Abstract

PIWI-interacting RNAs (piRNAs) play an important role in gametogenesis, fertility and embryonic development. The current study investigated the effect of different doses of pregnant mare serum gonadotrophin/human chorionic gonadotrophin (PMSG/hCG) and repeated ovarian stimulation (OS) on the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9, qnd Mitopld genes, which have crucial roles in the biogenesis and function of piRNAs. Here, we found that after treatment with 7.5 I.U. PMSG/hCG and two repeated rounds of OS, both the mRNA and protein levels of Tdrd9, Tdrd1 and Mael showed the greatest decrease in the ovarian tissue, but the plasma E2 levels showed the strongest increases (p<0.05). However, we found that the Mitopld, Miwi and Mili gene levels were decreased significantly after treatment with 12.5 I.U. PMSG/hCG. Our results suggested that exogenous gonadotropin administration leads to a significant decrease in the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9 and Mitopld genes, which are critically important in the piRNA pathway, and the changes in the expression levels of Tdrd9, Tdrd1 and Mael may be associated with plasma E2 levels. New comprehensive studies are needed to reduce the potential effects of OS on the piRNA pathway, which silences transposable elements and maintains genome integrity, and to contribute to the safety of OS.

Highlights

  • Ovarian stimulation (OS) with exogenous gonadotropin injections has been used for many years as a method for increasing oocytes in animal and humans

  • In the present study, we examined whether different doses of pregnant mare serum gonadotrophin (PMSG)/ human chorionic gonadotrophin and repeated OS affect the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9, and Mitopld genes in mouse M2 oocytes and ovarian tissue

  • In our study, when the effects of OS on the expression levels of the genes involved in the PIWI-interacting RNAs (piRNAs) pathway were evaluated by quantitative real-time polymerase chain reaction (qPCR) in ovarian tissues depending on both the dose of exogenous gonadotropin administration and the number of OS cycles performed, we found that the Tdrd1, Tdrd9, and Mael expression levels decreased in all groups

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Summary

Introduction

Ovarian stimulation (OS) with exogenous gonadotropin injections has been used for many years as a method for increasing oocytes in animal and humans. Considerable progress in in vitro fertilization (IVF) has been achieved in recent years, the pregnancy rate per embryo transferred is still low [1]. Many studies comparing natural and stimulated ovarian cycles have indicated some detrimental effects of gonadotropin stimulation, and there may be a relationship between treatment with gonadotropins and a low pregnancy rate. Increased chromosomal abnormalities were found in gonadotropin-treated mice and rats, suggesting that genetic factors may be implicated in embryonic mortality [2,3,4].

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