4.6 Article

Prolonged melatonin treatment promote testicular recovery by enhancing RAC1-mediated apoptotic cell clearance and cell junction-dependent spermatogensis after heat stress

Journal

THERIOGENOLOGY
Volume 162, Issue -, Pages 22-31

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.theriogenology.2020.12.015

Keywords

Male infertility; Melatonin; Heat stress; Sertoli cell; Phagocytosis

Funding

  1. National Key Research and Development Program of China [2016YFD0500506]
  2. China Agriculture Research System [CARS-43-D-1]

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The study found that melatonin can accelerate germ cell apoptosis, spermatogenic cell regeneration, and testicular weight recovery, by enhancing the phagocytotic activity of Sertoli cells and promoting spermatogenic cell regeneration to accelerate testicular recovery after heat stress.
Introduction: A decline in semen quality caused by global warming and torrid working conditions is a major cause of human male infertility, and heat stress-induced decreases in male reproductive ability results in economic losses in livestock husbandry. Increasing evidence suggests that melatonin exerts protective effects on stress-induced DNA damage and apoptosis in germ cells. However, few studies have assessed the effects of melatonin on testicular recovery during post-heat stress and the underlying mechanisms. Methods and results: In vivo studies using 8-week-old male CD-1 mice revealed that melatonin pretreatment (50 mg/kg for 5 days) did not alleviate heat stress-induced germ cell loss and disrupted testicular histomorphology, however, long-term melatonin administration after heat stress accelerated germ cell apoptosis, spermatogenic cell regeneration, and testicular weight recovery. In vitro studies demonstrated that melatonin enhanced RAC1 activity, resulting in increased phagocytosis of apoptotic germ cells by Sertoli cells. In addition, melatonin restored gap junctions and tight junctions after heat stress, thereby promoting hollow seminiferous tubule filling. Discussion: Long-term melatonin administration accelerated testicular recovery after heat stress by enhancing the phagocytotic activity of Sertoli cells and the regeneration of spermatogenic cells. This finding suggests that melatonin is a potential therapeutic for heat stress-induced male infertility. (c) 2020 Elsevier Inc. All rights reserved.

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