Abstract

Here, we study possible mechanisms of (in/sub)fertility related to the acute or repeated psychological stresses (the most common stresses in human society) by following the transcriptional profile of 22 mitochondrial dynamics/function markers and 22 signaling molecules regulating both mitochondrial dynamics and spermatozoa number/functionality. An in vivo study mimicking acute (once for 3 h) and repeated (3 h for 10 consecutive days) psychophysical stress was performed on adult rats. The analysis of hormones, the number/functionality of spermatozoa, and 44 transcriptional markers were performed on individual samples from up to 12 animals per group. Results showed that both types of stress reduced spermatozoa functionality (acute by 4.4-fold, repeated by 3.3-fold) and ATP production (acute by 2.3-fold, repeated by 14.5-fold), while only repeated stress reduces the number of spermatozoa (1.9-fold). Stress significantly disturbed transcription of 34-out-of-44 markers (77%). Mitochondrial dynamics and functionality markers: 18-out-of-22 =>82% (mitochondrial-biogenesis-markers –>6-out-of-8 =>75%; mitochondrial-fusion-markers –>3-out-of-3 =>100%; mitochondrial-fission-markers –>1-out-of-2 =>50%; mitochondrial-autophagy-markers –>3-out-of-3 =>100%; mitochondrial-functionality-markers –>5-out-of-6 =>83%). Markers of signaling pathways regulating both mitochondrial dynamics/functionality and spermatozoa number/functionality important for male (in/sub)fertility –>16-out-of-22 =>73% (cAMP-signaling-markers –>8-out-of-12 =>67%; MAPK-signaling-markers –>8-out-of-10 =>80%). Accordingly, stress-triggered changes of transcriptional profile of mitochondrial dynamics/functionality markers as well as signaling molecules regulating both mitochondrial dynamics and spermatozoa number and functionality represent adaptive mechanisms.

Highlights

  • The miracle of life starts with fertilization and requires perfect spermatozoa functionality, which is a highly energy driven and demanding process regulated by complex as well as a wide network of signaling pathways

  • A higher number of stressful life events are observed in infertile men, and this was associated with a decline in semen quality during fertility treatment [3]

  • For the first time our results show that stress triggers changes of transcriptional profile of mitochondrial dynamics and functionality markers as well as signaling molecules (Figure 4) regulating both mitochondrial dynamics and spermatozoa number and functionality

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Summary

Introduction

The miracle of life starts with fertilization and requires perfect spermatozoa functionality, which is a highly energy driven and demanding process regulated by complex as well as a wide network of signaling pathways. Many studies showed the increase of unexplained cases of infertile young males and decrease of the fertility rate in men younger than age 30. This is important, since the semen quality and male fertility are important as the fundamental marker of reproductive health and the fundamental biomarker of overall health [1,2]. As well as major stressful life events, have been linked to reduced male reproductive function [3,13,14]. A higher number of stressful life events are observed in infertile men, and this was associated with a decline in semen quality during fertility treatment [3]. Epidemiological studies showed that DNA damage during stress-response is regulated through β2-adrenergic-receptors [15], strongly suggesting the importance of stress-signaling in regulation of mitochondrial homeostasis

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