Abstract
In vitro activation of primordial follicles is becoming more essential in assisted reproductive technologies. Vasoactive intestinal peptide (VIP) is one of the members of the neurotrophin family which has demonstrated to have an impact on follicle development in recent years. This study aims to investigate the effect of VIP on the activation of primordial follicles in neonatal rat in an in vitro culture system and to determine the relevant molecular mechanism of their activation. Ovaries of 4-day-old rats were examined for the expression of VIP receptors and were cultured in mediums containing VIP with or without inhibitors of the ERK–mTOR signalling pathway. They were then collected for histological analysis or measurement of the molecular expression of this pathway. The receptors of VIP were found in granular cells and oocytes of primordial and early-growing follicles in neonatal ovary. The ratio of growing follicle increased in the presence VIP at different concentrations, with the highest level of increase being observed in the 10−7 mol/L VIP-treated group. The ratio of PCNA-positive granular cells was also increased, while that of the apoptotic oocytes were decreased, and protein analysis showed increased phosphorylation of ERK1/2, mTOR and RPS6 in the VIP-treated group. However, the effect of VIP on the activation of primordial follicle became insignificant with the addition of MEK inhibitor (U0126) or mTORC1 inhibitor (rapamycin). This study indicated that VIP could activate neonatal rat primordial follicle through the ERK-mTOR signalling pathway, suggesting a strategy for in vitro primordial follicle recruitment.
Highlights
Cryopreservation of ovarian tissue is an important way to preserve fertility in women who are facing fertilitythreatening diseases or treatments (Ladanyi et al 2017, Kim et al 2018)
Vasoactive intestinal peptide (VIP) takes effect mainly via its receptors 1 and 2 (VPAC1 and VPAC2), so we first examined whether these two receptors exist in the neonatal rat ovary by using antiVPAC1 or VPAC2 antibody
The effect of VIP on the activation of primordial follicle in neonatal rat ovary To explore the effects of VIP on follicle development and to determine the suitable concentration for an in vitro ovarian culture system, we cultured the 4-day-old ovaries for 3 days with different concentrations of VIP (10−6 mol/L, 10−7 mol/L and 10−8 mol/L)
Summary
Cryopreservation of ovarian tissue is an important way to preserve fertility in women who are facing fertilitythreatening diseases or treatments (Ladanyi et al 2017, Kim et al 2018). Poor surgical procedure or limited ovarian tissue might cause infertility after re-transplantation (Kim et al 2018). To solve this problem, researchers are progressively exploring suitable ways to obtain matured oocytes through in vitro activation (IVA) of primordial follicle. Some researchers have obtained ovary tissue from patients with ovarian insufficiency for IVA that involves Hippo signalling disruption and protein kinase B (AKT) stimulation, followed by auto-transplantation and assisted reproductive technologies. Even though live birth was achieved after re-transplantation of the cultured ovarian tissue, the low success rate made it necessary for new IVA strategy to be developed (Suzuki et al 2015, Zhai et al 2016). Revealing the functions and mechanism of these factors may be of great benefit to primordial follicle development
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