Age-related changes in gene expression patterns of immature and aged rat primordial follicles

ABSTRACT

Women are born with millions of primordial follicles which gradually decrease with increasing age and this irreversible supply of follicles completely exhausts at menopause. The fertility capacity of women diminishes in parallel with aging. The mechanisms for reproductive aging are not fully understood. We have observed a decline in Brca1 mediated DNA repair in aging rat primordial follicles. To further understand the age-related molecular changes, we performed microarray gene expression analysis using total RNA extracted from immature (18 to 20 day old) and aged (400 to 450 day old) rat primordial follicles. The results of current microarray study revealed that there were 1,011 (>1.5 fold, p<0.05) genes differentially expressed between two groups in which 422 genes were up-regulated and 589 genes were down-regulated in aged rat primordial follicles compared to immature primordial follicles. The gene ontology and pathway analysis of differentially expressed genes revealed a critical biological function such as cell cycle, oocyte meiosis, chromosomal stability, transcriptional activity, DNA replication, and DNA repair were affected by age. This considerable difference in gene expression profiles may have an adverse influence on oocyte quality. Our data provide information on the processes that may contribute to aging and age-related decline in fertility.

KEYWORDS:

• Aging
• gene expression
• oocytes
• rat primordial follicles

Acknowledgments

AJR wishes to thank the Indian National Science Academy (INSA) for the award of INSA Honorary Scientist Fellowship and also the Department of Biochemistry, Indian Institute of Science (IISc), Bangalore, India. The authors would like to thank the Department of Biotechnology, Government of India (Grant Number: BT/PR5487/AAQ/1/500/2012) for financial support provided during the course of the work.

Declaration of interest

Department of Biotechnology, Government of India (Grant Number: BT/PR5487/AAQ/1/500/2012). The authors report no conflicts of interest.

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Notes on contributors

Vijayakumar Govindaraj

Designed the study, performed the experiments, analyzed the data, and wrote the paper: VG; Microarray data analysis: PC, MV, VG; Performed PCR validation of microarray data: VG, HK; Conception and design of research study and critical review of the manuscript: AJR.

Harshini Krishnagiri

Designed the study, performed the experiments, analyzed the data, and wrote the paper: VG; Microarray data analysis: PC, MV, VG; Performed PCR validation of microarray data: VG, HK; Conception and design of research study and critical review of the manuscript: AJR.

Payal Chakraborty

Designed the study, performed the experiments, analyzed the data, and wrote the paper: VG; Microarray data analysis: PC, MV, VG; Performed PCR validation of microarray data: VG, HK; Conception and design of research study and critical review of the manuscript: AJR.

Madavan Vasudevan

Designed the study, performed the experiments, analyzed the data, and wrote the paper: VG; Microarray data analysis: PC, MV, VG; Performed PCR validation of microarray data: VG, HK; Conception and design of research study and critical review of the manuscript: AJR.

A. Jagannadha Rao

Designed the study, performed the experiments, analyzed the data, and wrote the paper: VG; Microarray data analysis: PC, MV, VG; Performed PCR validation of microarray data: VG, HK; Conception and design of research study and critical review of the manuscript: AJR.