KaydedilenlerDerginizi ekleyin

Dergiler / Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi / 2026 / Volume: 10 Issue: 2

Embryonic Testis Development, Anatomy and the Role of Spermatogonial Stem Cells in Spermatogenesis

Vahit Ağır(SELCUK UNIVERSITY)0000-0001-6271-6088
Mustafa Numan Bucak0000-0002-2955-8599
Sayfa
—
Yayın Tarihi
2025-08-30
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Recent advances in SSC isolation, culture, and transplantation have highlighted their potential in both regenerative and reproductive applications, although significant challenges remain in maintaining their viability and purity during manipulation.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Spermatogenesis is a highly coordinated process that ensures the continuous production of spermatozoa in adult males.
📊
Temel Bulgular & Veri:This process originates from spermatogonial stem cells (SSCs) located in the basal compartment of the seminiferous tubules.
💡
Sonuç & Katkı:Recent advances in SSC isolation, culture, and transplantation have highlighted their potential in both regenerative and reproductive applications, although significant challenges remain in maintaining their viability and purity during manipulation.
🔬Tür:Laboratuvar & Saha Deneyi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Spermatogenesis · Spermatogonial stem cells (SSCs) · Testosterone

Abstract

Spermatogenesis is a highly coordinated process that ensures the continuous production of spermatozoa in adult males. This process originates from spermatogonial stem cells (SSCs) located in the basal compartment of the seminiferous tubules. SSCs are unique among adult stem cells in that they not only maintain the stem cell pool through self-renewal but also give rise to differentiated germ cells that contribute genetically to the next generation. Spermatogenesis involves sequential stages of proliferation, meiosis, and morphological maturation, supported by Sertoli cells and regulated by endocrine signals from the hypothalamic pituitary gonadal axis. In this context, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play essential roles by acting on Sertoli and Leydig cells, respectively, to sustain the microenvironment required for germ cell development. Leydig cell-derived testosterone exerts its effects through classical and non-classical pathways, modulating gene expression and cellular interactions critical for spermatogenesis. Furthermore, spermatozoa undergo functional maturation during epididymal transit, acquiring motility and fertilizing capacity. Understanding the biology of SSCs and the molecular and hormonal mechanisms controlling spermatogenesis has profound implications for reproductive medicine, infertility treatment, and the conservation of endangered species. Recent advances in SSC isolation, culture, and transplantation have highlighted their potential in both regenerative and reproductive applications, although significant challenges remain in maintaining their viability and purity during manipulation.

🔖

Bu Makaleye Atıf Yap

Ağır, V., Bucak, M. N. (2025). Embryonic Testis Development, Anatomy and the Role of Spermatogonial Stem Cells in Spermatogenesis. Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, Volume: 10 Issue: 2. https://doi.org/10.51754/cusbed.1750799

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (163)

  1. Abou-Haila, A., & Tulsiani, D. R. P. (2000). Mammalian Sperm Acrosome: Formation, Contents, and Function. Archives of Biochemistry and Biophysics, 379(2), 173-182. DOI:10.1006/abbi.2000.1880
  2. AL-Mamari, S. A. (2023). Anatomy of the Scrotum and Testicles. In Urogenital Trauma: A Practical Guide (pp. 355-370). Springer Nature Singapore. DOI:10.1007/978-981-99-6171-9_42
  3. Amann, R. P. (1989). Structure and Function of the Normal Testis and Epididymis. Journal of the American College of Toxicology, 8(3), 457-471. DOI:10.3109/10915818909014532
  4. Ariyaratne, H. B. S., & Chamindrani Mendis-Handagama, S. M. L. (2000). Changes in the Testis Interstitium of Sprague Dawley Rats from Birth to Sexual Maturity1. Biology of Reproduction, 62(3), 680-690. DOI:10.1095/biolreprod62.3.680
  5. Ariza, L., Carmona, R., Cañete, A., Cano, E., & Muñoz-Chápuli, R. (2016). Coelomic epithelium-derived cells in visceral morphogenesis. Developmental Dynamics, 245(3), 307-322. DOI:10.1002/dvdy.24373
  6. Auman, H. J., Nottoli, T., Lakiza, O., Winger, Q., Donaldson, S., & Williams, T. (2002). Transcription factor AP-2γ is essential in the extra-embryonic lineages for early postimplantation development. Development, 129(11), 2733-2747. DOI:10.1242/dev.129.11.2733
  7. Bagci, H., & Fisher, A. G. (2013). DNA demethylation in pluripotency and reprogramming: the role of tet proteins and cell division. Cell Stem Cell, 13(3), 265-269.
  8. Balhorn, R. (2007). The protamine family of sperm nuclear proteins. Genome Biology, 8(9), 227. DOI:10.1186/gb-2007-8-9-227
  9. Bandiera, R., Vidal, V. P., Motamedi, F. J., Clarkson, M., Sahut-Barnola, I., von Gise, A., Pu, W. T., Hohenstein, P., Martinez, A., & Schedl, A. (2013). WT1 maintains adrenal-gonadal primordium identity and marks a population of AGP-like progenitors within the adrenal gland. Developmental cell, 27(1), 5-18.
  10. Bao, S., Leitch, H. G., Gillich, A., Nichols, J., Tang, F., Kim, S., Lee, C., Zwaka, T., Li, X., & Surani, M. A. (2012). The germ cell determinant Blimp1 is not required for derivation of pluripotent stem cells. Cell Stem Cell, 11(1), 110-117. DOI:10.1016/j.stem.2012.02.023
  11. Beddington, R. S., & Robertson, E. J. (1999). Axis development and early asymmetry in mammals. Cell, 96(2), 195-209.
  12. Borjigin, U., Davey, R., Hutton, K., & Herrid, M. (2010). Expression of promyelocytic leukaemia zinc-finger in ovine testis and its application in evaluating the enrichment efficiency of differential plating. Reproduction, Fertility and Development, 22(5), 733-742.
