Female reproductive aging is master-planned at the level of ovary.

Sayani Banerjee,Ghungroo Saraswat,Sutapa Banerjee,Syed N Kabir,Soma Aditya Bandyopadhyay,Stephen Franks

doi:10.1371/journal.pone.0096210

Sayani Banerjee, Ghungroo Saraswat + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0096210

Copy DOI

Journal: PloS one	Publication Date: May 2, 2014
Citations: 35	License type: CC BY 4.0

Affiliation: Indian Institute of Chemical Biology

Abstract

The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final phase of ovarian life when the follicle reserve wanes below certain threshold size.

Highlights

The ovary, an ever-changing tissue and dynamic multicompartmental organ, is unique in the endocrine system in that in every reproductive cycle it develops entirely new secretory structures, the graafian follicles, from a pool of primordial follicles [1]
The relationship between follicle number and the menopausal transition has not been explicitly studied; using mathematical model it has been demonstrated that follicular reserve declines at an exponential rate that gradually changes throughout life leading to accelerated rate of atresia during the years preceding menopause [7,8,9,10]
While working on a rodent model of primary ovarian insufficiency (POI), we surprisingly noted that experimentally developed ovary with deficient follicular pool, like that of premenopausal ovaries, experiences increased rate of atresia of the remaining follicular pool

Summary

Introduction

The ovary, an ever-changing tissue and dynamic multicompartmental organ, is unique in the endocrine system in that in every reproductive cycle it develops entirely new secretory structures, the graafian follicles, from a pool of primordial follicles [1]. The primordial follicles are the major endocrine and reproductive units of the ovary whose numbers determine both reproductive potential and reproductive life span [2]. Follicular atresia, continues through the course of reproductive life until the reserve is exhausted at menopause. Except for a tiny number of follicles that are expended between puberty and menopause in the form of ovulation, atresia remains the major form of follicular expenditure. The relationship between follicle number and the menopausal transition has not been explicitly studied; using mathematical model it has been demonstrated that follicular reserve declines at an exponential rate that gradually changes throughout life leading to accelerated rate of atresia during the years preceding menopause [7,8,9,10]. The question remains: what are the governing factors that accelerate the rate of atresia during the menopausal ages? Is it the chronological age; or the ovarian aging impacts the process?

Methods

Results

Conclusion