Abstract
Mammalian spermatozoa undergo selective movement along the isthmus of the oviduct to the ampulla during ovulation, which is a prerequisite for fertilization. The factor(s) that involves in selective spermatozoa movement is still unknown. In this study, we found that the oviductal epithelium in mouse ampulla expressed high levels of natriuretic peptide type C (NPPC) in the presence of ovulated oocyte-cumulus complexes (OCCs). Spermatozoa expressed NPPC receptor natriuretic peptide receptor 2 (NPR2, a guanylyl cyclase) on the midpiece of flagellum. NPPC increased intracellular levels of cGMP and Ca2+ of spermatozoa, and induced sperm accumulation in the capillary by attraction. Importantly, spermatozoa from Npr2 mutant mice were not attracted by NPPC, preventing fertilization in vivo. Oocyte-derived paracrine factors promoted the expression of Nppc mRNA in the ampulla. Therefore, NPPC secreted by oviductal ampulla attracts spermatozoa towards oocytes, which is essential for fertilization.
Highlights
Oocytes attract spermatozoa by secreting chemical factors to promote fertilization
Nppc mRNA expression in mouse ampulla depends on stimulation of ovulated oocyte-cumulus complexes (OCCs)
We showed that ovulation stimulated natriuretic peptide type C (NPPC), which bound to natriuretic peptide receptor 2 (NPR2) on spermatozoa, to increase attraction for oocytes that reside in the ampulla, and ensure normal fertilization
Summary
Oocytes attract spermatozoa by secreting chemical factors to promote fertilization. Experimental data suggest chemical attraction for spermatozoa near the oocyte in the ampulla, to trigger fertilization[15]. Amino acid sequence analysis suggests that mouse natriuretic peptides (NPs), including type A (NPPA, known as ANP), type B (NPPB, known as BNP) and type C (NPPC, known as CNP), exhibit features similar to the chemoattractant peptides in marine invertebrates (see Supplementary Fig. S1). NPPA attracts mammalian spermatozoa in vitro[25,26], and NPPC increases human sperm motility[27]. The aim of this study was to investigate the expression pattern of NPPC in mouse oviduct and its cognate receptor natriuretic peptide receptor 2 (NPR2) on spermatozoa, and their role in sperm attraction and fertilization
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