Delta and kappa opioid receptors on mouse sperm cells: Expression, localization and involvement on in vitro fertilization

Reprod Toxicol. 2020 Apr:93:211-218. doi: 10.1016/j.reprotox.2020.02.013. Epub 2020 Mar 4.

Abstract

The endogenous opioid peptides have been reported to be involved in the regulation of reproductive physiology. Many of the studies conclude with sentences around the harmful effect of opioids in male fertility but, actually, there is only one study regarding the real fertility potential of spermatozoa that have been exposed to mu specific opioids. The aim of the present study was to see if the modulation of delta (OPRD1) and kappa (OPRK1) opioid receptors in mouse sperm during capacitation was able to vary the embryo production after in vitro fertilization (IVF). The presence of OPRD1 and OPRK1 in mouse mature spermatozoa was analyzed by RT-PCR and immunofluorescence. Incubating the sperm with, on one hand, the delta specific agonist DPDPE and/or antagonist naltrindole, and, on the other hand, the kappa specific agonist U-50488 and antagonist nor-binaltorphimine, we analyzed the involvement of OPRD1 and OPRK1 on IVF and preimplantational embryo development. We verified the presence of OPRD1 and OPRK1 in mouse mature spermatozoa, not only at the mRNA level but also at protein level. Moreover, the sperm incubation with DPDPE, before the IVF, had an effect on the fertilization rate of sperm and reduced the number of reached blastocysts, which was reverted by naltrindole. Instead, the use of the kappa agonist U-50488 and the antagonist nor-binaltophimine did not have any effect on the amount and the quality of the achieved blastocysts. Although nowadays the pure delta or kappa opioid ligands are not used for the clinic, clinical trials are being conducted to be used in the near future, so it would be interesting to know if the modulation of these receptors in sperm would generate any consequence in relation to fertilization capacity.

Keywords: Embryo; IVF; Opioid; Sperm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology
  • Animals
  • Blastocyst / physiology
  • Embryo, Mammalian
  • Embryonic Development
  • Enkephalin, D-Penicillamine (2,5)- / pharmacology
  • Fertilization in Vitro*
  • Male
  • Mice
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oocytes / physiology
  • Receptors, Opioid, delta / agonists
  • Receptors, Opioid, delta / antagonists & inhibitors
  • Receptors, Opioid, delta / genetics
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, kappa / genetics
  • Receptors, Opioid, kappa / metabolism*
  • Sperm Capacitation
  • Spermatozoa / physiology*

Substances

  • DOR-1 protein, mouse
  • Narcotic Antagonists
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Enkephalin, D-Penicillamine (2,5)-
  • naltrindole