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  2. dl-Mandelic acid exhibits high sperm-immobilizing activity and low vaginal irritation: A potential non-surfactant spermicide for contraception

dl-Mandelic acid exhibits high sperm-immobilizing activity and low vaginal irritation: A potential non-surfactant spermicide for contraception

  • Biomed Pharmacother. 2020 Jun;126:110104. doi: 10.1016/j.biopha.2020.110104.
Minjie Xia 1 Mingjun Yang 1 Yuzhu Wang 1 Fang Tian 1 Jingying Hu 1 Wei Yang 1 Shimin Tao 1 Lu Lu 2 Xuncheng Ding 1 Shibo Jiang 3 Weihua Li 4
Affiliations

Affiliations

  • 1 Key Laboratory of Reproduction Regulation of National Health Commission (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, 200032, China.
  • 2 Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, 130 Dong An Rd., Xuhui District, Shanghai, 200032, China.
  • 3 Key Laboratory of Reproduction Regulation of National Health Commission (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, 200032, China; Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, 130 Dong An Rd., Xuhui District, Shanghai, 200032, China; Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA. Electronic address: shibojiang@fudan.edu.cn.
  • 4 Key Laboratory of Reproduction Regulation of National Health Commission (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, 200032, China. Electronic address: weihua.li@sippr.org.cn.
Abstract

dl-Mandelic acid (MA), an alpha-hydroxycarboxylic acid, has been widely used as an intermediate of pharmaceutical and fine chemicals. Here, we evaluated the sperm-immobilizing activity of MA and its safety profiles. Spermatozoon motility was assessed by computer-aided sperm analysis, the integrity of the plasma membrane and. mitochondrial potential was assessed using fluorescein isothiocyanate-pisum sativum agglutinin and JC-1, respectively. The local tolerance of the MA-containing gel formulation was evaluated using a rabbit vaginal irritation test. We found that MA inhibited sperm motility and movement patterns in a concentration-dependent manner. Within 20 s, MA-induced spermatozoa immobilization occurred with a minimum effective concentration and a median effective concentration of 0.86 and 0.54 mg/mL, respectively. Plasma membrane disruptions of MA-treated spermatozoa were relatively mild, but mitochondrial depolarization occurred. Histopathological examination showed that MA exposure did not exert obvious effects on the integrity of spermatozoa membrane structures and only caused slight irritation to the rabbit vaginal epithelium. The vaginal irritation scores of the vehicle control and the nonoxynol -9 gel control groups were 1.38 ± 0.65 and 7.88 ± 1.67, respectively (p < 0.01), whereas those of the MA gel groups at 10, 20, and 40 mg/mL were 1.69 ± 1.04, 2.98 ± 0.77, and 4.35 ± 1.04 with p values of >0.05, >0.05, and <0.05 (vs. vehicle control), respectively, which were within the clinically acceptable range (<8). Therefore, our results confirmed that MA exhibited significant sperm-immobilizing effects and caused mild plasma membrane injury, suggesting that it has potential for development as a future non-surfactant spermicide.

Keywords

Immobilization; Mandelic acid; Spermicide; Vaginal irritation.

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