# Clinical Electrophysiology and Mathematical Modeling for Precision Diagnosis of Infertility

## TL;DR

This review explores how measuring cell electrical activity and using mathematical models can help identify key targets for treating infertility, focusing on Sertoli cells and their response to hormones.

## Contribution

The paper introduces a precision approach combining electrophysiology and modeling to identify disease targets in male infertility.

## Key findings

- Electrophysiology and mathematical modeling can pinpoint altered ionic channels in disease.
- Sertoli cells regulate biological activity through coordinated channel activity influenced by hormones.
- These methods support drug development and repositioning for infertility treatment.

## Abstract

How can cellular electrophysiology measurements and mathematical modeling of ionic channels help to identify pivotal targets in disease-related cell signaling? The purpose of this review is to highlight the advantages and disadvantages of using both of these complementary techniques to determine molecular targets that may be structurally or functionally altered in a specific disease. In addition, both electrophysiology measurements and mathematical modeling may improve coordinated drug development, accelerate the prediction of new drugs, and facilitate repositioning of pharmacological agents. This review focuses on the data obtained from electrophysiology and mathematical model approaches, including intracellular recording, cellular patch clamp measurements, and the Hodgkin and Huxley equation, as key precision methodologies. To this end, seminiferous tubules, the Sertoli cell line (TM4), and/or primary cultures of Sertoli cells were used to explore the role of follicle-stimulating hormone (FSH), thyroid hormones, retinol, testosterone, and 1,25(OH)2 vitamin D3 in the coordinated activation or inhibition of ionic channels essential for male fertility. Based on the discussed data, Sertoli cells precisely regulate their biological activity by coordinating channel activity according to the hormonal environment and the nutritional requirements required for germ cell development.