Chalmey Clémentine, Giton Frank, Chalmel Frédéric, Fiet Jean, Jégou Bernard, Mazaud-Guittot Séverine
Institut National de la Santé et de la Recherche Médicale, Unité 1085 Institut de Recherche en Santé Environnement et Travail, Institut Fédératif de Recherche 140, Université de Rennes 1, Rennes, France.
Institut National de la Santé et de la Recherche Médicale, U955 Équipe 07, Créteil, France.
PLoS One. 2013 Dec 16;8(12):e82175. doi: 10.1371/journal.pone.0082175. eCollection 2013.
The formation of ovarian follicles is a finely tuned process that takes place within a narrow time-window in rodents. Multiple factors and pathways have been proposed to contribute to the mechanisms triggering this process but the role of endocrine factors, especially estrogens, remains elusive. It is currently hypothesized that removal from the maternal hormonal environment permits follicle formation at birth. However, experimentally-induced maintenance of high 17β-estradiol (E2) levels leads to subtle, distinct, immediate effects on follicle formation and oocyte survival depending on the species and dose. In this study, we examined the immediate effects of neonatal E2 exposure from post-natal day (PND) 0 to PND2 on the whole organism and on ovarian follicle formation in rats. Measurements of plasma E2, estrone and their sulfate conjugates after E2 exposure showed that neonatal female rats rapidly acquire the capability to metabolize and clear excessive E2 levels. Concomitant modifications to the mRNA content of genes encoding selected E2 metabolism enzymes in the liver and the ovary in response to E2 exposure indicate that E2 may modify the neonatal maturation of these organs. In the liver, E2 treatment was associated with lower acquisition of the capability to metabolize E2. In the ovary, E2 depleted the oocyte pool in a dose dependent manner by PND3. In 10 µg/day E2-treated ovaries, apoptotic oocytes were observed in newly formed follicles in addition to areas of ovarian cord remodeling. At PND6, follicles without any visible oocyte were present and multi-oocyte follicles were not observed. Our study reveals a major species-difference. Indeed, neonatal exposure to E2 depletes the oocyte pool in the rat ovary, whereas in the mouse it is well known to increase oocyte survival.
卵巢卵泡的形成是一个精细调节的过程，在啮齿动物的狭窄时间窗口内发生。已经提出多种因素和途径有助于触发这一过程的机制，但内分泌因素，尤其是雌激素的作用仍然难以捉摸。目前推测，脱离母体激素环境可使出生时卵泡形成。然而，实验诱导维持高17β-雌二醇（E2）水平会根据物种和剂量对卵泡形成和卵母细胞存活产生微妙、独特的即时影响。在本研究中，我们研究了从出生后第0天（PND）到PND2新生大鼠暴露于E2对整个机体和卵巢卵泡形成的即时影响。E2暴露后血浆E2、雌酮及其硫酸酯结合物的测量结果表明，新生雌性大鼠迅速获得代谢和清除过量E2水平的能力。伴随E2暴露，肝脏和卵巢中编码所选E2代谢酶的基因mRNA含量发生变化，表明E2可能会改变这些器官的新生成熟过程。在肝脏中，E2处理与代谢E2能力的较低获得有关。在卵巢中，E2在PND3时以剂量依赖方式耗尽卵母细胞库。在每天10μg E2处理的卵巢中，除了卵巢索重塑区域外，在新形成的卵泡中观察到凋亡的卵母细胞。在PND6时，存在没有任何可见卵母细胞的卵泡，未观察到多卵母细胞卵泡。我们的研究揭示了一个主要的物种差异。事实上，新生大鼠暴露于E2会耗尽卵巢中的卵母细胞库，而在小鼠中，众所周知这会增加卵母细胞存活。
