title: Generation of haploid spermatids with fertilization and development capacity from human spermatogonial stem cells of cryptorchid patients.
abstract: Generation of functional spermatids from azoospermia patients is of unusual significance in the treatment of male infertility. Here, we report an efficient approach to obtain human functional spermatids from cryptorchid patients. Spermatogonia remained whereas meiotic germ cells were rare in cryptorchid patients. Expression of numerous markers for meiotic and postmeiotic male germ cells was enhanced in human spermatogonial stem cells (SSCs) of cryptorchidism patients by retinoic acid (RA) and stem cell factor (SCF) treatment. Meiotic spreads and DNA content assays revealed that RA and SCF induced a remarkable increase of SCP3-, MLH1-, and CREST-positive cells and haploid cells. Single-cell RNA sequencing analysis reflected distinct global gene profiles in embryos derived from round spermatids and nuclei of somatic cells. Significantly, haploid spermatids generated from human SSCs of cryptorchid patients possessed fertilization and development capacity. This study thus provides an invaluable source of autologous male gametes for treating male infertility in azoospermia patients.
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ping
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China.
authors.forename: Ruhui
authors.initials: R
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai 200001, China. Electronic address: lizhengboshi@163.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai Human Sperm Bank, Shanghai Institute of Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Linshan Road, Shanghai 200135, China; State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai 200127, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai 200001, China. Electronic address: zupinghe@sjtu.edu.cn.
authors.forename: Zuping
authors.initials: Z
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003456:Cryptorchidism / Q000473:pathology*; D004268:DNA-Binding Proteins; D005306:Fertilization; D006238:Haploidy; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D013087:Spermatids / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013091:Spermatogenesis; D013093:Spermatogonia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C502810:SS18L1 protein, human; C490060:SYCP3 protein, human; D019089:Stem Cell Factor; D015534:Trans-Activators; D014212:Tretinoin; D000070957:MutL Protein Homolog 1