New advances on the study of masculine fertility

The study, which was published in Biological Chemistry, provides key information to develop new diagnosis and therapeutic tools for infertile patients and work on new non-hormonal contraceptive methods.

Buffone Group - Photo: Courtesy researcher

During sperm capacitation, in which the sperm is prepared to fertilize the oocyte, the sperm nucleus is “asleep.” This means that it is transcriptionally inactive and the necessary transformation occurs through its interaction with the stimuli of the environment in which it is.

The objective of the study published in Biological Chemistry was to find and explain how signaling pathways give those stimuli.

The ions (charged molecules) of the male and female reproductive tract play a vital role to activate the molecular steps that make the sperm acquire fertilization capacity. When the sperms enter the female reproductive tract, they find ion concentrations different from the ones at the epididymis, so this triggers a cascade of molecular events that leads to sperm capacitation.

Despite the information provided by previous studies in which one of those ions, the bicarbonate (HCO3) plays a key role when it directly activates those molecular signaling pathways, scientists did not know how those ones entered the cell.

The study conducted by the Cell and Molecular Biology of Reproduction laboratory led by Mariano Buffone at the Institute of Biology and Experimental Medicine (IBYME), proved that the bicarbonate initially enters the cell through the ion cotransport channel called NBC, described by the group.  This means that through one channel two ions enter together and in the case of the bicarbonate, it enters together with the sodium.

When the bicarbonate gets into the cell, it activates one enzyme, the adenilatociclasa soluble. This enzyme produces a very important messenger, the cyclic AMP, essential molecular steps to make the sperm translate the signal provided by the bicarbonate to regulate the ion channels and control the membrane potential.

During sperm capacitation, it is a known fact that a change of potential of the cell membrane takes place. This means that there is an unbalance between the charge inside the cell and the charge of the external part. This change has always been attributed to the outing of positive ions (potassium) through a group of channels called SLO. However, the group discovered that there was also another factor that contributes to this phenomenon: the entrance channel of negative sodium ions (ENaC) closes, preventing the entrance of negative charge.

“The main contribution of this study is that it managed to clarify how the first steps are connected to activate these pathways with more terminal facts, such as the changes in the membrane potential”, Dr Buffone concluded and added: “To understand the molecular steps that govern those processes is fundamental to develop new therapeutic and diagnosis tools for infertile patients and new non-hormonal contraceptive methods.”

About the study:

J Biol Chem. 2018 May 9. pii: jbc.RA118.003166. doi: 10.1074/jbc.RA118.003166 [Epub ahead of print]
CFTR/ENaC dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC
Puga Molina LC, Pinto NA, Torres NI, Gonzalez-Cota AL, Luque GM, Balestrini PA, Romarowski A, Krapf D, Santi CM, Trevino CL, Darszon A, Buffone MG.

Credits: Institutional Communication– IBYME