Sperm utilize tumor necrosis factor alpha to shut down a 2-methoxyestradiol nongenomic pathway that accelerates oviductal egg transport in the rat

Abstract

The transport of oocytes or embryos throughout the oviduct to the implantation site in the uterus is defined as egg transport. In the rat, 2-methoxyestradiol (2ME) accelerates egg transport through the oviduct via a nongenomic pathway. Mating is known to shut down this 2ME pathway and then trigger an estradiol (E2) genomic pathway that accelerates egg transport. Here, we tested whether intrauterine insemination (IUI) and/or vaginocervical stimulation (VCS) shuts down the 2ME nongenomic pathway that accelerates egg transport, and if these mating components requires TNF-. Levels of TNF- and the mRNA for TNF- receptors were measured in the oviduct of IUI or VCS rats. The tissue distribution of TNF- receptors proteins, concentration of the mRNA for Catechol-O-methyl transferase (Comt) and 2ME were also analyzed in the oviduct. Finally, we assessed whether 2ME accelerates egg transport in IUI or VCS rats previously treated with the TNF- antagonist W9P9QY. Results show that IUI, but not VCS, increased TNF- and their receptors in the oviduct. IUI and VCS did not change the tissue distribution of TNF- receptors, however, both decreased the oviductal concentration of Comt and 2ME. IUI and VCS each blocked the 2ME-induced egg transport acceleration, however, only the IUI was antagonized by the TNF- antagonist. We concluded that IUI and VCS inhibit the 2ME nongenomic pathway that accelerates egg transport, however the vias of action are distinct, with a TNF- increase on spermatozoa presence being required for the shut down of the 2ME pathway.

Zeolite Nanoparticles Loaded with 2-Methoxystradiol as a Novel Drug Delivery System for the Prostate Cancer Therapy

“…Animals were euthanized and their tumors were excised, and a minor portion was fixed in cold 4% paraformaldehyde in PBS pH 7.4–7.6 and then processed for histological analysis according to Orostica et al [ 55 ]. The rest of the organ was cut into small (4–8 mm 2 ) pieces in Hanks’ solution and then the smooth muscle cells were mechanically removed from the rest of the tissue and treated with Collagenase, Type I (Invitrogen, Carlsbad, CA, USA) for 1 h to further disaggregation of the cells.…”