  13. Brandenburger, T., Strehler, E. E., Filoteo, A. G., Caride, A. J., Aumüller, G., Post, H., Schwarz, A., & Wilhelm, B. (2011). Switch of PMCA4 splice variants in bovine epididymis results in altered isoform expression during functional sperm maturation. Journal of Biological Chemistry, 286(10), 7938-7946. DOI:10.1074/jbc.M110.142836
  14. Braun, R. E. (2001). Packaging paternal chromosomes with protamine. Nature Genetics, 28(1), 10-12. DOI:10.1038/ng0501-10
  15. Breton, S., Ruan, Y. C., Park, Y.-J., & Kim, B. (2016). Regulation of epithelial function, differentiation, and remodeling in the epididymis. Asian journal of andrology, 18(1), 3. DOI:10.4103/1008-682X.165946
  16. Caballero, J., Frenette, G., D'Amours, O., Belleannée, C., Lacroix‐Pepin, N., Robert, C., & Sullivan, R. (2012). Bovine sperm raft membrane associated Glioma Pathogenesis‐Related 1‐like protein 1 (GliPr1L1) is modified during the epididymal transit and is potentially involved in sperm binding to the zona pellucida. Journal of cellular physiology, 227(12), 3876-3886. DOI:10.1002/jcp.24099.
  17. Caballero, J., Frenette, G., & Sullivan, R. (2011). Post testicular sperm maturational changes in the bull: important role of the epididymosomes and prostasomes. Veterinary medicine international, 2011. DOI:10.4061/2011/757194.
  18. Caires, K. C., de Avila, J., & McLean, D. J. (2009). Vascular endothelial growth factor regulates germ cell survival during establishment of spermatogenesis in the bovine testis. Reproduction, 138(4), 667.
  19. Carré, G.-A., & Greenfield, A. (2016). The gonadal supporting cell lineage and mammalian sex determination: the differentiation of sertoli and granulosa cells. Molecular Mechanisms of Cell Differentiation in Gonad Development, 47-66. DOI:10.1007/978-3-319-31973-5_3
  20. Casarini, L., & Crépieux, P. (2019). Molecular mechanisms of action of FSH. Frontiers in endocrinology, 10, 305. DOI:10.3389/fendo.2019.00305.
  21. Chang, C., Chen, Y.-T., Yeh, S.-D., Xu, Q., Wang, R.-S., Guillou, F., Lardy, H., & Yeh, S. (2004). Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proceedings of the National Academy of Sciences, 101(18), 6876-6881. DOI:10.1073/pnas.0307306101.
  22. Cheng, C. Y., & Mruk, D. D. (2002). Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiological reviews, 82(4), 825-874. DOI:10.1152/physrev.00009.2002
  23. Chia, N.-Y., Chan, Y.-S., Feng, B., Lu, X., Orlov, Y. L., Moreau, D., Kumar, P., Yang, L., Jiang, J., & Lau, M.-S. (2010). A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity. Nature, 468(7321), 316-320. DOI:10.1038/nature09531
  24. Chu, L.-F., Surani, M. A., Jaenisch, R., & Zwaka, T. P. (2011). Blimp1 expression predicts embryonic stem cell development in vitro. Current Biology, 21(20), 1759-1765. Clermont, Y. (1972). Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiological Reviews, 52(1), 198-236. DOI:10.1152/physrev.1972.52.1.198
  25. Connell, S. M. (2024). Aristotle on Memory and Emotion in Human and Non-human Animals. Memory and Emotions in Antiquity, acadcmia. edu.
  26. Culty, M. (2009). Gonocytes, the forgotten cells of the germ cell lineage. Birth Defects Research Part C: Embryo Today: Reviews, 87(1), 1-26. DOI:10.1002/bdrc.20142
  27. Cyr, D. G., Gregory, M., Dubé, É., Dufresne, J., Chan, P. T., & Hermo, L. (2007). Orchestration of occludins, claudins, catenins and cadherins as players involved in maintenance of the blood‐epididymal barrier in animals and humans. Asian journal of andrology, 9(4), 463-475. DOI:10.1111/j.1745-7262.2007.00308.x
  28. Dalgaard, M., Pilegaard, K., & Ladefoged, O. (2002). In Utero Exposure to Diethylstilboestrol or 4‐n‐Nonylphenol in Rats: Number of Sertoli Cells, Diameter and Length of Seminiferous Tubules Estimated by Stereological Methods. Pharmacology & toxicology, 90(2), 59-65. DOI:10.1034/j.1600-0773.2002.900202.x
  29. de Barros, F. R. O., Giassetti, M. I., & Visintin, J. A. (2012). Spermatogonial stem cells and animal transgenesis. Innovations in biotechnology. 1st ed. Rijeka: InTech, 303-318.
  30. De Rooıj, D. G., & Russell, L. D. (2000). All you wanted to know about spermatogonia but were afraid to ask. Journal of andrology, 21(6), 776-798. DOI:10.1002/j.1939-4640.2000.tb03408.x
  31. DeFalco, T., Potter, S. J., Williams, A. V., Waller, B., Kan, M. J., & Capel, B. (2015). Macrophages contribute to the spermatogonial niche in the adult testis. Cell reports, 12(7), 1107-1119. http://doi.org/10.1016/j.devcel.2013.09.003.
  32. Eddy, E. M., Toshimori, K., & O'Brien, D. A. (2003). Fibrous sheath of mammalian spermatozoa. Microscopy Research and Technique, 61(1), 103-115. DOI:10.1002/jemt.10320
  33. Farkaš, R. (2015). Apocrine secretion: new insights into an old phenomenon. Biochimica Et Biophysica Acta (BBA)-General Subjects, 1850(9), 1740-1750.
