Letrozole Reduces Ovulatory Responsiveness in In Vitro-Grown Mouse Follicles.

IF 3.3 3区医学 Q2 OBSTETRICS & GYNECOLOGY

Reproductive Medicine and Biology Pub Date : 2026-04-15 eCollection Date: 2026-01-01 DOI:10.1002/rmb2.70047

Tatsuya Kobayashi, Hiroshi Ishikawa, Hirokazu Tanaka, Kumiko Ishii, Akira Mitsuhashi, Hirokazu Usui, Makio Shozu, Kaori Koga

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引用次数: 0

Abstract

Purpose: This study aimed to determine whether continuous aromatase inhibition with letrozole reduces peri-ovulatory responsiveness to ovulatory stimulation in in vitro-grown mouse follicles.

Methods: Early antral follicles were isolated from 21 to 24-day-old C57BL/6jjcl mice and cultured individually for 5 days with letrozole (0.01, 0.1, or 1 μM) or vehicle. Follicle survival and growth were assessed by measuring follicle diameter. Ovulatory responsiveness was evaluated by hCG/EGF stimulation. Expression of ovulation-related genes (Lhcgr, Ptgs2, and Runx1) and a luteinization-related gene (Foxo1) was analyzed using RT-qPCR. The effect of estradiol supplementation was also examined.

Results: Letrozole did not affect follicle survival or growth. However, ovulation rates were reduced in a dose-dependent manner (p < 0.0001). At 0.1 μM, letrozole significantly decreased mRNA levels of Lhcgr, Runx1, and Ptgs2 compared with vehicle-treated follicles. Estradiol supplementation restored the expression of these genes and partially rescued ovulatory capacity. In contrast, Foxo1 expression increased in letrozole-treated follicles and was attenuated by estradiol.

Conclusions: Continuous letrozole exposure reduces ovulatory responsiveness in in vitro-grown mouse follicles and is associated with decreased Lhcgr expression after hCG stimulation, likely due to estrogen deficiency. These findings suggest that prolonged aromatase inhibition during follicular growth may impair acquisition of peri-ovulatory competence.

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来曲唑降低体外培养小鼠卵泡的排卵反应性。

目的：本研究旨在确定来曲唑持续抑制芳香酶是否会降低体外培养小鼠卵泡对排卵刺激的排卵期反应性。方法：取21 ~ 24日龄C57BL/6jjcl小鼠早期窦卵泡，分别用来曲唑（0.01、0.1、1 μM）或载药培养5 d。通过测量卵泡直径来评估卵泡的存活和生长。通过刺激hCG/EGF来评估排卵反应。使用RT-qPCR分析排卵相关基因（Lhcgr、Ptgs2和Runx1）和黄体化相关基因（Foxo1）的表达。我们还研究了补充雌二醇的效果。结果：来曲唑对卵泡存活和生长无影响。然而，与载体处理的卵泡相比，排卵率呈剂量依赖性降低（p Lhcgr、Runx1和Ptgs2）。补充雌二醇恢复了这些基因的表达，部分恢复了排卵能力。相比之下，Foxo1在来曲唑处理的卵泡中表达增加，雌二醇则减弱。结论：持续使用来曲唑可降低体外培养小鼠卵泡的排卵反应性，并与hCG刺激后Lhcgr表达降低有关，可能是由于雌激素缺乏。这些发现表明，在卵泡生长过程中，长时间的芳香酶抑制可能会损害卵泡围排卵期能力的获得。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive Medicine and Biology Multiple-

CiteScore

5.70

自引率

5.90%

发文量

审稿时长

20 weeks

期刊介绍： Reproductive Medicine and Biology (RMB) is the official English journal of the Japan Society for Reproductive Medicine, the Japan Society of Fertilization and Implantation, the Japan Society of Andrology, and publishes original research articles that report new findings or concepts in all aspects of reproductive phenomena in all kinds of mammals. Papers in any of the following fields will be considered: andrology, endocrinology, oncology, immunology, genetics, function of gonads and genital tracts, erectile dysfunction, gametogenesis, function of accessory sex organs, fertilization, embryogenesis, embryo manipulation, pregnancy, implantation, ontogenesis, infectious disease, contraception, etc.