Effects of progesterone on sperm function: mechanisms of action

Abstract

Progesterone stimulates sperm functions, e.g. hyperactivation, acrosome reaction, binding to oocyte zona pellucida and penetration rate into the hamster oocyte. The physiological relevance of these effects has been shown using female genital tract fluids which modulate sperm function according to their progesterone content. Progesterone interacts with specific sperm binding sites that, unlike the classic nuclear receptors, are located on the plasma membrane of the spermatozoon. Binding studies have revealed the presence of two classes of progesterone receptors in the human spermatozoon, one class has an elevated affinity constant (nanomolar) and is specific for progesterone, whereas the other class has an affinity constant in the micromolar range and binds equally well other hydroxylated progesterone derivatives. Following exposure to progesterone, the main event is a rapid (within seconds) increase of the intracellular free calcium concentration, followed by a sustained rise lasting for several minutes (plateau phase). Both these calcium transients are dependent upon entry of extracellular calcium. The nature of the calcium channel that mediates the effects of progesterone is, currently, unknown. It has been postulated that it may be: (i) part of the progesterone receptor; (ii) voltage-dependent; or (iii) operated by second messengers following activation of the progesterone receptor. Progesterone also modulates sperm function by stimulating a trypsin-like proteolytic activity, the biosynthesis of polyamine (putrescine and spermidine), phospholipase A2 activity and protein tyrosine kinase activity in the sperm cell. Recent studies have shown that chloride ion efflux is vital for progesterone to promote the acrosome reaction. This effect is achieved by interaction with a sperm membrane receptor which resembles the neuronal GABA(A) receptor. Accordingly, GABA(A) receptors have been found in the spermatozoon plasma membrane and GABA stimulates hyperactivation and promotes the acrosome reaction.

Tissue expression of the nuclear progesterone receptor in male non-human primates and men

“…It should be considered that, together with the adrenal gland, the testis is exposed to the highest progesterone concentrations of the body and that the scant PR expression observed could be just a marker of estrogenic activity. As a non-genomic effect, progesterone stimulates sperm hyperactivation and acrosome reaction (Calogero et al 2000), an effect certainly unwanted in the epididymis. PR expression in the epididymis might alter the flow (Ergün et al 1997) and could also prevent sperm from premature acrosome reaction.…”

Identification of a 71 kDa protein as a putative non-genomic membrane progesterone receptor in boar spermatozoa

“…Lately, non-genomic mPRs have been reported in conjunction with non-genomic functions of progesterone (Zhu et al 2003). In mammalian reproduction, progesterone has been implicated to be involved in AR (reviewed by Calogero et al 2000), in human (Osman et al 1989, Baldi et al 1995, Patrat et al 2000, mouse (Melendrez et al 1994), stallion (Meyers et al 1995), golden hamster (Meizel et al 1990), dog (Sirivaidyapong et al 1999), goat (Somanath et al 2000 and boar (Jang & Yi 2002). Progesterone, by binding to a non-genomic mPR, has been reported to induce AR via intracellular signal transduction cascades (Kopf 2002).…”

An in vitro study of the effect of mifepristone and ulipristal acetate on human sperm functions

“…It induces Ca 2+ influx into spermatozoa through the CatSper channel and triggers multiple Ca 2+ -dependent physiological responses essential for successful fertilization, such as acrosome reaction and hyperactivation (Calogero et al, 2000;Kirkman-Brown et al, 2002;Strunker et al, 2011). It has been proposed that progesterone is an enhancer of ZP-induced acrosome reaction (Roldan et al, 1994).…”