Progesterone utilizes the PI3K-AKT pathway in human spermatozoa to regulate motility and hyperactivation but not acrosome reaction

  title={Progesterone utilizes the PI3K-AKT pathway in human spermatozoa to regulate motility and hyperactivation but not acrosome reaction},
  author={Vrushali Sagare-Patil and Manvi Vernekar and Mosami Galvankar and Deepak N Modi},
  journal={Molecular and Cellular Endocrinology},

Identification of motility-associated progesterone-responsive differentially phosphorylated proteins.

It is proposed that progesterone activates both kinase and phosphatase pathways, leading to changes in the phosphorylation of many proteins in sperm flagella to increase motility.

Activation of the Pi3k/Akt Pathway and Modulation of Phosphodiesterase Activity via Membrane Progestin Receptor-Alpha (mPRalpha) Regulate Progestin-Initiated Sperm Hypermotility in Atlantic Croaker1

The results suggest that mPRalpha-mediated progestin stimulation of sperm motility in croaker through Pi3k/Akt is dependent on maintenance of Pde activity and a reduction in internal cAMP concentrations.

Progesterone increases capacitation and exerts a prosurvival effect in sperm via Akt activation

This study results suggest that P4 does not influence sperm motility; however, it increases sperm tyrosine phosphorylation, activates AKT (Protein kinase B), and suppresses caspase-3 (at a specific concentration of 750 ng/ul).

Progesterone requires heat shock protein 90 (HSP90) in human sperm to regulate motility and acrosome reaction

HSP90 levels are downregulated in oligoasthenozoospermia, and its functional inhibition attenuates progesterone-mediated sperm motility and acrosome reaction.

Fibronectin stimulates human sperm capacitation through the cyclic AMP/protein kinase A pathway.

Fibronectin is a novel discovery that extends the current knowledge concerning normal and pathological sperm physiology as well as events that regulate the process of fertilization.

The role and importance of cofilin in human sperm capacitation and the acrosome reaction

Gelsolin and cofilin play a similar role in F-actin depolymerization prior to the acrosome reaction but their pattern of phosphorylation/inactivation during the capacitation process is different.

Signaling mechanisms in mammalian sperm motility

This review describes and discusses the main signaling pathways involved in primary and hyperactivated motility, as well as the bioenergetic mechanisms necessary to produce energy to fuel sperm motility.

Leucine mediates autophagosome-lysosome fusion and improves sperm motility by activating the PI3K/Akt pathway

The data suggest that short-term treatment with leucine could increase zebrafish sperm motility by affecting the autophagy and inhibiting the fusion of autophagosome and lysosomes, depending on the activation of PI3K/Akt signaling pathway.

Phosphatidylinositol 3-Kinase δ-Specific Inhibitor-Induced Changes in the Ovary and Testis in the Sprague Dawley Rat and Cynomolgus Monkey

The results suggest species-related differences in PI3K isoform-specific control on reproductive organs may be important in spermatogenesis maturation in the cynomolgus monkey.



Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa.

It is demonstrated that short-term incubation of spermatozoa with progesterone induces phosphorylation and activation of ERKs, resulting in redistribution of the proteins from the post-acrosomal region to the equatorial segment within the sperm head.

Differential concentration and time dependent effects of progesterone on kinase activity, hyperactivation and acrosome reaction in human spermatozoa.

The results imply that although the spermatozoa are sensitive to low concentrations of progesterone, they only activate motility and tyrosine kinase activation; higher concentrations are required to induce hyperactivation and acrosome reaction probably by activating multiple kinase pathways including the MAPK and AKT.

Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A

It is demonstrated that PI 3-kinase negatively regulates sperm motility by interfering withAKAP3-PKA binding, providing the first evidence of a molecular mechanism by which PKA can be targeted to sperm tails by interaction with tyrosine phosphorylated form of AKAP3.

Protein kinase C activation during progesterone-stimulated acrosomal exocytosis in human spermatozoa.

These results provide the first direct evidence that PKC activation plays a role in the signal transduction pathway underlying acrosomal exocytosis in progesterone-stimulated capacitated spermatozoa.

Progesterone activates Janus Kinase 1/2 and activators of transcription 1 (JAK1‐2/STAT1) pathway in human spermatozoa

It is concluded that in human spermatozoa, the JAK1/2 pathway is activated upon capacitation and is further modulated by progesterone; the biological processes controlled by this pathway in sperm need to be elucidated.

Inhibitors of phosphoinositide 3-kinase, LY294002 and wortmannin, affect sperm capacitation and associated phosphorylation of proteins differently: Ca2+-dependent divergences.

The data show that sperm incubated with LY294002 undergo capacitation and increased Tyr phosphorylation of specific sperm proteins in a manner similar to that promoted by the capacitation inducer fetal cord serum ultrafiltrate (FCSu), as well as double phosphorylated of the threonine (Thr)-glutamine (Glu)-Tyr motif.

Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation.

Results suggest that PI 3-kinase is involved in the human sperm acrosome reaction.

Inhibition of phosphatidylinositol 3-kinase modifies boar sperm motion parameters.

The data suggest that PI3-K plays a negative role, regulating boar sperm motion parameters through a possible inhibition of the cAMP/PKA activating pathway, and since some Computer Aided Sperm Analysis (CASA)-derived parameters have been related to field fertility, these results point to the possibility of modulating sperm motile quality by modifying the PI2-K cellular pathway.

Role of PI3-Kinase and PI4-Kinase in Actin Polymerization During Bovine Sperm Capacitation1

The results suggest that spermine, which is present in the ejaculate, regulates PI4K activity during the capacitation process in vivo, and two alternative pathways lead to PI4k activation.