Manivannan Boomi, Mittal Ruchi, Goyal Shipra, Ansari Abdul S, Lohiya Nirmal K
Department of Zoology, Centre for Advanced Studies, University of Rajasthan, Jaipur 302004, India.
Asian J Androl. 2009 Sep;11(5):583-99. doi: 10.1038/aja.2009.25. Epub 2009 Aug 3.
The contraceptive efficacy of Carica papaya seeds after short-term evaluation has been well established. We have examined the safety and mechanism of contraception in rats after long-term treatment with the methanol subfraction (MSF) of C. papaya seeds. The test substance was administered orally to the male albino rats (n = 40) at 50 mg per kg body weight each day for 360 days. Control animals (n = 40) received olive oil as a vehicle. Recovery was assessed up to 120 days after treatment withdrawal. Sperm parameters, serum testosterone levels, fertility, histology and ultrastructure of the testis, haematology and serum clinical chemistry were evaluated to establish the safety and efficacy of the test substance. Safety of long-term treatment was evidenced by unaltered health status, organ weight, haematology and clinical chemistry, and by an increase in body weight. The mechanism of contraception was shown by reduction in nuclear and cytoplasmic volume, normal nuclear characteristics and vacuolization in the cytoplasmic organelles of the Sertoli cells, as well as nuclear degeneration in spermatocytes and spermatids indicating disturbed spermatogenesis. Leydig cells were normal. Initial effects were observed in Sertoli cells at 60 days of treatment. Spermatocytes and spermatids were affected after 120-240 days of treatment. A significant decline in sperm count and viability, total inhibition of sperm motility, increased numbers of sperm abnormalities, normal serum testosterone levels and 100% sterility were evident after 60 days of treatment. All the altered parameters, including percent fertility, were restored to control level 120 days after treatment withdrawal. It is concluded that the MSF is safe for long-term treatment and the mechanism of contraception is shown by its effect on spermatid differentiation in the testis, possibly mediated by the Sertoli cell factors.
番木瓜籽在短期评估后的避孕效果已得到充分证实。我们研究了番木瓜籽甲醇亚组分（MSF）长期治疗大鼠后的安全性和避孕机制。将受试物质以每千克体重50毫克的剂量口服给予雄性白化大鼠（n = 40），持续360天。对照动物（n = 40）接受橄榄油作为赋形剂。在停药后长达120天评估恢复情况。评估精子参数、血清睾酮水平、生育力、睾丸的组织学和超微结构、血液学和血清临床化学，以确定受试物质的安全性和有效性。长期治疗的安全性通过健康状况、器官重量、血液学和临床化学未改变以及体重增加得以证明。避孕机制表现为支持细胞的细胞核和细胞质体积减小、细胞核特征正常以及细胞质细胞器空泡化，同时精母细胞和精子细胞的细胞核变性，表明精子发生受到干扰。睾丸间质细胞正常。在治疗60天时在支持细胞中观察到初始效应。在治疗120 - 240天后精母细胞和精子细胞受到影响。治疗60天后精子数量和活力显著下降、精子运动完全抑制、精子异常数量增加、血清睾酮水平正常以及100%不育明显。所有改变的参数，包括生育力百分比，在停药120天后恢复到对照水平。结论是，MSF长期治疗是安全的，其避孕机制表现为对睾丸中精子细胞分化的影响，可能由支持细胞因子介导。
