<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....
Main Authors: | , , , , , |
---|---|
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 |
_version_ | 1797479489695907840 |
---|---|
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. |
first_indexed | 2024-03-09T21:46:59Z |
format | Article |
id | doaj.art-0a103a42d1b34f759bceff1ccae0fa8e |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-09T21:46:59Z |
publishDate | 2022-07-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT qinruiliu iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice AT huwang iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice AT hualinwang iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice AT nali iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice AT ruyihe iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice AT zhiguoliu iper1per2idisruptionreducestestosteronesynthesisandimpairsfertilityinelderlymalemice |