  34. Fawcett, D. W. (1975). The mammalian spermatozoon. Developmental Biology, 44(2), 394-436. DOI:10.1016/0012-1606(75)90411-X
  35. Fix, C., Jordan, C., Cano, P., & Walker, W. H. (2004). Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells. Proceedings of the National Academy of Sciences, 101(30), 10919-10924. DOI:10.1073/pnas.0404278101
  36. Frenette, G., Légaré, C., Saez, F., & Sullivan, R. (2005). Macrophage migration inhibitory factor in the human epididymis and semen. Molecular human reproduction, 11(8), 575-582. DOI:10.1093/molehr/gah197
  37. Frenette, G., & Sullivan, R. (2001). Prostasome‐like particles are involved in the transfer of P25b from the bovine epididymal fluid to the sperm surface. Molecular Reproduction and Development: Incorporating Gamete Research, 59(1), 115-121. DOI:10.1002/mrd.1013
  38. Garner, D., & Hafez, E. (2000). Spermatozoa and seminal plasma. Reproduction in farm animals, 96-109. DOI:10.1002/9781119265306.ch7
  39. Ge, R.-S., Dong, Q., Sottas, C. M., Chen, H., Zirkin, B. R., & Hardy, M. P. (2005). Gene expression in rat Leydig cells during development from the progenitor to adult stage: a cluster analysis. Biology of reproduction, 72(6), 1405-1415. DOI:10.1095/biolreprod.104.037499
  40. Gonen, N., & Lovell-Badge, R. (2019). Chapter Eight - The regulation of Sox9 expression in the gonad. In B. Capel (Ed.), Current Topics in Developmental Biology (Vol. 134, pp. 223-252). Academic Press. DOI:10.1016/bs.ctdb.2019.01.004
  41. Gregory, M., & Cyr, D. G. (2014). The blood-epididymis barrier and inflammation. Spermatogenesis, 4(2), e979619. DOI:10.4161/21565562.2014.979619
  42. Griswold, M. D. (1998). The central role of Sertoli cells in spermatogenesis. Seminars in Cell & Developmental Biology, 9(4), 411-416. DOI:10.1006/scdb.1998.0203
  43. Griswold, M. D. (2016). Spermatogenesis: The Commitment to Meiosis. Physiological Reviews, 96(1), 1-17. DOI:10.1152/physrev.00013.2015
  44. Guraya, S. S. (2012). Biology of spermatogenesis and spermatozoa in mammals. Springer Science & Business Media.
  45. Günesdogan, U., Magnúsdóttir, E., & Surani, M. A. (2014). Primoridal germ cell specification: a context-dependent cellular differentiation event. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1657), 20130543. DOI:10.1098/rstb.2013.0543
  46. Hafez, E. S. E., & Hafez, B. (2013). Reproduction in farm animals. John Wiley & Sons.
  47. Hamra, F. K., Schultz, N., Chapman, K. M., Grellhesl, D. M., Cronkhite, J. T., Hammer, R. E., & Garbers, D. L. (2004). Defining the spermatogonial stem cell. Developmental biology, 269(2), 393-410. DOI:10.1016/j.ydbio.2004.01.027
  48. Hanayama, R., Tanaka, M., Miwa, K., Shinohara, A., Iwamatsu, A., & Nagata, S. (2002). Identification of a factor that links apoptotic cells to phagocytes. Nature, 417(6885), 182-187. DOI:10.1038/417182a
  49. Hassa O, A. R. (2003). Embriyoloji. Yorum Basın Yayın Sanayi Ltd Şti, Ankara, 133–134.
  50. Hauser, F., Cazzamali, G., Williamson, M., Park, Y., Li, B., Tanaka, Y., Predel, R., Neupert, S., Schachtner, J., Verleyen, P., & Grimmelikhuijzen, C. J. P. (2008). A genome-wide inventory of neurohormone GPCRs in the red flour beetle Tribolium castaneum. Frontiers in Neuroendocrinology, 29(1), 142-165. DOI:10.1016/j.yfrne.2007.10.003
  51. Hermo, L., & Robaire, B. (2002). Epididymal cell types and their functions. In The epididymis: from molecules to clinical practice (pp. 81-102). Springer. DOI:10.1007/978-1-4615-0679-9_5
  52. Hess, R. A., & de Franca, L. R. (2008). Spermatogenesis and Cycle of the Seminiferous Epithelium. In C. Y. Cheng (Ed.), Molecular Mechanisms in Spermatogenesis (pp. 1-15). Springer New York. DOI:10.1007/978-0-387-09597-4_1
  53. Hofmann, M.-C., Braydich-Stolle, L., & Dym, M. (2005). Isolation of male germ-line stem cells; influence of GDNF. Developmental biology, 279(1), 114-124. DOI:10.1016/j.ydbio.2004.12.006
  54. Holdcraft, R. W., & Braun, R. E. (2004). Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development, 131(2), 459-467. DOI:10.1242/dev.00957
  55. Hu, Y.-C., Okumura, L. M., & Page, D. C. (2013). Gata4 is required for formation of the genital ridge in mice. PLoS Genet, 9(7), e1003629. DOI:10.1371/journal.pgen.1003629
  56. Huang, W., Eum, S. Y., András, I. E., Hennig, B., & Toborek, M. (2009). PPARα and PPARγ attenuate HIV‐induced dysrégulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities. The FASEB Journal, 23(5), 1596-1606.
