Female reproductive decline is determined by remaining ovarian reserve and age.

Pawel Wilkosz,Gareth D Greggains,Peter Fedorcsak,Tom G Tanbo,Stefan Schlatt

doi:10.1371/journal.pone.0108343

Pawel Wilkosz, Gareth D Greggains + Show 3 more

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https://doi.org/10.1371/journal.pone.0108343

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Journal: PloS one	Publication Date: Oct 13, 2014
Citations: 77	License type: CC BY 4.0

Affiliation: Oslo University Hospital, University of Oslo

Abstract

The early decline and loss of female fertility in humans and other species represents an evolutionary paradox. Despite being born with a vast stock of oocytes, females encounter an exhaustion of ovarian reserve and sterility half way through their natural lives. Female reproductive ageing has been proposed to proceed as an ongoing decline in ovarian reserve, determined by remaining ovarian follicle number. However, despite extensive modelling, the respective contributions of intra-, inter-, and extra-ovarian signalling have not been fully characterised. It remains unclear whether reproductive ageing progresses simply as a pre-determined function of remaining ovarian follicles, or as an age-dependent process in humans. Here, we have analysed ovarian response to hormonal stimulation in women who have undergone surgical removal of a single ovary, in order to investigate the relative contributions of intra-, inter, and extra-ovarian signalling on reproductive ageing. Our data show that in unilaterally oophorectomised women, ovarian response to follicle stimulating hormone (FSH) declines beyond levels predicted by a total ovarian follicle pool model of reproductive ageing. Maintenance of ovarian function later in reproductive life, despite the removal of half of the total ovarian reserve, suggests a role for an extra-ovarian age-dependent regulation of reproductive decline. This highlights the need for further work to identify signalling factors that communicate age-related signals between the soma and the germline.

Highlights

Women are born with a finite stock of approximately 500 000–1 000 000 follicle-enclosed oocytes, which are depleted over the course of their lives [1,2,3,4,5]
It has been documented that endometriomas and peritoneal endometriosis might reduce ovarian reserve followed by decreased ovarian response during IVF treatment [20,21,22], we found no differences in median ovarian response during the first cycle and median age between women with or without endometriosis in the unilateral oophorectomized group (2.33 vs 2.78 and 33.3 vs 33.7 years, respectively)
The data presented here are in opposition to a total ovarian follicle pool model of reproductive ageing that includes both intraand inter-ovarian signalling, without any extra-ovarian agedependent signalling

Summary

Introduction

Women are born with a finite stock of approximately 500 000–1 000 000 follicle-enclosed oocytes, which are depleted over the course of their lives [1,2,3,4,5]. Decline in the ovarian follicle pool, defined at any time as the remaining cohort of ovarian follicles, is associated with reduced fertility in the mid-thirties, irregular menstruation from the midforties, and follicle exhaustion and menopause in the early fifties [7,8]. This process represents one of the earliest organ failures in natural female ageing and raises intriguing questions regarding the relationship between reproductive and organismal ageing [9]. A monthly selection process by FSH gives rise to a single dominant follicle, which is ovulated during the same cycle [6]

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