第一代的生殖能力以及第二代的健康。本综述的目的是检查不同不利宫内条件对雌性后代生殖系统的影响。它侧重于研究母体营养不良、营养过剩/肥胖、缺氧、吸烟、类固醇过量、内分泌干扰化学物质和污染物暴露于妊娠期对雌性后代生殖系统的影响，并利用来自人类和动物研究的数据阐明潜在机制。现有数据确实表明，不利的宫内环境改变了雌性后代的生殖生理，从而影响了未来的生殖能力。这些改变是通过下丘脑-垂体-性腺轴以及生殖组织的结构和功能的程序性改变介导的，特别是卵巢。生殖编程可能表现为青春期起始和绝经/生殖衰退时间的改变、月经/发情周期改变、多囊卵巢和生殖组织癌症风险增加。这些生殖结果会影响雌性后代的生育能力和繁殖能力；然而，需要进一步的工作来更好地定义这些程序性改变对后代的可能影响。
