Dietary lipid and cholesterol induce ovarian dysfunction and abnormal LH response to stimulation in rabbits.

Anne-Gaël Cordier,Thibaut Larcher,Charlotte Dupont,Béatrice Mandon-Pepin,Olivier Picone,Pascale Chavatte-Palmer,Anne Tarrade,Rachel Lévy,Pauline Léveillé,Elodie Poumerol,Michèle Dahirel

doi:10.1371/journal.pone.0063101

Abstract

Background/AimExcess of fat intake is dramatically increasing in women of childbearing age and results in numerous health complications, including reproductive disorders. Using rabbit does as a biomedical model, the aim of this study was to evaluate onset of puberty, endocrine responses to stimulation and ovarian follicular maturation in females fed a high fat high cholesterol diet (HH diet) from 10 weeks of age (i.e., 2 weeks before normal onset of puberty) or a control diet (C diet).Methodology/Principal FindingsThree experiments were performed, each including 8 treated (HH group) and 8 control (C group) does. In experiment 1, the endocrine response to Gonadotropin releasing hormone (GnRH) was evaluated at 13, 18 and 22 weeks of age. In experiment 2, the follicular population was counted in ovaries of adult females (18 weeks of age). In experiment 3, the LH response to mating and steroid profiles throughout gestation were evaluated at 18 weeks of age. Fetal growth was monitored by ultrasound and offspring birth weight was recorded. Data showed a significantly higher Luteinizing hormone (LH) response after induction of ovulation at 13 weeks of age in the HH group. There was no difference at 18 weeks, but at 22 weeks, the LH response to GnRH was significantly reduced in the HH group. The number of atretic follicles was significantly increased and the number of antral follicles significantly reduced in HH does vs. controls. During gestation, the HH diet induced intra-uterine growth retardation (IUGR).ConclusionThe HH diet administered from before puberty onwards affected onset of puberty, follicular growth, hormonal responses to breeding and GnRH stimulation in relation to age and lead to fetal IUGR.

Highlights

Adult lifestyle - generally diet and sedentary habits – as well as environmental chemicals are known factors impacting the fertility of men and women
The objective of this work was to explore the effects of a high fat, high cholesterol diet administered from the prepubertal period on the onset of reproductive function, endocrine status and follicular growth, using a previously established rabbit model [27]
At 13 weeks, the peak Luteinizing hormone (LH) concentrations in response to Gonadotropin releasing hormone (GnRH) was significantly higher in HH does (P,0.02)

Summary

Introduction

Adult lifestyle - generally diet and sedentary habits – as well as environmental chemicals are known factors impacting the fertility of men and women. According to the recent national observational study ‘‘Obesite-Epidemiologie’’ (ObEpi), the prevalence of overweight (defined by a Body Mass Index (BMI) .25 kg/m2) and obesity (BMI .30 kg/m2) among French women is 25% and 15% respectively [1]. The weight of women in childbearing age is dramatically increasing by about 0.5 to 0.7 kg/year. The Normal Weight Obese syndrome, which affects up to 37% of apparently healthy patients, is characterized by a BMI ,25 together with a high fat mass (.30%), leading to high inflammatory cytokines and a high level of oxidative stress [3,4]. Oxidative stress is well known to be detrimental in many tissues, including the female reproductive tract [5]. Compromised oocyte quality, altered pubertal development and hormonal and ovulatory dysfunction have been described

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