Proteomic changes in uterine flushings after levonorgestrel treatment and effects on sperm function

Area of Science:

• Reproductive biology
• Endocrinology
• Proteomics

Background:

• Levonorgestrel (LNG) is used for emergency contraception.
• LNG's mechanism includes ovulation inhibition and potential effects on sperm functionality.
• Endometrial secretions may influence sperm function.

Purpose of the Study:

• To characterize molecules in female reproductive tract secretions affecting human spermatozoa.
• To analyze protein content changes in uterine flushings after LNG treatment.
• To investigate the impact of LNG on sperm functionality.

Main Methods:

• Collected uterine flushings during the periovulatory phase from control and LNG-treated cycles.
• Utilized lectin affinity analysis and 2D gel electrophoresis to analyze protein profiles.
• Employed mass spectrometry and Western blot to identify and validate differentially expressed proteins, including lactotransferrin (LTF).

Main Results:

• Identified 31 differentially expressed proteins in uterine secretions (8 upregulated, 23 downregulated) following LNG treatment.
• Lactotransferrin (LTF) was significantly upregulated by LNG.
• LTF demonstrated dose-related inhibition of calcium ionophore-induced acrosome reaction and protein tyrosine phosphorylation in sperm.

Conclusions:

• LNG alters the uterine proteome, potentially compromising human sperm capacitation.
• These proteomic changes suggest additional mechanisms for LNG's emergency contraceptive action.
• The study highlights the role of endometrial secretions in mediating LNG's effects on sperm functionality.