<i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice

Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of <i>Per1/Per2</i> Double knockout (DKO) reduced the reproductive capacity of elderly male mice....

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Main Authors: Qinrui Liu, Hu Wang, Hualin Wang, Na Li, Ruyi He, Zhiguo Liu
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/13/7399
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author Qinrui Liu
Hu Wang
Hualin Wang
Na Li
Ruyi He
Zhiguo Liu
author_facet Qinrui Liu
Hu Wang
Hualin Wang
Na Li
Ruyi He
Zhiguo Liu
author_sort Qinrui Liu
collection DOAJ
description Circadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of <i>Per1/Per2</i> Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Spermatogenesis genes, <i>Tubd1</i> and <i>Pafah1b</i> were down-regulated, influencing tubulin dynamics and leading to impaired motility. Seleno-compound metabolic loci, <i>Scly</i> and <i>Sephs2</i>, were up-regulated and <i>Slc7a11</i> and <i>Selenop</i> were down-regulated. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Therefore, <i>Per1/Per2</i> disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility.
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spelling doaj.art-0a103a42d1b34f759bceff1ccae0fa8e2023-11-23T20:13:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012313739910.3390/ijms23137399<i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male MiceQinrui Liu0Hu Wang1Hualin Wang2Na Li3Ruyi He4Zhiguo Liu5School of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, ChinaCircadian rhythm disorders caused by genetic or environmental factors lead to decreased male fertility but the mechanisms are poorly understood. The current study reports that the mechanism of <i>Per1/Per2</i> Double knockout (DKO) reduced the reproductive capacity of elderly male mice. The sperm motility and spermatogenic capacity of male DKO mice were weak. Hormone-targeted metabolomics showed reduced plasma levels of free testosterone in DKO male mice compared with WT male mice. Transcriptomic analysis of testicular tissue showed the down-regulation of testosterone synthesis-related enzymes (Cyp11a1, Cyp17a1, Hsd17b3, Hsd3b1, and Star) in the steroid hormone synthesis pathway. Spermatogenesis genes, <i>Tubd1</i> and <i>Pafah1b</i> were down-regulated, influencing tubulin dynamics and leading to impaired motility. Seleno-compound metabolic loci, <i>Scly</i> and <i>Sephs2</i>, were up-regulated and <i>Slc7a11</i> and <i>Selenop</i> were down-regulated. Western-blotting showed that steroid acute regulatory protein (StAR) and p-CREB, PKA and AC1 were reduced in testicular tissue of DKO mice compared to WT. Therefore, <i>Per1/Per2</i> disruption reduced testosterone synthesis and sperm motility by affecting the PKA-StAR pathway, leading to decreased fertility.https://www.mdpi.com/1422-0067/23/13/7399circadian clock<i>Per1/Per2</i>fertilitytestosterone synthesissperm motility
spellingShingle Qinrui Liu
Hu Wang
Hualin Wang
Na Li
Ruyi He
Zhiguo Liu
<i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
International Journal of Molecular Sciences
circadian clock
<i>Per1/Per2</i>
fertility
testosterone synthesis
sperm motility
title <i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
title_full <i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
title_fullStr <i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
title_full_unstemmed <i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
title_short <i>Per1/Per2</i> Disruption Reduces Testosterone Synthesis and Impairs Fertility in Elderly Male Mice
title_sort i per1 per2 i disruption reduces testosterone synthesis and impairs fertility in elderly male mice
topic circadian clock
<i>Per1/Per2</i>
fertility
testosterone synthesis
sperm motility
url https://www.mdpi.com/1422-0067/23/13/7399
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