  57. Hummitzsch, K., Irving-Rodgers, H. F., Schwartz, J., & Rodgers, R. J. (2019). Chapter 4 - Development of the Mammalian Ovary and Follicles. In P. C. K. Leung & E. Y. Adashi (Eds.), The Ovary (Third Edition) (pp. 71-82). Academic Press. DOI:10.1016/B978-0-12-813209-8.00004-2
  58. Irie, N., Tang, W. W., & Surani, M. A. (2014). Germ cell specification and pluripotency in mammals: a perspective from early embryogenesis. Reproductive medicine and biology, 13(4), 203-215. DOI:10.1007/s12522-014-0184-2
  59. Ishii, M., Kanai, Y., Kanai-Azuma, M., Tajima, Y., Wei, T. T., Kidokoro, T., Sanai, Y., Kurohmaru, M., & Hayashi, Y. (2005). Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis. Anatomy and embryology, 209(6), 485-494. DOI:10.1007/s00429-005-0463-0
  60. Ito, M., Yokouchi, K., Yoshida, K., Kano, K., Naito, K., Miyazaki, J. I., & Tojo, H. (2006). Investigation of the fate of Sry‐expressing cells using an in vivo Cre/loxP system. Development, growth & differentiation, 48(1), 41-47. DOI:10.1111/j.1440-169X.2006.00844.x
  61. Jin, M., Fujiwara, E., Kakiuchi, Y., Okabe, M., Satouh, Y., Baba, S. A., Chiba, K., & Hirohashi, N. (2011). Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization. Proceedings of the National Academy of Sciences, 108(12), 4892-4896. DOI:10.1073/pnas.1018202108 Joshi, C. S., Suryawanshi, A. R., Khan, S. A., Balasinor, N. H., & Khole, V. V. (2013). Liprin α3: a putative estrogen regulated acrosomal protein. Histochemistry and cell biology, 139(4), 535-548. DOI:10.1007/s00418-012-1044-y
  62. Jost, A. (1947). Recherches sur la differentiation de embryon delapin. III. Arch. Anat. Microscop. Morphol. Exp, 36, 271–315.
  63. Jost, A., Vigier, B., PrÉPin, J., & Perchellet, J. P. (1973). Studies on sex differentiation in mammals. Proceedings of the 1972 Laurentian Hormone Conference, DOI:10.1016/B978-0-12-571129-6.50004-X
  64. Kanatsu-Shinohara, M., & Shinohara, T. (2013). Spermatogonial Stem Cell Self-Renewal and Development. Annual review of cell and developmental biology, 29(Volume 29, 2013), 163-187. DOI:10.1146/annurev-cellbio-101512-122353
  65. Karkanaki, A., Praras, N., Katsikis, I., Kita, M., & Panidis, D. (2007). Is the Y chromosome all that is required for sex determination? Hippokratia, 11(3), 120-123.
  66. Katoh-Fukui, Y., Miyabayashi, K., Komatsu, T., Owaki, A., Baba, T., Shima, Y., Kidokoro, T., Kanai, Y., Schedl, A., Wilhelm, D., Koopman, P., Okuno, Y., & Morohashi, K.-i. (2012). Cbx2, a Polycomb Group Gene, Is Required for Sry Gene Expression in Mice. Endocrinology, 153(2), 913-924. DOI:10.1210/en.2011-1055
  67. Kenngott, R. A.-M., Vermehren, M., Ebach, K., & Sinowatz, F. (2013). The Role of Ovarian Surface Epithelium in Folliculogenesis during Fetal Development of the Bovine Ovary: A Histological and Immunohistochemical Study. Sexual Development, 7(4), 180-195. DOI:10.1159/000348881
  68. Kızılay, F., & Altay, B. (2019a). Spermatogenez, spermiyogenezis ve klinik yansımaları. Androloji Bülteni, 21(4), 177-184. DOI:10.24898/tandro.2019.27443
  69. Kızılay, F., & Altay, B. (2019b). Spermatogenez, spermiyogenezis ve klinik yansımaları.
  70. Knobil, E. (2006). Knobil and Neill's physiology of reproduction (Vol. 2). Gulf Professional Publishing.
  71. Kostereva, N., & Hofmann, M. C. (2008). Regulation of the spermatogonial stem cell niche. Reproduction in Domestic Animals, 43, 386-392. DOI:10.1111/j.1439-0531.2008.01189.x
  72. Koubova, J., Menke, D. B., Zhou, Q., Capel, B., Griswold, M. D., & Page, D. C. (2006). Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proceedings of the National Academy of Sciences, 103(8), 2474-2479. DOI:10.1073/pnas.0510813103.
  73. Krapf, D., Ruan, Y. C., Wertheimer, E. V., Battistone, M. A., Pawlak, J. B., Sanjay, A., Pilder, S. H., Cuasnicu, P., Breton, S., & Visconti, P. E. (2012). cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit. Developmental biology, 369(1), 43-53. DOI:10.1016/j.ydbio.2012.06.017.
  74. Krinke, G. (2000). The Laboratory Rat. Academic Press, 1st Ed, 150-152, 311-312.
  75. Kurimoto, K., Yabuta, Y., Ohinata, Y., Shigeta, M., Yamanaka, K., & Saitou, M. (2008). Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes & development, 22(12), 1617-1635. http://doi.org/10.1101/gad.1649908.
  76. Kusaka, M., Katoh-Fukui, Y., Ogawa, H., Miyabayashi, K., Baba, T., Shima, Y., Sugiyama, N., Sugimoto, Y., Okuno, Y., Kodama, R., Iizuka-Kogo, A., Senda, T., Sasaoka, T., Kitamura, K., Aizawa, S., & Morohashi, K.-i. (2010). Abnormal Epithelial Cell Polarity and Ectopic Epidermal Growth Factor Receptor (EGFR) Expression Induced in Emx2 KO Embryonic Gonads. Endocrinology, 151(12), 5893-5904. DOI:10.1210/en.2010-0915.
