An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when adm...An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when administered an intraperitoneal injection of 40 mg kg^?1.In the present study,hematoxylin and eosin staining,Western blot,immunofluorescence,and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses(20,30,and 40 mg kg^?1)on day 36 or a dose of 40 mg kg^?1 at different time points(0,9,18,27,36,and 63 days).The survival rate of the mice was 100%.When the mice were treated with 40 mg kg^?1 busulfan,dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36.In addition,the gene expressions of glial cell line-derived neurotrophic factor(GDNF),fibroblast growth factor 2(FGF2),chemokine(C-X-C Motif)ligand 12(CXCL12),and colony-stimulating factor 1(CSF1)were moderately increased by day 36.A 63-day,long-term observation showed the rare restoration of endogenous germ cells in the testes,suggesting that the potential period for SSC transplantation was between day 36 and day 63.Our results demonstrate that the administration of two intraperitoneal injections of busulfan(40 mg kg^?1 in total)at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.展开更多
Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg&...Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg·kg-1·d-1 in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 μm thickness, stained with H&E and analyzed microscopically. Results: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. Conclusion: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.展开更多
A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother.Several factors that influenced the success of the pregnancy in this...A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother.Several factors that influenced the success of the pregnancy in this case were analyzed.Favorable factors included:triple positive breast cancer[positive hormone receptors and positive human epidermal growth factor receptor 2],which is more hormosensitive and chemosensitive;absence of metastasis;correct endometrium preparation;and the patient's optimistic attitude and strict health habits.In contrast,the factors against success were:breast cancer;adjuvant breast cancer therapy gonadotoxicity;the age of the patient(>40-year-old);endometriosis;ovarian cyst;hydrosalpinx;submucosal fibroids and the respective associated surgery done for the above-mentioned pathology(all resolved prior to the embryo transfer);and a low quantity of ovules(low ovarian reserve)after ovarian stimulation.This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies,who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding.展开更多
We aimed to compare the sperm quality in different cancer types and benign diseases before gonadotoxic treatment,and assess the usage rate of cryopreserved sperm for assisted reproductive treatment(ART).This retrospec...We aimed to compare the sperm quality in different cancer types and benign diseases before gonadotoxic treatment,and assess the usage rate of cryopreserved sperm for assisted reproductive treatment(ART).This retrospective study was conducted at two university clinics between January 2008 and July 2018.A total of 545 patients suffering from cancer or benign diseases were included in the study.The pretreatment sperm analyses were based on the World Health Organization(WHO)guidelines.Patients with testicular malignancy(TM)showed a significantly lower sperm count(median[interquartile range]:18.7×10^(6)[5.3×10^(6)-43.0×10^(6)]ml^(-1);P=0.03)as well as total sperm count(42.4×10^(6)[13.3×10^(6)-108.5×10^(6)]per ejaculate;P=0.007)compared to other malignant and benign diseases.In addition,patients with nonseminomatous TM showed the lowest sperm count(14.3×10^(6)[6.0×10^(6)-29.9×10^(6)]ml^(-1),vs seminomas:16.5 x 106[4.6×10^(6)-20.3×10^(6)]ml^(-1);P=0.001).With reference to the WHO 2010 guidelines,approximately 48.0%of the patients with TM and 23.0%with hematological malignancies(HM)had oligozoospermia.During the observation period,only 29 patients(5.3%)used their frozen sperms for 48 ART cycles,resulting in 15 clinical pregnancies and 10 live births.The sperm quality varies with the type of underlying disease,with TM and HM patients showing the lowest sperm counts.Due to the observed low usage rate of cryopreserved sperm,further patient interviews and sperm analyses should be included in the routine oncologic protocols to avoid unnecessary storage expenses.However,sperm banking is worth the effort as it provides hope for men who cannot reproduce naturally after gonadotoxic treatment.展开更多
基金This study was supported by the National Natural Science Foundation of China(No.81571489,No.81671834,No.81671449 and No.81871110)the Frontier and Key Technology Innovation Special Foundation of Guangdong Province,China(No.2016B030230001)+3 种基金the Natural Science Foundation of Guangdong Province,China(No.2014A030310359,No.2016A030313229 and No.2015A030313013)the Science and Technology Planning Project of Guangdong Province,China(No.2016A020214004)the Health Care Collaborative Innovation Foundation Major Projects of Guangzhou City,Guangdong Province,China(No.201604020189)the Youth Teacher Training Project of Sun Yat-sen University(No.17ykpy68 and No.18ykpy09).
