Selective autophagy, lipophagy and mitophagy, in the Harderian gland along the oestrous cycle: a potential retrieval effect of melatonin

• Published in: Scientific reports Vol. 9; no. 1; pp. 18597 - 11
• Main Authors: García-Macia, Marina, Santos-Ledo, Adrián, Caballero, Beatriz, Rubio-González, Adrian, de Luxán-Delgado, Beatriz, Potes, Yaiza, Rodríguez-González, Susana Mª., Boga, José Antonio, Coto-Montes, Ana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-12-2019; Nature Publishing Group
• Subjects: 13/51; 14/19; 14/28; 14/63; 631/337/474/1624; 631/443/494; 631/80/39/2346; 631/80/39/2348; 82/1; 82/29; 82/80; Animals; Autophagy; Estrous Cycle; Estrus cycle; Female; Harderian gland; Harderian Gland - metabolism; Harderian Gland - pathology; Homeostasis; Hormones; Humanities and Social Sciences; Inflammation; Lipids - chemistry; Lysosomes - metabolism; Melatonin; Melatonin - metabolism; Mesocricetus; Mitochondria; Mitochondria - metabolism; Mitophagy; multidisciplinary; NF-kappa B - metabolism; NF-κB protein; Oxidative Stress; Phagocytosis; Receptors, Melatonin - metabolism; Science; Science (multidisciplinary); Sequestosome-1 Protein - metabolism; Sex Factors; Sexual dimorphism; Transcription factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-54743-5

Sexual dimorphism has been reported in many processes. However, sexual bias in favour of the use of males is very present in science. One of the main reasons is that the impact of hormones in diverse pathways and processes such as autophagy have not been properly addressed
in vivo
. The Harderian gland is a perfect model to study autophagic modulation as it exhibits important changes during the oestrous cycle. The aim of this study is to identify the main processes behind Harderian gland differences under oestrous cycle and their modulator. In the present study we show that redox-sensitive transcription factors have an essential role: NF-κB may activate SQSTM1/p62 in oestrus, promoting selective types of autophagy: mitophagy and lipophagy. Nrf2 activation in dioestrus, leads the retrieval phase and restoration of mitochondrial homeostasis. Melatonin’s receptors show higher expression in dioestrus, leading to decreases in pro-inflammatory mediators and enhanced Nrf2 expression. Consequently, autophagy is blocked, and porphyrin release is reduced. All these results point to melatonin as one of the main modulators of the changes in autophagy during the oestrous cycle.