IGSF11 is required for pericentric heterochromatin dissociation during meiotic diplotene

Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.

The Action of Oil-Related Environmental Pollutants on Male Reproductive System

The low-weight aromatic hydrocarbons benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX), are among the most common hazardous sources of environmental contamination. The present review is the first summarization the data obtained during epidemiological, animals and cell culture studies concerning BTEX action on different aspects of male reproductiontesticular cell apoptosis, spermatogenesis, cytogenetics, pituitary and peripheral hormones and intracellular signaling systems. Analysis of the available literature demonstrates that BTEX can exert hazardous effects on various reproductive sites, including the pituitary-gonadal axis, hormone receptors and intracellular signaling molecules, testicular cell apoptosis, spermatogenesis and fertility. There are indications, that BTEX reproductive effects could be due to the ability of BTEX to affect embryonal gonads, to induce testicular cell mutagenesis and destroy chromosomes, to promote accumulation of free radicals, to affect hormones and hormonal receptors, cell cycle and CNS structures regulating reproduction, but only the role of free radicals in mediating BTEX action on male reproduction has been proven by experiments yet. Some approaches to prevent negative action of BTEX are outlined.

Responses and coping methods of different testicular cell types to heat stress: overview and perspectives

To facilitate temperature adjustments, the testicles are located outside the body cavity. In most mammals, the temperature of the testes is lower than the body temperature to ensure the normal progression of spermatogenesis. Rising temperatures affect spermatogenesis and eventually lead to a decline in male fertility or even infertility. However, the testes are composed of different cell types, including spermatogonial stem cells, spermatocytes, spermatozoa, Leydig cells, and Sertoli cells, which have different cellular responses to heat stress. Recent studies have shown that using different drugs can relieve heat-stress-induced reproductive damage by regulating different signaling pathways. Here, we review the mechanisms by which heat stress damages different cells in testes and possible treatments.

The Role of Androgen Signaling in Male Sexual Development at Puberty

Puberty is characterized by major changes in the anatomy and function of reproductive organs. Androgen activity is low before puberty, but during pubertal development, the testes resume the production of androgens. Major physiological changes occur in the testicular cell compartments in response to the increase in intratesticular testosterone concentrations and androgen receptor expression. Androgen activity also impacts on the internal and external genitalia. In target cells, androgens signal through a classical and a nonclassical pathway. This review addresses the most recent advances in the knowledge of the role of androgen signaling in postnatal male sexual development, with a special emphasis on human puberty.

ITGA6+ Human Testicular Cell Populations Acquire a Mesenchymal Rather than Germ Cell Transcriptional Signature during Long-Term Culture

Autologous spermatogonial stem cell transplantation is an experimental technique aimed at restoring fertility in infertile men. Although effective in animal models, in vitro propagation of human spermatogonia prior to transplantation has proven to be difficult. A major limiting factor is endogenous somatic testicular cell overgrowth during long-term culture. This makes the culture both inefficient and necessitates highly specific cell sorting strategies in order to enrich cultured germ cell fractions prior to transplantation. Here, we employed RNA-Seq to determine cell type composition in sorted integrin alpha-6 (ITGA6+) primary human testicular cells (n = 4 donors) cultured for up to two months, using differential gene expression and cell deconvolution analyses. Our data and analyses reveal that long-term cultured ITGA6+ testicular cells are composed mainly of cells expressing markers of peritubular myoid cells, (progenitor) Leydig cells, fibroblasts and mesenchymal stromal cells and only a limited percentage of spermatogonial cells as compared to their uncultured counterparts. These findings provide valuable insights into the cell type composition of cultured human ITGA6+ testicular cells during in vitro propagation and may serve as a basis for optimizing future cell sorting strategies as well as optimizing the current human testicular cell culture system for clinical use.