Minabe Shiori, Iwata Kinuyo, Watanabe Youki, Ishii Hirotaka, Ozawa Hitoshi
Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Yahaba, Japan.
Endocr Connect. 2022 Dec 15;12(1). doi: 10.1530/EC-22-0307. Print 2023 Jan 1.
The nutritional environment during development periods induces metabolic programming, leading to metabolic disorders and detrimental influences on human reproductive health. This study aimed to determine the long-term adverse effect of intrauterine malnutrition on the reproductive center kisspeptin-neurokinin B-dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) of female offspring. Twelve pregnant rats were divided into ad-lib-fed (control, n = 6) and 50% undernutrition (UN, n = 6) groups. The UN group was restricted to 50% daily food intake of the control dams from gestation day 9 until term delivery. Differences between the two groups in terms of various maternal parameters, including body weight (BW), pregnancy duration, and litter size, as well as birth weight, puberty onset, estrous cyclicity, pulsatile luteinizing hormone (LH) secretion, and hypothalamic gene expression of offspring, were determined. Female offspring of UN dams exhibited low BW from birth to 3 weeks, whereas UN offspring showed signs of precocious puberty; hypothalamic Tac3 (a neurokinin B gene) expression was increased in prepubertal UN offspring, and the BW at the virginal opening was lower in UN offspring than that in the control group. Interestingly, the UN offspring showed significant decreases in the number of KNDy gene-expressing cells after 29 weeks of age, but the number of ARC kisspeptin-immunoreactive cells, pulsatile LH secretions, and estrous cyclicity were comparable between the groups. In conclusion, intrauterine undernutrition induced various changes in KNDy gene expression depending on the life stage. Thus, intrauterine undernutrition affected hypothalamic developmental programming in female rats.
发育时期的营养环境会引发代谢编程，导致代谢紊乱，并对人类生殖健康产生不利影响。本研究旨在确定子宫内营养不良对雌性后代下丘脑弓状核（ARC）中生殖中枢促性腺激素释放激素神经元（KNDy）的长期不良影响。将12只怀孕大鼠分为自由采食组（对照组，n = 6）和50%营养不足组（UN组，n = 6）。UN组从妊娠第9天到足月分娩，每日食物摄入量限制为对照母鼠的50%。测定了两组在各种母体参数方面的差异，包括体重（BW）、妊娠期和窝仔数，以及后代的出生体重、青春期开始时间、发情周期、促黄体生成素（LH）脉冲分泌和下丘脑基因表达。UN组母鼠的雌性后代从出生到3周龄体重较低，而UN组后代出现性早熟迹象；青春期前UN组后代下丘脑Tac3（一种神经激肽B基因）表达增加，且UN组后代阴道口处的体重低于对照组。有趣的是，UN组后代在29周龄后，表达KNDy基因的细胞数量显著减少，但两组间ARC中促性腺激素释放激素免疫反应性细胞数量、LH脉冲分泌和发情周期相当。总之，子宫内营养不良根据生命阶段诱导了KNDy基因表达的各种变化。因此，子宫内营养不良影响了雌性大鼠下丘脑的发育编程。
