Maternal nutrient restriction impairs young adult offspring ovarian signaling resulting in reproductive dysfunction and follicle loss†
Maternal nutrient restriction impairs young adult offspring ovarian signaling resulting in reproductive dysfunction and follicle loss†
复制标题
母体营养限制会损害成年早期子代的卵巢信号传导，进而导致生殖功能障碍和卵泡丢失† 注释：“†”这个符号在原文可能有特定注释含义，一般直接保留。
DOI：
10.1093/biolre/ioy008
复制
发表时间：
2018-05
影响因子：
3.6
通讯作者：
Kaitlyn A. Chan;Patrycja A. Jazwiec;W. Gohir;J. Petrik;D. Sloboda
中科院分区：
文献类型：
--
作者：
Kaitlyn A. Chan;Patrycja A. Jazwiec;W. Gohir;J. Petrik;D. Sloboda
摘要生殖异常被认为是产前营养不良的后代的健康并发症。我们之前已经在啮齿动物模型中表明，怀孕期间营养限制出生的后代出生时很小，进入青春期早，并显示出成年后卵巢早期衰老的特征。本研究探讨了参与卵泡募集和生长的关键蛋白是否介导卵泡丢失。将妊娠大鼠在整个妊娠期和哺乳期随机分配至标准饮食（CON），或在妊娠期间进行热量限制（对照组的50%）饮食（UN）。在出生后第4、27和65天研究后代的生殖表型。母体UN导致年轻成人（P65）不规则的发情周期，由于持续发情，有腔卵泡，黄体的显着损失，闭锁卵泡的增加。UN后代中生长卵泡的减少似乎是由于年轻成年后代卵巢中促凋亡因子CASP 3（caspase 3）的免疫阳性染色所见的细胞凋亡增加。UN青春期前的后代有腔卵泡中Fshr的表达水平降低，这可能有助于PI 3 K/AKT活化的降低，明显表现为青春期前有腔卵泡中pAKT免疫定位的降低。此外，UN后代的新生儿卵巢显示AMHR 2（抗苗勒管激素受体2）免疫阳性染色水平降低。总的来说，这些数据表明，母亲在怀孕期间的联合国影响卵巢功能的后代早在P65，并提供了一个模型，以了解驱动早期生活联合国诱导的卵泡损失和生殖功能障碍的机制。生命早期营养限制导致胎儿生长受限、生命早期卵泡丢失、生殖周期不规则，这些都是由控制新生儿后代卵巢中原始卵泡募集的关键因素受损所支持的。
Abstract Reproductive abnormalities are included as health complications in offspring exposed to poor prenatal nutrition. We have previously shown in a rodent model that offspring born to nutrient restriction during pregnancy are born small, enter puberty early, and display characteristics of early ovarian aging as adults. The present study investigated whether key proteins involved in follicle recruitment and growth mediate ovarian follicle loss. Pregnant rats were randomized to a standard diet throughout pregnancy and lactation (CON), or a calorie-restricted (50% of control) diet (UN) during pregnancy. Offspring reproductive phenotype was investigated at postnatal days 4, 27, and 65. Maternal UN resulted in young adult (P65) irregular estrous cyclicity due to persistent estrus, a significant loss of antral follicles, corpora lutea, and an increase in atretic follicles. This decrease in growing follicles in UN offspring appears to be due to increased apoptosis as seen by immunopositive staining of pro-apoptotic factor CASP3 (caspase 3) in ovaries of young adult offspring. UN prepubertal offspring had reduced expression levels of Fshr in antral follicles, which may contribute to a decrease in PI3K/AKT activation evident as a decrease in pAKT immunolocalization in prepubertal antral follicles. Moreover, neonatal ovaries of UN offspring show decreased levels of immunopositive staining for AMHR2 (anti-mullerian hormone receptor 2). Collectively, these data demonstrate that maternal UN during pregnancy impacts ovarian function in offspring as early as P65 and provides a model for understanding the mechanisms driving early life UN-induced follicle loss and reproductive dysfunction. Summary Sentence Early life nutrient restriction induces fetal growth restriction, early life follicle loss, reproductive cycle irregularity underpinned by impairments in key factors that control primordial follicle recruitment in neonatal offspring ovaries.