  77. Li, N., Wang, T., & Han, D. (2012). Structural, cellular and molecular aspects of immune privilege in the testis. Frontiers in immunology, 3, 152. DOI:10.3389/fimmu.2012.00152.
  78. Liu, C., Rodriguez, K., & Yao, H. H.-C. (2016). Mapping lineage progression of somatic progenitor cells in the mouse fetal testis. Development, 143(20), 3700-3710. Doi: 10.1242/dev.135756. DOI: 10.1242/dev.135756.
  79. Mazaud, S., Oreal, E., Guigon, C., Carre-Eusebe, D., & Magre, S. (2002). Lhx9 expression during gonadal morphogenesis as related to the state of cell differentiation. Gene Expression Patterns, 2(3-4), 373-377. DOI: 10.1016/S1567-133X(02)00050-9.
  80. McCabe, M. J., Allan, C. M., Foo, C. F., Nicholls, P. K., McTavish, K. J., & Stanton, P. G. (2012). Androgen initiates Sertoli cell tight junction formation in the hypogonadal (hpg) mouse. Biology of reproduction, 87(2), 38, 31-38. DOI: 10.1095/biolreprod.111.094318.
  81. McLaren, A. (1999). Signaling for germ cells. Genes Development, 13, 373-376.
  82. Meng, X., Pata, I., Pedrono, E., Popsueva, A., de Rooij, D. G., Jänne, M., Rauvala, H., & Sariola, H. (2001). Transient disruption of spermatogenesis by deregulated expression of neurturin in testis. Molecular and cellular endocrinology, 184(1-2), 33-39. DOI: 10.1016/S0303-7207(01)00649-9.
  83. Mıchela Schultz, F., & Wılson, J. D. (1974). Virilization of the Wolffian duct in the rat fetus by various androgens. Endocrinology, 94(4), 979-986.
  84. Midzak, A. S., Chen, H., Papadopoulos, V., & Zirkin, B. R. (2009). Leydig cell aging and the mechanisms of reduced testosterone synthesis. Molecular and cellular endocrinology, 299(1), 23-31. DOI: 10.1016/j.mce.2008.07.016.
  85. Migliaccio, A., Castoria, G., Domenico, M. D., de Falco, A., Bilancio, A., Lombardi, M., Barone, M. V., Ametrano, D., Zannini, M. S., & Abbondanza, C. (2000). Steroid‐induced androgen receptor–oestradiol receptor β–Src complex triggers prostate cancer cell proliferation. The EMBO journal, 19(20), 5406-5417. DOI:10.1093/emboj/19.20.5406.
  86. Miller, W. L. (2008). Steroidogenic enzymes. In Disorders of the human Adrenal cortex (Vol. 13, pp. 1-18). Karger Publishers.
  87. Miura, K., Tomita, A., & Kanai, Y. (2018). Sex Determination and Differentiation in Mammals. In Reproductive and Developmental Strategies (pp. 407-433). Springer. DOI:10.1007/978-4-431-56609-0_20
  88. Mork, L., Maatouk, D. M., McMahon, J. A., Guo, J. J., Zhang, P., McMahon, A. P., & Capel, B. (2012). Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biology of reproduction, 86(2), 37, 31-39. DOI:10.1095/biolreprod.111.095208.
  89. Morohashi, K., Baba, T., & Tanaka, M. (2013). Steroid hormones and the development of reproductive organs. Sexual Development, 7(1-3), 61-79.
  90. Mruk, D. D., & Cheng, C. (2010). Tight junctions in the testis: new perspectives. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1546), 1621-1635. DOI:10.1098/rstb.2010.0010.
  91. Mruk, D. D., & Cheng, C. Y. (2004). Sertoli-Sertoli and Sertoli-Germ Cell Interactions and Their Significance in Germ Cell Movement in the Seminiferous Epithelium during Spermatogenesis. Endocrine Reviews, 25(5), 747-806. DOI:10.1210/er.2003-0022.
  92. Mruk, D. D., & Cheng, C. Y. (2015). The mammalian blood-testis barrier: its biology and regulation. Endocrine reviews, 36(5), 564-591.
  93. Murta, D., Batista, M., Silva, E., Trindade, A., Henrique, D., Duarte, A., & Lopes‐da‐Costa, L. (2016). Notch signaling in the epididymal epithelium regulates sperm motility and is transferred at a distance within epididymosomes. Andrology, 4(2), 314-327. DOI:10.1111/andr.12144.
  94. Münsterberg, A., & Lovell-Badge, R. (1991). Expression of the mouse anti-Müllerian hormone gene suggests a role in both male and female sexual differentiation. Development, 113(2), 613-624. DOI:10.1242/dev.113.2.613.
  95. Nagamatsu, G., Kosaka, T., Kawasumi, M., Kinoshita, T., Takubo, K., Akiyama, H., Sudo, T., Kobayashi, T., Oya, M., & Suda, T. (2011). A germ cell-specific gene, Prmt5, works in somatic cell reprogramming. Journal of Biological Chemistry, 286(12), 10641-10648. DOI 10.1074/jbc.M110.216390.
  96. Nakaki, F., & Saitou, M. (2014). PRDM14: a unique regulator for pluripotency and epigenetic reprogramming. Trends in biochemical sciences, 39(6), 289-298.
  97. Nakata, H., Wakayama, T., Sonomura, T., Honma, S., Hatta, T., & Iseki, S. (2015). Three‐dimensional structure of seminiferous tubules in the adult mouse. Journal of anatomy, 227(5), 686-694. DOI:10.1111/joa.12375.
