Sperm physiology and toxicology

Infertility is defined as the inability to conceive a child after one year of regular unprotected sexual intercourse. Causes of infertility can be of male and/or female origins, however, in about one-third of the cases, infertility remains idiopathic. In order for fertilization to occur, a sperm cell must first undergo multiple processes controlled by an increase of intracellular calcium concentration ([Ca2+]i), regulated by the sperm-specific cationic channel of Sperm (CatSper). Suboptimal activation of this channel by natural ligands such as progesterone or prostaglandins are associated with reduced male fertility and mutation in rodent or human CATSPER lead to infertility. CatSper is a highly promiscuous channel and can be modulated by various exogenous compounds such as odorants, endocannabinoids, Endocrine Disruptors as well as the effects of pharmaceutical drugs such as a class of antidepressants known as the Selective Serotonin Reuptake Inhibitors (SSRIs) (Rahban et al. (2021)).

We have developed an accurate and rapid high-throughput screening (HTS) assay to measure [Ca2+] in human sperm cells. Our goal is to investigate the iatrogenic effects of pharmaceutical drugs or selected families of compounds on intracellular calcium concentration in human sperm, focusing on potential CatSper-ligands. Compounds of interest will be selected to decipher the mechanism of action by which they act on sperm cells and evaluate their effect on sperm capacitation and hyperactivation.  We anticipate our screening to be a starting point for more thorough investigations of the drug-induced effects on human sperm fertilizing capacities.

 Recently published example: 

• Rahban R, Rehfeld A, Schiffer C, Brenker C, Egeberg Palme DL, Wang T, Lorenz J, Almstrup K, Skakkebaek NE, Strünker T, Nef S: The antidepressant Sertraline inhibits CatSper Ca2+ channels in human sperm. Hum Reprod. 2021 Sep 18;36(10):2638-2648. doi: 10.1093/humrep/deab190