Non-obstructive azoospermia (NOA) severely affects male infertility, however, the deep mechanisms of this disease are rarely interpreted. In this study, we find that undifferentiated spermatogonial stem cells (SSCs) still exist in the basal compartment of the seminiferous tubules and the blood–testis barrier (BTB) formed by the interaction of neighbor Sertoli cells (SCs) is incomplete in NOA patients with spermatogenic maturation arrest. The adhesions between SCs and germ cells (GCs) are also broken in NOA patients. Meanwhile, the expression level of geranylgeranyl diphosphate synthase ( Ggpps ), a key enzyme in mevalonate metabolic pathway, is lower in NOA patients than that in obstructive azoospermia (OA) patients. After Ggpps deletion specifically in SCs, the mice are infertile and the phenotype of the SC- Ggpps −/− mice is similar to the NOA patients, where the BTB and the SC–GC adhesions are severely destroyed. Although SSCs are still found in the basal compartment of the seminiferous tubules, fewer mature spermatocyte and spermatid are found in SC- Ggpps −/− mice. Further examination suggests that the defect is mediated by the aberrant protein isoprenylation of RhoA and Ras family after Ggpps deletion. The exciting finding is that when the knockout mice are injected with berberine, the abnormal cell adhesions are ameliorated and spermatogenesis is partially restored. Our data suggest that the reconstruction of disrupted BTB is an effective treatment strategy for NOA patients with spermatogenic maturation arrest and hypospermatogenesis.

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease that leads to progressive destruction of lung function. However, the mechanisms underlying the progression of LAM remain unknown. Recent studies demonstrated that miR-124-3p (hereinafter referred to as miR-124) is a downregulated miRNA in tumors and it is still unclear whether miR-124 participates in LAM. In the present study, it was revealed that miR-124 was downregulated in LAM specimens and overexpression of miR-124 resulted in the apoptosis of TSC2-deficient cells via RXRα (retinoid X receptor α), while slightly influencing TSC2 wild-type cells. Furthermore, a xenograft model demonstrated that the miR-124/RXRα axis regulated the growth and fatty acid oxidation genes in TSC2-null cells. Altogether, our results revealed the suppressive functions and mechanisms of miR-124 in LAM progression, providing novel therapeutic targets for LAM treatment.