Yin Hang, Wang Xiang, Kim S Samuel, Chen Huifang, Tan Seang Lin, Gosden Roger G
Department of Obstetrics and Gynecology, McGill University, Royal Victoria Hospital, Montreal, QC H3A 1A1, Canada.
Hum Reprod. 2003 Jun;18(6):1165-72. doi: 10.1093/humrep/deg236.
A limited store of ovarian follicles is present at birth and its progressive decline during ageing is hastened by alkylating agents and ionizing radiation during treatment for cancer or autoimmune disease. Oligo- or azoospermia can arise for similar reasons in men. There is some experimental evidence showing that targeted gene deletion or drugs to produce hypogonadotrophism can protect germ cells from wastage. Another strategy for conserving fertility is to cryopreserve ovarian or testicular tissue for subsequent transplantation. To maximize gonadal function, it is desirable to preserve whole gonads for transplantation using vascular anastomosis.
We investigated this strategy in the rat model. All freshly isotransplanted ovaries (n = 8) survived and resumed follicle growth and secretion and, although ischaemia for 24 h at 4 degrees C did not disrupt ovarian function, the organs had fewer follicles. Four out of seven (57%) cryopreserved transplants survived for > or =60 days, were ovulatory and one pregnancy was established, but the ovarian reserve was compromised by fewer follicles. Ovarian allotransplants were vigorously rejected, even with moderate immunosuppression using cyclosporin A. On the other hand, only three out of seven (42%) fresh testicular isotransplants had active spermatogenesis, and none of the cryopreserved testes was functional.
The effects of gonadectomy in rats can be reversed by isotransplants, but the results are more successful with ovaries than testes, and allotransplants were never successful. Intact cryopreserved ovaries can be restored to function after transplantation with vascular anastomoses.
出生时卵巢卵泡储备有限，在癌症或自身免疫性疾病治疗期间，烷基化剂和电离辐射会加速其在衰老过程中的逐渐衰退。男性也可能因类似原因出现少精子症或无精子症。有一些实验证据表明，靶向基因缺失或产生性腺功能减退的药物可保护生殖细胞免于损耗。另一种保存生育能力的策略是冷冻保存卵巢或睾丸组织以供后续移植。为了使性腺功能最大化，期望使用血管吻合术保存整个性腺以供移植。
我们在大鼠模型中研究了这一策略。所有新鲜的同基因移植卵巢（n = 8）均存活，并恢复了卵泡生长和分泌，尽管在4℃下缺血24小时并未破坏卵巢功能，但这些器官中的卵泡数量减少。七例冷冻保存的移植卵巢中有四例（57%）存活超过或等于60天，具有排卵功能，且有一例成功受孕，但卵泡数量减少导致卵巢储备功能受损。卵巢异体移植即使使用环孢素A进行适度免疫抑制也会被强烈排斥。另一方面，七例新鲜的睾丸同基因移植中只有三例（42%）有活跃的精子发生，冷冻保存的睾丸均无功能。
大鼠性腺切除的影响可通过同基因移植逆转，但卵巢移植的结果比睾丸移植更成功，而异体移植从未成功。完整的冷冻保存卵巢在进行血管吻合移植后可恢复功能。
