Release of Porcine Sperm from Oviduct Cells is Stimulated by Progesterone and Requires CatSper

Abstract

Sperm storage in the female reproductive tract after mating and before ovulation is a reproductive strategy used by many species. When insemination and ovulation are poorly synchronized, the formation and maintenance of a functional sperm reservoir improves the possibility of fertilization. In mammals, the oviduct regulates sperm functions, such as Ca2+ influx and processes associated with sperm maturation, collectively known as capacitation. A fraction of the stored sperm is released by unknown mechanisms and moves to the site of fertilization. There is an empirical association between the hormonal milieu in the oviduct and sperm detachment; therefore, we tested directly the ability of progesterone to induce sperm release from oviduct cell aggregates. Sperm were allowed to bind to oviduct cells or an immobilized oviduct glycan and then challenged with progesterone, which stimulated the release of 48% of sperm from oviduct cells or 68% of sperm from an immobilized oviduct glycan. The effect of progesterone on sperm release was specific; pregnenolone and 17α-OH-progesterone did not affect sperm release. Ca2+ influx into sperm is associated with capacitation and development of hyperactivated motility. Progesterone increased sperm intracellular Ca2+, which was abrogated by blocking the sperm–specific Ca2+ channel CatSper with NNC 055-0396. NNC 055-0396 also blocked the progesterone-induced sperm release from oviduct cells or immobilized glycan. An inhibitor of the non-genomic progesterone receptor that activates CatSper similarly blocked sperm release. This is the first report indicating that release of sperm from the sperm reservoir is induced by progesterone action through CatSper channels.

Two-Player Game in a Complex Landscape: 26S Proteasome, PKA, and Intracellular Calcium Concentration Modulate Mammalian Sperm Capacitation by Creating an Integrated Dialogue—A Computational Analysis

“…Sperm from CatSper-null mice are motile, but sterile because they fail to hyperactivate and cannot fully ascend the female genital tract or penetrate the zona pellucida [ 24 ]. Moreover, they were recently shown to be necessary for the sperm detachment from the oviductal reservoir in swine [ 25 ]. Sperm intracellular Ca 2+ can be released from the acrosome and RNE by inositol triphosphate and ryanodine receptors—IP3R and RyR, respectively [ 4 , 23 ].…”

Natural Mating Differentially Triggers Expression of Glucocorticoid Receptor (NR3C1)-Related Genes in the Preovulatory Porcine Female Reproductive Tract

“…This receptor, is responsible for removing inhibitors of the cation channel of sperm (CatSper), in an antagonist competition mechanism, consequently inhibiting hyperactivation [84]. Thus, GCs could be exerting an anti-capacitation effect by preventing premature CatSper activation occurring prior to ovulation, as well as preventing GCs from competing with progesterone, which is necessary for sperm hyperactivation, release from the reservoir oviductal epithelial cells [85], and chemotaxis [86]. Activation of CatSper channels by progesterone, or even prostaglandins, seems to differ among species [87].…”

Does the Pre-Ovulatory Pig Oviduct Rule Sperm Capacitation In Vivo Mediating Transcriptomics of Catsper Channels?

“…Moreover, inhibition of ABHD2 has been shown to suppress porcine sperm release from oviduct reservoir [63], which might associate the downregulation of ABHD2 found in this study with the fact that sperm release from oviductal cells was not fully achieved, considering the timing of tissue sampling (24h post-insemination, absence of spontaneous ovulation, and lack of pre-ovulatory progesterone surge (P4 = 0.77 ± 0.35 pg/mL in peripheral blood) [30,48]. An increase in progesterone concentrations immediately prior to and following ovulation facilitates the release of spermatozoa from the oviduct epithelium so that they can reach the site of fertilization [63], a process that occurs sequentially [48], rather than all at once (as it is usually achieved in vitro [19]). The reason why many of the transcripts described in the present work are highly overrepresented in the mating group in comparison with the P1-AI group, despite both containing spermatozoa, may be explained by the fact that they represent two different procedures, natural mating and artificial insemination (AI).…”