Accelerated follicle depletion in vitro and in vivo in Sprague-Dawley rats using the combination of 4-vinylcyclohexene diepoxide and triptolide.
Rodent pests cause major damage to the world's agricultural crops and food stores. Rodenticides used since World War II did not lead to sustained reduction of rodent populations, and so fertility control is becoming attractive because rats reproduce with great efficiency. Chemical acceleration of ovarian failure via oral dosing also would improve management of rat pest populations. The chemical 4-vinylcyclohexene diepoxide (VCD) is orally efficacious, causing depletion of nonregenerating primordial ovarian follicles of Sprague-Dawley rats. However, to cause rapid reduction in pups in the first breeding cycle after dosing, all stages of ovarian follicle development must be targeted. To achieve this goal, the Chinese herb triptolide was tested because it can precipitate apoptosis and deplete growing follicles. The impact of triptolide was tested in cultured postnatal day 4 Sprague-Dawley rat pup ovaries. Triptolide at 5 nM caused 100% primordial, primary, and secondary follicle depletion after 8 days of culture, compared to 38% follicle depletion caused by VCD at 30 microM. Next, a palatable rat bait was developed, containing 1% VCD with increasing concentrations of triptolide at 25, 50, and 100 microg/kg body weight. Rats ate an average 3-6% of their body weight/day over 15 feeding days. Two days after the end of baiting, rats were euthanized to conduct necropsies and collect ovaries to count all follicular stages and corpora lutea. At 50 microg triptolide/kg body weight, there was significant reduction of all follicular stages; primordial follicles were 50% lower, secondary follicles were 64% lower, antral follicles were 80% lower, and there were no corpora lutea. These results suggest that combining VCD and triptolide in an oral bait leads to significantly compromised rat ovarian function and reduced ovulations, and is likely to reduce pup production.
SenesTech, Inc., Flagstaff, Arizona 86004, USA. Cheryl.Dyer@senestech.com
Cheryl A
CA
Dyer
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Stefanie
S
Raymond-Whish
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Shawn
S
Schmuki
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Theresa
T
Fisher
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Brandy
B
Pyzyna
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Aaron
A
Bennett
SenesTech, Inc., Flagstaff, Arizona 86004, USA.
Loretta P
LP
Mayer
D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000494:pharmacology*; D053138:Cyclohexenes / Q000008:administration & dosage / Q000494:pharmacology*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006080:Ovarian Follicle / Q000187:drug effects*; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D011155:Population Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D003271:Contraceptive Agents, Female; D053138:Cyclohexenes; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D014753:Vinyl Compounds; C001899:triptolide; C012606:4-vinyl-1-cyclohexene dioxide