title: Membrane progestin receptor alpha mediates progestin-induced sperm hypermotility and increased fertilization success in southern flounder (Paralichthys lethostigma).
abstract: Progestin hormones stimulate sperm motility in teleosts but their mechanisms of action remain unclear. Preliminary results suggest that progestin upregulation of sperm motility in southern flounder and several other marine species is mediated through a sperm membrane progestin receptor with the characteristics of membrane progestin receptor alpha (mPRα, also known as Paqr7b). The hypothesis that mPRα has an important role in progestin regulation of southern flounder sperm motility and fertility was tested in the present study. The specific mPRα agonist, 10-ethenyl-19-norprogesterone (Org OD 02-0, 100nM), mimicked the stimulatory actions of the endogenous progestin, 17,20β, 21-trihydroxy-4-pregnen-3-one (20β-S, 100nM) on flounder sperm motility. The concentration of the mPRα protein on sperm plasma membranes was positively correlated to sperm motility as well as the responsiveness of sperm to progestin stimulation. Acute in vitro progestin treatment of sperm with high mPRα protein levels increased both sperm motility and fertilization success in strip spawning experiments. However, in vitro progestin treatments were ineffective on sperm with low receptor abundance. A single injection of the superactive gonadotropin-releasing hormone analog (LHRHa, 100μg/kg) increased sperm motility and fertilization success in strip spawning experiments 72h post-injection which was accompanied by an increase in mPRα protein concentrations on sperm plasma membranes. These results provide clear evidence that southern flounder sperm hypermotility is mediated through mPRα. Stimulatory G proteins, but not inhibitory G proteins, were identified in flounder sperm plasma membrane fractions. The finding that treatment of flounder sperm plasma membrane fractions with either 20β-S or Org OD 02-0 increases cAMP levels suggests progestins stimulate flounder sperm motility by activating an mPRα/stimulatory G protein/membrane adenylyl cyclase pathway. A similar mechanism has been identified in Atlantic croaker, suggesting that the signaling pathway mediated by mPRα in sperm is highly conserved in advanced teleosts. Collectively, our results indicate that progestin-stimulation of flounder sperm hypermotility and fertility is dependent on a sufficient concentration of mPRα which can be upregulated by in vivo LHRHa treatments. These findings potentially have practical applications for enhancing the fertility of male flounder broodstock.
authors: The University of Texas at Austin, Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA.
authors: Wenxian
authors: W
authors: Tan
authors: The University of Texas at Austin, Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA.
authors: Joseph
authors: J
authors: Aizen
authors: The University of Texas at Austin, Marine Science Institute, 750 Channel View Drive, Port Aransas, TX 78373, USA. Electronic address: peter.thomas@utexas.edu.
authors: Peter
authors: P
authors: Thomas
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003350:Cortodoxone / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005306:Fertilization / Q000187:drug effects*; D005432:Flounder / Q000502:physiology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007267:Injections; D008297:Male; D009653:Norprogesterones / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D009653:Norprogesterones; D011372:Progestins; D011980:Receptors, Progesterone; C030703:19-norprogesterone; D007987:Gonadotropin-Releasing Hormone; C051954:17,20,21-trihydroxy-4-pregnen-3-one; D000242:Cyclic AMP; D019205:GTP-Binding Protein alpha Subunits, Gs; D003350:Cortodoxone
keywords: Membrane progestin receptor alpha; Nongenomic progestin action; Southern flounder; Sperm fertility; Sperm hypermotility; Sperm motility