Effect of estradiol on in vitro maturation of immature oocytes in cyclophosphamide-induced premature ovarian failure in NMRI mice: An experimental study.

Abstract

Background: Premature ovarian failure (POF) is a condition characterized by the loss of ovarian function, leading to infertility.

Objective: This study aims to examine how estradiol supplementation impacts the in vitro maturation of immature oocytes in NMRI female mice exhibiting cyclophosphamide-induced POF.

Materials and methods: In this experimental study, 15 female NMRI mice (8-10 wk, 30 $\pm$ 5 gr) were divided into 3 groups: control, sham, and treatment. The treatment group was divided into 3 categories. Treatment group 1, which added 0.5 μg/ml estradiol to the basic culture medium, and treatment groups 2 and 3, which were added to the culture medium, respectively. They added 1 and 1.5 µg/ml of estradiol to their basic culture medium. The treatment group received cyclophosphamide injections for 21 days to induce POF and then was treated with different doses of estradiol. The sham group also received all necessary interventions except estradiol treatment. After the induction, histological studies were conducted on the ovaries of all groups. Additionally, after stimulating and separating the ovules from the ovary, they were cultured in in vitro.

Results: Analysis of oocyte maturity stages showed distinct features. Germinal vesicle oocytes' lowest percentage was in control (3.13%), and highest in sham (76.25%) (p $<$ 0.0001). Estradiol dose inversely affected immature oocyte maturation, with the lowest in treatment group 3. Germinal vesicle breakdown oocyte percentage increased with estradiol dose. Metaphase II oocytes' highest maturation was in control (64.00%), and lowest in sham (5.00%) (p $<$ 0.0001). Treatment groups showed varying rates. Degenerate oocyte percentages were lowest in control (1.80%), and highest in sham (10.27%) (p $<$ 0.0001).

Conclusion: Our study showed that using a dose of 1.5 μg/ml estradiol in vitro results in the highest oocyte maturation in the POF condition and contributes to the existing knowledge on POF and provides insights into potential therapeutic interventions aimed at improving fertility outcomes in individuals with POF.