  98. Nef, S., Stévant, I., & Greenfield, A. (2019a). Chapter Six - Characterizing the bipotential mammalian gonad. In B. Capel (Ed.), Current Topics in Developmental Biology (Vol. 134, pp. 167-194). Academic Press. DOI:10.1016/bs.ctdb.2019.01.002.
  99. Nef, S., Stévant, I., & Greenfield, A. (2019b). Characterizing the bipotential mammalian gonad. Current topics in developmental biology, 134, 167-194. DOI:10.1016/bs.ctdb.2019.01.002.
  100. Neumann, F. v., von Berswordt-Wallrabe, R., Elger, W., Steinbeck, H., Hahn, J., & Kramer, M. (1970). Aspects of androgen-dependent events as studied by antiandrogens. Proceedings of the 1969 Laurentian Hormone Conference, DOI:10.1016/B978-0-12-571126-5.50013-3.
  101. Nicol, B., & Yao, H. H.-C. (2015). Gonadal identity in the absence of pro-testis factor SOX9 and pro-ovary factor beta-catenin in mice. Biology of reproduction, 93(2), 35, 31-12. DOI:10.1095/biolreprod.115.131276.
  102. Ogawa, T., Dobrinski, I., Avarbock, M. R., & Brinster, R. L. (2000). Transplantation of male germ line stem cells restores fertility in infertile mice. Nature medicine, 6(1), 29-34.
  103. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., & Saitou, M. (2009). A signaling principle for the specification of the germ cell lineage in mice. Cell, 137(3), 571-584. DOI 10.1016/j.cell.2009.03.014.
  104. Ohinata, Y., Payer, B., O'Carroll, D., Ancelin, K., Ono, Y., Sano, M., Barton, S. C., Obukhanych, T., Nussenzweig, M., & Tarakhovsky, A. (2005). Blimp1 is a critical determinant of the germ cell lineage in mice. Nature, 436(7048), 207-213. DOI:10.1038/nature03813.
  105. Ota, T., Asahina, H., Park, S.-H., Huang, Q., Minegishi, T., Auersperg, N., & Leung, P. C. (2008). HOX cofactors expression and regulation in the human ovary. Reproductive Biology and Endocrinology, 6(1), 1-9. DOI:10.1186/1477-7827-6-49.
  106. Ounjai, P., Kim, K. D., Lishko, P. V., & Downing, K. H. (2012). Three-dimensional structure of the bovine sperm connecting piece revealed by electron cryotomography. Biol Reprod, 87(3), 73. DOI:10.1095/biolreprod.112.101980.
  107. Park, S. Y., & Jameson, J. L. (2005). Minireview: Transcriptional Regulation of Gonadal Development and Differentiation. Endocrinology, 146(3), 1035-1042. DOI:10.1210/en.2004-1454.
  108. Parma, P., & Radi, O. (2012). Molecular mechanisms of sexual development. Sexual Development, 6(1-3), 7-17. DOI:10.1159/000332209.
  109. Payne, A. H. (2007). Steroidogenic enzymes in Leydig cells. In The Leydig cell in health and disease (pp. 157-171). Springer. DOI:10.1007/978-1-59745-453-7_10.
  110. Piprek, R. P., Kloc, M., & Kubiak, J. Z. (2016). Early development of the gonads: origin and differentiation of the somatic cells of the genital ridges. In Molecular Mechanisms of Cell Differentiation in Gonad Development (pp. 1-22). Springer. DOI:10.1007/978-3-319-31973-5_1.
  111. Pitetti, J.-L., Calvel, P., Romero, Y., Conne, B., Truong, V., Papaioannou, M. D., Schaad, O., Docquier, M., Herrera, P. L., & Wilhelm, D. (2013). Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice. PLoS Genet, 9(1), e1003160. DOI:10.1371/journal.pgen.1003160.
  112. Plant, T. M., & Zeleznik, A. J. (2014). Knobil and Neill's physiology of reproduction. Academic Press. Pointis, G., & Segretain, D. (2005). Role of connexin-based gap junction channels in testis. Trends in Endocrinology & Metabolism, 16(7), 300-306.
  113. Potter, S. J., & DeFalco, T. (2017). Role of the testis interstitial compartment in spermatogonial stem cell function. Reproduction (Cambridge, England), 153(4), R151. doi: 10.1530/REP-16-0588.
  114. Pugazhenthi, S., Nesterova, A., Sable, C., Heidenreich, K. A., Boxer, L. M., Heasley, L. E., & Reusch, J. E.-B. (2000). Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. Journal of Biological Chemistry, 275(15), 10761-10766.
  115. Rastrelli, G., Corona, G., Mannucci, E., & Maggi, M. (2014). Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study. Andrology, 2(6), 794-808. DOI:10.1111/andr.262.
  116. Rejraji, H., Sion, B., Prensier, G., Carreras, M., Motta, C., Frenoux, J.-M., Vericel, E., Grizard, G., Vernet, P., & Drevet, J. R. (2006). Lipid remodeling of murine epididymosomes and spermatozoa during epididymal maturation. Biology of reproduction, 74(6), 1104-1113. DOI:10.1095/biolreprod.105.049304.
  117. Rey, R., Josso, N., & Racine, C. (2020). Sexual differentiation. Endotext [Internet].
  118. Roberts, K. P., & Chauvin, T. R. (2019). Molecular mechanisms of testosterone action on the testis. Current Opinion in Endocrine and Metabolic Research, 6, 29-33. DOI:10.1016/j.coemr.2019.03.003.
  119. Roth, M. Y., Lin, K., Amory, J., Matsumoto, A., Anawalt, B., Snyder, C., Kalhorn, T., Bremner, W., & Page, S. (2010). Serum LH correlates highly with intratesticular steroid levels in normal men. Journal of andrology, 31(2), 138-145. DOI:10.2164/jandrol.109.008391.
