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Neuromodulatory effect of GnRH from coeliac ganglion on luteal regression in the late pregnant rat

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Abstract

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.

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Acknowledgements

We gratefully thank Dario Ramirez PhD for providing anti-nitrotyrosine and Gustavo Cramero, Director of Laboratorio de Análisis Clínicos (LAC, Tunuyán, Mendoza) for his advice in catecholamines determination. We also thank graphic designer Damian Garay for his assistance in the edition of the figure artwork. This work is part of the Doctoral Scholarship-CONICET and Doctoral thesis of Laura Morales.

Funding

This work was supported by Grant PROICO 2-2916-UNSL.

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Author notes

  1. Laura Morales and Sandra Vallcaneras are both co-first authors

Authors and Affiliations

  1. 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

    Laura Morales, Sandra Vallcaneras, María Belén Delsouc & Marilina Casais

  2. 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

    Verónica Filippa & Claudia Aguilera-Merlo

  3. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 5700, San Luis, Argentina

    Verónica Filippa

  4. Instituto de Biología y Medicina Experimental (IBYME-CONICET), V. de Obligado 2490, C1428ADN, Buenos Aires, Argentina

    Marina Fernández

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  1. Laura Morales
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  2. Sandra Vallcaneras
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  3. María Belén Delsouc
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Correspondence to Marilina Casais.

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Animals were handled according to the procedures approved in the UFAW Handbook on the Care and Management of Laboratory Animals. The experimental protocol was approved by the University of San Luis Animal Care and Use Committee (number protocol: B-264/17).

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Morales, L., Vallcaneras, S., Delsouc, M.B. et al. Neuromodulatory effect of GnRH from coeliac ganglion on luteal regression in the late pregnant rat. Cell Tissue Res 384, 487–498 (2021). https://doi.org/10.1007/s00441-021-03436-5

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