Folliculogenesis Is Not Fully Inhibited during GnRH Analogues Treatment in Mice Challenging Their Efficiency to Preserve the Ovarian Reserve during Chemotherapy in This Model

PloS One
Florence HoricksIsabelle Demeestere

Abstract

As many chemotherapy regimens induce follicular depletion, fertility preservation became a major concern in young cancer patients. By maintaining follicles at the resting stage, gonadotropin-releasing hormone analogues (GnRHa) were proposed as an ovarian-protective option during chemotherapy. However, their efficacy and mechanisms of action remain to be elucidated. Mice were dosed with cyclophosphamide (Cy, 100-500 mg/kg i.p) to quantify follicular depletion and evaluate apoptosis at different times. We observed a dose-dependent depletion of the follicular reserve within 24 hours after Cy injection with a mean follicular loss of 45% at the dose of 200mg/kg. Apoptosis occurs in the granulosa cells of growing follicles within 12 hours after Cy treatment, while no apoptosis was detected in resting follicles suggesting that chemotherapy acutely affects both resting and growing follicles through different mechanisms. We further tested the ability of both GnRH agonist and antagonist to inhibit oestrus cycles, follicular growth and FSH secretion in mice and to protect ovarian reserve against chemotherapy. Although GnRHa were efficient to disrupt oestrus cycles, they failed to inhibit follicular development, irrespective of the doses a...Continue Reading

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Citations

Oct 1, 2016·Cell Death and Differentiation·Valerio RossiFrancesca G Klinger
Dec 6, 2019·International Journal of Molecular Sciences·Paola ScaruffiLucia Del Mastro
Sep 25, 2019·International Journal of Molecular Sciences·Xia HaoKenny A Rodriguez-Wallberg
Oct 11, 2019·International Journal of Molecular Sciences·Chrysanthi AlexandriIsabelle Demeestere

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