  120. Russell, L. D., Ettlin, R. A., Hikim, A. P. S., & Clegg, E. D. (1993). Histological and Histopathological Evaluation of the Testis. International Journal of Andrology, 16(1), 83-83. DOI:10.1111/j.1365-2605.1993.tb01156.x.
  121. Ryu, B.-Y., Kubota, H., Avarbock, M. R., & Brinster, R. L. (2005). Conservation of spermatogonial stem cell self-renewal signaling between mouse and rat. Proceedings of the National Academy of Sciences, 102(40), 14302-14307.
  122. Santi, D., Potì, F., Simoni, M., & Casarini, L. (2018). Pharmacogenetics of G-protein-coupled receptors variants: FSH receptor and infertility treatment. Best Practice & Research Clinical Endocrinology & Metabolism, 32(2), 189-200. DOI:10.1016/j.beem.2018.01.001.
  123. Sarma, K., & Devi, J. (2012). Changes in the seminiferous epithelium of the testes during postnatal development in Assam goat. Anatomy research international, 2012. DOI:10.1155/2012/620924
  124. Schäfer, S., Anschlag, J., Nettersheim, D., Haas, N., Pawig, L., & Schorle, H. (2011). The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours. International journal of andrology, 34(4pt2), e152-e159. DOI:10.1111/j.1365-2605.2011.01167.x
  125. Schmahl, J., Eicher, E. M., Washburn, L. L., & Capel, B. (2000). Sry induces cell proliferation in the mouse gonad. Development, 127(1), 65-73. DOI:10.1242/dev.127.1.65
  126. Schnabel, C. A., Selleri, L., & Cleary, M. L. (2003). Pbx1 is essential for adrenal development and urogenital differentiation. Genesis, 37(3), 123-130. DOI:10.1002/gene.10235. Scobey, M. J., Bertera, S., Somers, J. P., Watkins, S. C., Zeleznik, A. J., & Walker, W. H. (2001). Delivery of a cyclic adenosine 3′, 5′-monophosphate response element-binding protein (creb) mutant to seminiferous tubules results in impaired spermatogenesis. Endocrinology, 142(2), 948-954. DOI:10.1210/endo.142.2.7948
  127. Seda O, L. F., Sedova L (2006). Sex Determination. Genetics and Genomics, Multimedia E-textbook of Medical Biology.
  128. Sekido, R., & Lovell-Badge, R. (2008). Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature, 453(7197), 930-934. DOI:10.1038/nature06944
  129. Shang, Y., Myers, M., & Brown, M. (2002). Formation of the androgen receptor transcription complex. Molecular cell, 9(3), 601-610. DOI:10.1016/S1097-2765(03)00237-5
  130. Sharma, R., Bhat, R., Goyal, A., & Bhardwaj, J. (2015). Germ cells apoptosis during spermatogenesis in mammals. Journal of Entomology and Zoology Studies, 3(3), 506-515.
  131. Sharpe, R. M. (2012). Sperm counts and fertility in men: a rocky road ahead: Science & Society Series on Sex and Science. EMBO reports, 13(5), 398-403. DOI:10.1038/embor.2012.50
  132. Shetty, G., & Meistrich, M. L. (2007). The missing niche for spermatogonial stem cells: do blood vessels point the way? Cell Stem Cell, 1(4), 361-363. DOI 10.1016/j.stem.2007.09.013
  133. Smitz, J., & Cortvrindt, R. G. (2002). The earliest stages of folliculogenesis in vitro. Reproduction, 123(2), 185-202. DOI:10.1530/rep.0.1230185
  134. Starz-Gaiano, M., & Lehmann, R. (2001). Moving towards the next generation. Mechanisms of development, 105(1-2), 5-18. DOI:10.1016/S0925-4773(01)00392-6
  135. Stévant, I., Kühne, F., Greenfield, A., Chaboissier, M.-C., Dermitzakis, E. T., & Nef, S. (2018). Single-cell transcriptomics of the mouse gonadal soma reveals the establishment of sexual dimorphism in distinct cell lineages. BioRxiv, 410407. DOI:10.1101/410407
  136. Sullivan, R., & Saez, F. (2013). Epididymosomes, prostasomes, and liposomes: their roles in mammalian male reproductive physiology. Reproduction, 146(1), R21-R35. DOI:10.1530/REP-13-0058
  137. Tadokoro, Y., Yomogida, K., Ohta, H., Tohda, A., & Nishimune, Y. (2002). Homeostatic regulation of germinal stem cell proliferation by the GDNF/FSH pathway. Mechanisms of development, 113(1), 29-39. DOI:10.1016/S0925-4773(02)00004-7
  138. Taylor, R. M. (2020). Investigation into germ cell fate determination of rat embryonic stem cells. http://dx.doi.org/10.7488/era/281
  139. Tsai, M.-Y., Yeh, S.-D., Wang, R.-S., Yeh, S., Zhang, C., Lin, H.-Y., Tzeng, C.-R., & Chang, C. (2006). Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. Proceedings of the National Academy of Sciences, 103(50), 18975-18980. DOI:10.1073/pnas.0608565103
  140. Von Ledebur, E., Almeida, J., Loss, E., & Wassermann, G. (2002). Rapid effect of testosterone on rat Sertoli cell membrane potential. Relationship with K+ ATP channels. Hormone and metabolic research, 34(10), 550-555. DOI: 10.1055/s-2002-35426
  141. Walker, W. H. (2011). Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis, 1(2), 116-120. DOI:10.4161/spmg.1.2.16956
  142. Wang, Q., Lan, Y., Cho, E.-S., Maltby, K. M., & Jiang, R. (2005). Odd-skipped related 1 (Odd1) is an essential regulator of heart and urogenital development. Developmental biology, 288(2), 582-594. DOI:10.1016/j.ydbio.2005.09.024
  143. Wang, R.-S., Yeh, S., Tzeng, C.-R., & Chang, C. (2009). Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice. Endocrine reviews, 30(2), 119-132.