文摘An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell(SSC)transplantation.Busulfan has been commonly used to develop such a model,but 30%–87%of mice die when administered an intraperitoneal injection of 40 mg kg^?1.In the present study,hematoxylin and eosin staining,Western blot,immunofluorescence,and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses(20,30,and 40 mg kg^?1)on day 36 or a dose of 40 mg kg^?1 at different time points(0,9,18,27,36,and 63 days).The survival rate of the mice was 100%.When the mice were treated with 40 mg kg^?1 busulfan,dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36.In addition,the gene expressions of glial cell line-derived neurotrophic factor(GDNF),fibroblast growth factor 2(FGF2),chemokine(C-X-C Motif)ligand 12(CXCL12),and colony-stimulating factor 1(CSF1)were moderately increased by day 36.A 63-day,long-term observation showed the rare restoration of endogenous germ cells in the testes,suggesting that the potential period for SSC transplantation was between day 36 and day 63.Our results demonstrate that the administration of two intraperitoneal injections of busulfan(40 mg kg^?1 in total)at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
文摘Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg·kg-1·d-1, 400 mg·kg-1·d-1 or 800 mg·kg-1·d-1 in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5 μm thickness, stained with H&E and analyzed microscopically. Results: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. Conclusion: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility.
基金Supported by grants from the Instituto CarlosⅢ,Nos.PI11/01377 and ISCⅢ-RETICRD12/0036/0029Government of Catalonia,No.2017SGR-1014
文摘A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother.Several factors that influenced the success of the pregnancy in this case were analyzed.Favorable factors included:triple positive breast cancer[positive hormone receptors and positive human epidermal growth factor receptor 2],which is more hormosensitive and chemosensitive;absence of metastasis;correct endometrium preparation;and the patient's optimistic attitude and strict health habits.In contrast,the factors against success were:breast cancer;adjuvant breast cancer therapy gonadotoxicity;the age of the patient(>40-year-old);endometriosis;ovarian cyst;hydrosalpinx;submucosal fibroids and the respective associated surgery done for the above-mentioned pathology(all resolved prior to the embryo transfer);and a low quantity of ovules(low ovarian reserve)after ovarian stimulation.This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies,who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding.
文摘We aimed to compare the sperm quality in different cancer types and benign diseases before gonadotoxic treatment,and assess the usage rate of cryopreserved sperm for assisted reproductive treatment(ART).This retrospective study was conducted at two university clinics between January 2008 and July 2018.A total of 545 patients suffering from cancer or benign diseases were included in the study.The pretreatment sperm analyses were based on the World Health Organization(WHO)guidelines.Patients with testicular malignancy(TM)showed a significantly lower sperm count(median[interquartile range]:18.7×10^(6)[5.3×10^(6)-43.0×10^(6)]ml^(-1);P=0.03)as well as total sperm count(42.4×10^(6)[13.3×10^(6)-108.5×10^(6)]per ejaculate;P=0.007)compared to other malignant and benign diseases.In addition,patients with nonseminomatous TM showed the lowest sperm count(14.3×10^(6)[6.0×10^(6)-29.9×10^(6)]ml^(-1),vs seminomas:16.5 x 106[4.6×10^(6)-20.3×10^(6)]ml^(-1);P=0.001).With reference to the WHO 2010 guidelines,approximately 48.0%of the patients with TM and 23.0%with hematological malignancies(HM)had oligozoospermia.During the observation period,only 29 patients(5.3%)used their frozen sperms for 48 ART cycles,resulting in 15 clinical pregnancies and 10 live births.The sperm quality varies with the type of underlying disease,with TM and HM patients showing the lowest sperm counts.Due to the observed low usage rate of cryopreserved sperm,further patient interviews and sperm analyses should be included in the routine oncologic protocols to avoid unnecessary storage expenses.However,sperm banking is worth the effort as it provides hope for men who cannot reproduce naturally after gonadotoxic treatment.
