Laboratorio de Biología de la Reproducción (LABIR), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL-CONICET), Av. Ejército de los Andes 950, D5700HHW, San Luis, Argentina.
Histología, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Av. Ejército de los Andes 950, Bloque I, Piso No. 1, 5700, San Luis, Argentina.
Cell Tissue Res. 2021 May;384(2):487-498. doi: 10.1007/s00441-021-03436-5. Epub 2021 Mar 29.
The GnRH/GnRH receptor system has been found in several extrapituitary tissues, although its physiological significance has not yet been well established. Taking into account that the peripheral neural system can act as a modulator of pregnancy corpus luteum, the objective was to physiologically investigate the presence of the GnRH system in coeliac ganglion (CG) and to analyse its possible involvement in luteal regression through the superior ovarian nerve (SON) at the end of pregnancy in the rat. The integrated ex vivo CG-SON-Ovary system of rats on day 21 of pregnancy was used. Cetrorelix (CTX), a GnRH receptor antagonist, was added into the ganglionic compartment while the control systems were untreated. Ganglionic GnRH release was detected under basal conditions. Then, the CTX addition in CG increased it, which would indicate the blockade of the receptor. In turn, CTX in CG caused an increase in ovarian progesterone release. Furthermore, the luteal cells showed an increase in the expression of Hsd3b1 and a decrease in the expression of Akr1c3 (progesterone synthesis and degradation enzymes, respectively), reduced TUNEL staining according to an increase in the antioxidant defence system activity and low lipid peroxide levels. The ovarian and ganglionic nitric oxide (NO) release increased, while the luteal nitrotyrosine content, measured as nitrosative stress marker, decreased. CTX in CG decreased the ovarian noradrenaline release. The present study provides evidence that GnRH from CG may trigger neuronal signals that promote the luteal regression in late pregnancy by affecting the release of NO and noradrenaline in the ovary.
GnRH/GnRH 受体系统已在几种垂体外组织中发现，尽管其生理意义尚未得到充分确立。考虑到外周神经系统可以作为妊娠黄体的调节剂，本研究旨在从生理学上研究 GnRH 系统在腹腔神经节（CG）中的存在，并分析其通过卵巢上神经（SON）在妊娠末期参与黄体退化的可能性。本研究使用了妊娠第 21 天大鼠的 CG-SON-卵巢体外整合系统。添加 GnRH 受体拮抗剂 cetrorelix（CTX）到神经节腔中，而对照系统则未处理。在基础条件下检测到 CG 中的 GnRH 释放。然后，CG 中的 CTX 增加了 GnRH 的释放，这表明受体被阻断。反过来，CG 中的 CTX 导致卵巢孕激素释放增加。此外，黄体细胞中 Hsd3b1 的表达增加，Akr1c3（孕激素合成和降解酶）的表达减少，根据抗氧化防御系统活性的增加和脂质过氧化物水平的降低，TUNEL 染色减少。卵巢和神经节中的一氧化氮（NO）释放增加，而黄体中硝基酪氨酸含量（作为硝化应激标志物）减少。CG 中的 CTX 减少了卵巢去甲肾上腺素的释放。本研究提供的证据表明，CG 中的 GnRH 可能通过影响卵巢中 NO 和去甲肾上腺素的释放来触发神经元信号，从而促进妊娠晚期的黄体退化。