  144. Wear, H. M., Eriksson, A., Yao, H. H.-C., & Watanabe, K. H. (2017). Cell-based computational model of early ovarian development in mice. Biology of reproduction, 97(3), 365-377. DOI:10.1093/biolre/iox089
  145. Weinbauer, G. F., & Nieschlag, E. (1998). The role of testosterone in spermatogenesis. In Testosterone: action-deficiency-substitution (pp. 143-168). Springer. DOI:10.1007/978-3-642-72185-4_4
  146. Welling, M., & Geijsen, N. (2013). Uncovering the true identity of naive pluripotent stem cells. Trends in cell biology, 23(9), 442-448.
  147. Woolley, D. (2003). Motility of spermatozoa at surfaces. REPRODUCTION-CAMBRIDGE-, 126(2), 259-270. DOI:10.1530/rep.0.1260259
  148. Xia, W., & Cheng, C. Y. (2005). TGF-β3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras/ERK signaling pathway: an in vivo study. Developmental biology, 280(2), 321-343. DOI:10.1016/j.ydbio.2004.12.036
  149. Yamatoya, K., ITO, C., ARAKI, M., FURUSE, R., & TOSHIMORI, K. (2011). Dynamics of the mammalian sperm head: modifications and maturation events from spermatogenesis to egg activation Dynamics of the mammalian sperm head: modifications and maturation events from spermatogenesis to egg activation, 2009. Reproductive medicine and biology, 10(2), 97-103.
  150. Yamazaki, Y., Mann, M. R. W., Lee, S. S., Marh, J., McCarrey, J. R., Yanagimachi, R., & Bartolomei, M. S. (2003). Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proceedings of the National Academy of Sciences, 100(21), 12207-12212. DOI:10.1073/pnas.2035119100
  151. Yoshida, S., Sukeno, M., Nakagawa, T., Ohbo, K., Nagamatsu, G., Suda, T., & Nabeshima, Y.-i. (2006). The first round of mouse spermatogenesis is a distinctive program that lacks the self-renewing spermatogonia stage. Development, 133(8), 1495-1505. DOI:10.1242/dev.02316
  152. Young, L. E. (2006). Focus on stem cells in reproduction. Reproduction, 132(5), 671-672. DOI:10.1530/REP-06-0191 Zheng, Y., Zhang, Y., Qu, R., He, Y., Tian, X., & Zeng, W. (2014). Spermatogonial stem cells from domestic animals: progress and prospects. Reproduction, 147(3), R65-R74. DOI: 10.1530/REP-13-0466
  153. Zhou, Q., Nie, R., Prins, G. S., Saunders, P. T., Katzenellenbogen, B. S., & Hess, R. A. (2002). Localization of androgen and estrogen receptors in adult male mouse reproductive tract. Journal of andrology, 23(6), 870-881. DOI:10.1002/j.1939-4640.2002.tb02345.x
  154. Zhou, W., De Iuliis, G. N., Dun, M. D., & Nixon, B. (2018). Characteristics of the epididymal luminal environment responsible for sperm maturation and storage. Frontiers in endocrinology, 9, 59. DOI: 10.3389/fendo.2018.00059
  155. Krapf, D., Ruan, Y. C., Wertheimer, E. V., Battistone, M. A., Pawlak, J. B., Sanjay, A., Pilder, S. H., Cuasnicu, P., Breton, S., & Visconti, P. E. (2012). cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit. Developmental biology, 369(1), 43-53. DOI:10.1016/j.ydbio.2012.06.017.
  156. Mork, L., Maatouk, D. M., McMahon, J. A., Guo, J. J., Zhang, P., McMahon, A. P., & Capel, B. (2012). Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biology of reproduction, 86(2), 37, 31-39. DOI:10.1095/biolreprod.111.095208.
  157. Mruk, D. D., & Cheng, C. (2010). Tight junctions in the testis: new perspectives. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1546), 1621-1635. DOI:10.1098/rstb.2010.0010.
  158. Mruk, D. D., & Cheng, C. Y. (2004). Sertoli-Sertoli and Sertoli-Germ Cell Interactions and Their Significance in Germ Cell Movement in the Seminiferous Epithelium during Spermatogenesis. Endocrine Reviews, 25(5), 747-806. DOI:10.1210/er.2003-0022.
  159. Nef, S., Stévant, I., & Greenfield, A. (2019a). Chapter Six - Characterizing the bipotential mammalian gonad. In B. Capel (Ed.), Current Topics in Developmental Biology (Vol. 134, pp. 167-194). Academic Press. DOI:10.1016/bs.ctdb.2019.01.002.
  160. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., & Saitou, M. (2009). A signaling principle for the specification of the germ cell lineage in mice. Cell, 137(3), 571-584. DOI 10.1016/j.cell.2009.03.014.
  161. Park, S. Y., & Jameson, J. L. (2005). Minireview: Transcriptional Regulation of Gonadal Development and Differentiation. Endocrinology, 146(3), 1035-1042. DOI:10.1210/en.2004-1454.
  162. Rastrelli, G., Corona, G., Mannucci, E., & Maggi, M. (2014). Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study. Andrology, 2(6), 794-808. DOI:10.1111/andr.262.
  163. Russell, L. D., Ettlin, R. A., Hikim, A. P. S., & Clegg, E. D. (1993). Histological and Histopathological Evaluation of the Testis. International Journal of Andrology, 16(1), 83-83. DOI:10.1111/j.1365-2605.1993.tb01156.x.