Folliculogenesis Is Not Fully Inhibited during GnRH Analogues Treatment in Mice Challenging Their Efficiency to Preserve the Ovarian Reserve during Chemotherapy in This Model
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
References
The GnRH antagonist reduces chemotherapy-induced ovarian damage in rats by suppressing the apoptosis
Long-term adverse effects of cyclophosphamide on follicular growth and angiogenesis in mouse ovaries
Citations
Methods Mentioned
Software Mentioned
Related Concepts
Related Feeds
Apoptosis in Cancer
Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.
AKT Pathway
This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis