Research Paper Volume 12, Issue 18 pp 18251—18273

Transcriptomic analysis reveals gender differences in gene expression profiling of the hypothalamus of rhesus macaque with aging

Yong Fan1, *, , Congru Li2, *, , Wendi Pei2, *, , Tao Tan3, , Rong Li2, , Jie Qiao2, , Yang Yu2,4, ,

  • 1 Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
  • 2 Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University Third Hospital, Beijing 100191, China
  • 3 Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China
  • 4 Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China
* Equal contribution

Received: April 9, 2020       Accepted: June 29, 2020       Published: September 27, 2020
How to Cite

Copyright: © 2020 Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Due to the current delay in childbearing, the importance of elucidating the underlying mechanisms for reproductive aging has increased. Human fertility is considered to be controlled by hormones secreted by the hypothalamic-pituitary-gonadal axis. To clarify the changes in hypothalamic gene expression with increasing age, we performed paired-end strand-specific total RNA sequencing for the hypothalamus tissues of rhesus. We found that hypothalamic gene expression in females was more susceptible to aging than that in males, and reproductive aging in females and males might have different regulatory mechanisms. Intriguingly, the expression of most of the hormones secreted by hypothalamus showed no significant difference among the macaques grouped by age and gender. Moreover, the age-related housekeeping genes in females were enriched in neurodegenerative disorders- and metabolic-related pathways. This study provides evidence that aging may influence hypothalamic gene expression through different mechanisms in females and males and may involve some nonhormonal pathways, which helps further elucidate the process of reproductive aging and improve clinical fertility assessment in mid-aged women.


HPG: hypothalamic-pituitary-gonadal; GnRH: gonado-tropin-releasing hormone; FSH: follicle stimulating hormone; LH: luteinizing hormone; KEGG: Kyoto Encyclopedia of Genes and Genomes; AD: Alzheimer’s disease; ALS: amyotrophic lateral sclerosis; GO: Gene Ontology; CRH: corticotropin releasing hormone; SST: somatostatin; TRH: thyrotropin-releasing hormone; AVP: arginine vasopressin; OXT: oxytocin; CNS: central nervous system; ROS: reactive oxygen species; IKK-b: IkB kinase-b; NF-kB: nuclear factor kB; DAVID: Database for Annotation: Visualization and Integrated Discovery; CPAT: Coding Potential Assessment Tool; CPC2: Coding Potential Calculator.