Tsuyoshi Hideaki, Orisaka Makoto, Fukuda Shin, Hattori Katsushige, Tsang Benjamin K, Yoshida Yoshio
Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
Steroids. 2015 Jan;93:1-7. doi: 10.1016/j.steroids.2014.10.010. Epub 2014 Nov 20.
Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy.
生育力下降是年轻女性因淋巴瘤、白血病和其他恶性肿瘤接受化疗的主要长期后果之一。我们使用雌性大鼠模型研究了第四代孕激素地诺孕素是否以及如何调节性腺毒性化疗后生育力的下降。对雌性大鼠给予环磷酰胺，同时给予或不给予GnRH激动剂以及不同浓度的地诺孕素，持续20天。在第29天处死动物，通过组织学方法计数卵巢中原始卵泡、窦前卵泡和窦状卵泡的数量。用无菌盐溶液（作为对照）、环磷酰胺、环磷酰胺加GnRH激动剂以及环磷酰胺加地诺孕素处理的大鼠也与雄性大鼠交配，以评估它们的生育力和妊娠结局。环磷酰胺显著减少了原始卵泡的数量，而地诺孕素抑制了化疗诱导的原始卵泡池的耗竭。尽管单独接受环磷酰胺处理的大鼠未能产下活仔，但地诺孕素联合处理改善了受试大鼠的妊娠结局。地诺孕素对化疗诱导的卵巢损伤和生育力下降的保护作用与GnRH激动剂相当。目前的结果表明，地诺孕素与化疗联合使用可能是一种有用的策略，可用于保护面临性腺毒性化疗的绝经前女性的卵巢功能和生育力。
