β-Caryophyllene as putative male contraceptive: enhances spermatogenesis but not spermiogenesis in albino rats

Abstract

It is Cannabis-derived cannabinoid receptors type 2 (CB2R) agonist. CBR2 are expressed in germ cells within the testes. The aim of this study was to investigate the effect of b-Car on the male rat body weight, sex organ weight, sperm count, motility and morphology, and on the histology and the ultrastructure of the testes and the cauda epididymides. Moreover, we compared these effects with the results of the reversible infertility inducer: metronidazole (MTZ). Sexually mature male rats were divided into five groups that received intraperitoneal injections of 10 mg/kg b-Car, 40 mg/kg MTZ, distilled water, tween 80 in normal saline solution (10 % v/v), or did not receive any treatment for an experimental period of 30 days. Cauda epididymal sperm suspensions were used to assess the sperm count, motility, and morphology. Histological and ultrastructural studies were performed on testes and cauda epididymides. Treatment with b-Car (10 mg/kg, i.p.) significantly increased the final body weight, but did not affect the sex organ weight. It resulted in a significant decrease in cauda epididymal sperm count, percentages of motile sperms, and sperms with normal morphology. Nevertheless, it neither affected the histology nor the ultrastructure of the testes or the cauda epididymides of the treated rats. As a CB2R, b-Car could be a promising natural male contraceptive, because 30-day treatment with 10 mg/kg b-Car did not affect spermatogenesis but negatively affected spermiogenesis.

Natural Products with Potential for Nonhormonal Male Contraception

“…Notably, β-caryophyllene did not affect histology or ultrastructure of the testes or the cauda epididymis, and it appears to affect spermiogenesis but not spermatogenesis. The LD 50 > 5000 mg/kg in rats is promising for safety and tolerability, but the low bioavailability of β-caryophyllene could pose practical challenges for drug delivery in humans . β-Caryophyllene is highly lipophilic and has poor stability in hydrophilic media .…”

“…The LD 50 > 5000 mg/kg in rats is promising for safety and tolerability, but the low bioavailability of β-caryophyllene could pose practical challenges for drug delivery in humans. 44 β-Caryophyllene is highly lipophilic and has poor stability in hydrophilic media. 44 However, several studies have investigated delivery systems to overcome this challenge with regard to β-caryophyllene's possibilities as an anticancer agent.…”

“…44 β-Caryophyllene is highly lipophilic and has poor stability in hydrophilic media. 44 However, several studies have investigated delivery systems to overcome this challenge with regard to β-caryophyllene's possibilities as an anticancer agent. Di Sotto et al proposed a soy phosphatidylcholine (SPC) liposomal formulation to improve drug delivery and absorption.…”

Non-Hormonal Contraception

“…These receptors are commonly expressed in immune-related cells during active inflammation as well as in testicular germ cells. Male rats treated with β-caryophyllene had reduced sperm motility [121], abnormal sperm morphology, and reduced total sperm count [118].…”