Brain and testis: more alike than previously thought?

Brain and testis: more alike than previously thought? Bárbara Matos, Stephen J. Publicover, Luis Filipe C. Castro, Pedro J. Esteves and Margarida Fardilha. June 2 2021. https://doi.org/10.1098/rsob.200322

Abstract: Several strands of evidence indicate the presence of marked similarities between human brain and testis. Understanding these similarities and their implications has become a topic of interest among the scientific community. Indeed, an association of intelligence with some semen quality parameters has been reported and a relation between dysfunctions of the human brain and testis has also been evident. Numerous common molecular features are evident when these tissues are compared, which is reflected in the huge number of common proteins. At the functional level, human neurons and sperm share a number of characteristics, including the importance of the exocytotic process and the presence of similar receptors and signalling pathways. The common proteins are mainly involved in exocytosis, tissue development and neuron/brain-associated biological processes. With this analysis, we conclude that human brain and testis share several biochemical characteristics which, in addition to their involvement in the speciation process, could, at least in part, be responsible for the expression of a huge number of common proteins. Nonetheless, this is an underexplored topic, and the connection between these tissues needs to be clarified, which could help to understand the dysfunctions affecting brain and testis, as well as to develop improved therapeutic strategies.

1. Introduction

The human body is an orchestrated set of different organs that work together, contributing to the maintenance of overall health and homeostasis. The human brain is the control center of the nervous system, playing a critical coordination role. It receives signals from sensory organs and translates them into functional information to multiple physiological compartments such as muscles and glands. In addition, the brain is also responsible for speech production, memory storage, and the elaboration of thought and emotion [1,2]. The human testis is the male gonad, and is of the utmost importance for reproduction and species evolution. It has two main functions: production of gametes (sperm) and synthesis/secretion of hormones (primarily, testosterone) [3,4].

Despite these clearly dissimilar functions and the apparent structural and morphological differences between human brain and testis, in the last four decades it has become increasingly evident that these tissues share several features. The similarity was further confirmed by analysis of gene expression, with evidence that human brain and testis, among all the organs of the body, share the highest number of genes [5,6]. More recently, authors found a positive correlation between general intelligence and three key measures of semen quality: sperm concentration, sperm count and sperm motility [7]. A possible association between male sexual dysfunction and neurological disorders was also proposed by several authors [8,9]. These findings raise some interesting questions. (i) Why do the human brain and testis share a similar gene expression profile? (ii) Have these tissues a similar cellular organization and cooperation between cell types? (iii) Are their functions related? (iv) What are the implications of the similarities between human brain and testis?

In this context, we review the similarities between human brain and testis, and between human neuron and sperm at the cellular and molecular levels. The proteomic profile of the two human tissues (brain and testis) and the two types of cells (neuron and sperm) were also compared and critically discussed.