The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.

Chinese abstract

多囊卵巢综合征（PCOS）是育龄妇女常见的内分泌疾病, 其特征为卵巢多囊样改变, 稀发排卵/无排卵和高雄激素血症。不是仅仅只有无排卵可以降低PCOS患者的生育能力, 子宫内膜功能障碍也可降低PCOS患者的生育能力。Wnt是负责子宫内膜增殖的信号传导通路, 其受雌二醇的强烈调节。为了确定枸橼酸克罗米芬（CC）和来曲唑的作用, 在月经第12天起接受100毫克CC或5毫克来曲唑的PCOS女性以及未经治疗女性的子宫内膜样本, 测量Wnt / b-连环蛋白信号传导的一些主要配体的表达, 包括Wnt7a, Wnt3和Wnt8b。值得注意的是, 来曲唑组的平均雌激素浓度低于CC组, 平均孕酮浓度高于CC组。来曲唑组的平均子宫内膜厚度（ET）显著高于CC组。CC组的Wnt7a, Wnt3和Wnt8b的蛋白表达和mRNA的评估显著低于来曲唑组和对照组。与CC相比, 来曲唑可以在PCOS患者子宫内膜的增殖期提供更好的分子反应, 类似于自然周期。CC降低了Wnt3, Wnt7a和Wnt8b的配体表达, 导致子宫内膜功能障碍。

Keywords:

• Polycystic ovary syndrome
• clomiphene citrate
• letrozole
• tndometrium
• Wnt ligands

Acknowledgements

The authors thank the staff of Cellular and Molecular Research Center, Iran University of Medical Sciences who were involved in this study.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This project was supported by research grant from Tehran University of Medical Sciences and Health Services [grant no. 26168].