Effects of spermatogenic cycle on Stem Leydig cell proliferation and differentiation

Abstract

We reported previously that stem Leydig cells (SLC) on the surfaces of rat testicular seminiferous tubules are able to differentiate into Leydig cells. The proliferation and differentiation of SLCs seem likely to be regulated by niche cells, including nearby germ and Sertoli cells. Due to the cyclical nature of spermatogenesis, we hypothesized that the changes in the germ cell composition of the seminiferous tubules as spermatogenesis proceeds may affect tubule-associated SLC functions. To test this hypothesis, we compared the ability of SLCs associated with tubules at different stages of the cycle to differentiate into Leydig cells in vitro. SLCs associated with stages IX-XI were more active in proliferation and differentiation than SLCs associated with stages VII-VIII. However, when the SLCs were isolated from each of the two groups of tubules and cultured in vitro, no differences were seen in their ability to proliferate or differentiate. These results suggested that the stage-dependent local factors, not the SLCs themselves, explain the stagedependent differences in SLC function. TGFB, produced in stage-specific fashion by Sertoli cells, is among the factors shown in previous studies to affect SLC function in vitro. When TGFB inhibitors were included in the cultures of stages IX-XI and VII-VIII tubules, stage-dependent differences in SLC development were reduced, suggesting that TGFB may be among the paracrine #

MFN2 Deficiency Impairs Mitochondrial Functions and PPAR Pathway During Spermatogenesis and Meiosis in Mice

“…In addition, the apoptotic marker (cleaved-Caspase 3) was elevated, which indicates that apoptosis was higher in the MFN2 deficient spermatocytes compared with the controls. The previous studies demonstrated the crosstalk between somatic cells and germ cells during spermatogenesis ( Wu et al, 2020 ), spermatogenic cycle has an effect on stem Leydig cell proliferation and differentiation ( Guan et al, 2019 ). Another study reported spermatogenesis involves cell–cell interactions and gene expression orchestrated by luteinizing hormone which controls the production of testosterone by Leydig cells ( Oduwole et al, 2021 ).…”

Coronavirus: A possible cause of reduced male fertility

“…Indeed, a recent study confirmed that patients with COVID‐19 suffered hypogonadotropic hypogonadism as the disease the progressed, implying that the secretory function of Leydig cells might be impaired by the novel coronavirus 17 . Testosterone is essential to preserve male fertility and to support Sertoli cell maturation and the development of Leydig cells 42 . Extensive evidence from clinical and laboratory studies implied that testosterone deficiency is accompanied by atrophy of the testicular parenchyma and degradation in the seminiferous tubules, 43,44 and in summary, testosterone is necessary for men to maintain the blood‐testis barrier, spermatogenesis, and fertility.…”

“…17 Testosterone is essential to preserve male fertility and to support Sertoli cell maturation and the development of Leydig cells. 42 Extensive evidence from clinical and laboratory studies implied that testosterone deficiency is accompanied by atrophy of the testicular parenchyma and degradation in the seminiferous tubules, 43,44 and in summary, testosterone is necessary for men to maintain the blood- or luteinizing hormone (LH), it is an ideal marker for spermatogenesis and a better indicator of sterility. 46,47 SARS-CoV-2 has a high affinity for human ACE2, which suggests that the virus might concentrate on Sertoli cells.…”

Action and Interaction between Retinoic Acid Signaling and Blood–Testis Barrier Function in the Spermatogenesis Cycle

“…The BTB is one of the tightest blood-tissue barriers because it consists of tight junctions (TJs), gap junctions (GJs), demosomes, and ectoplasmics [8]. The BTB can limit the diffusion of substances and prevent germ cells from immune cells in the circulatory and peripheral immune systems [9,10]. The disruption of BTB junctions will cause male infertility because germ cells will fail to cross from the basal to the adluminal compartment and will be stalled in an undifferentiated state [11].…”