Abstract
Sphingosine phosphate lyase 1 (SGPL1) is a highly conserved enzyme that irreversibly degrades sphingosine-1-phosphate (S1P). Sgpl1-knockout mice fail to develop germ cells, resulting in infertility. However, the molecular mechanism remains unclear. The results of the present study showed that SGPL1 was expressed mainly in granulosa cells, Leydig cells, spermatocytes, and round spermatids. Sgpl1 deletion led to S1P accumulation in the gonads. In the ovary, S1P decreased natriuretic peptide receptor 2 (NPR2) activity in granulosa cells and inhibited early follicle growth. In the testis, S1P increased the levels of cyclin-dependent kinase inhibitor 1A (p21) and apoptosis in Leydig cells, thus resulting in spermatogenesis arrest. These results indicate that Sgpl1 deletion increases intracellular S1P levels, resulting in the arrest of female and male germ cell development via different signaling pathways.
Highlights
Normal gonad development is crucial for the production of mature gametes and the secretion of sexual hormones[1]
Follicular development initiates with the transition of the primordial stage to preantral follicles, and these preantral follicles develop into large antral follicles under follicle-stimulating hormone (FSH) stimulation[2]
Sphingosine phosphate lyase 1 (SGPL1) was strongly localized in the cytoplasm of granulosa cells and theca cells but was slightly expressed in oocytes (Fig. 1a)
Summary
Normal gonad development is crucial for the production of mature gametes and the secretion of sexual hormones[1]. The follicle is the basic unit of the ovary. Follicular development initiates with the transition of the primordial stage to preantral follicles, and these preantral follicles develop into large antral follicles under follicle-stimulating hormone (FSH) stimulation[2]. Natriuretic peptide type C (NPPC, known as CNP) and its receptor natriuretic peptide receptor 2 (NPR2) maintain meiotic arrest of oocytes within full-grown follicles[3,4]. When luteinizing hormone (LH) surges occur, NPR2 guanylyl cyclase activity is decreased, and oocytes resume meiosis[5,6].
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