{"paper_id":"28d9cfd3-8f04-4bfa-8166-8880ac8517fa","body_text":"EDITORIAL\nCell biology solves mysteries of reproduction\nPeter Sutovsky\nPublished online: 4 August 2012\n# Springer-V erlag 2012\nAbstract Reproduction and fertility have been objects of\nkeen inquiry since the dawn of humanity. Medieval anato-\nmists provided the first accurate depictions of the female\nreproductive system, and early microscopists were fascinat-\ned by the magnified sight of sperm cells. Initial successes\nwere achieved in the in vitro fertilization of frogs and the\nartificial insemination of dogs. Gamete and embryo research\nwas in the cradle of modern cell biology, providing the first\nevidence of the multi-cellular composition of living beings\nand pointing out the importance of chromosomes for hered-\nity. In the 20th century, reproductive research paved the way\nfor the study of the cytoskeleton, cell signaling, and the cell\ncycle. In the last three decades, the advent of reproductive\ncell biology has brought us human in vitro fertilization,\nanimal cloning, and human and animal embryonic stem\ncells. It has contributed to the development of transgenesis,\nproteomics, genomics, and epigenetics. This Special Issue\nrepresents a sample of the various areas of reproductive\nbiology, with emphasis on molecular and cell biological\naspects. Advances in spermatology, ovarian function, fertil-\nization, and maternal-fetal interactions are discussed within\nthe framework of fertility and diseases such as endometri-\nosis and diabetes.\nPaleolithic fertility symbols such as the V enus of Willendorf,\ndating back to 24,000 –22,000 BC, indicate the great interest\nshown in reproduction and fertility even during the early days\nof humanity. Tales of early artificial insemination, e.g., thieves\ninseminating mares with sponges soaked with semen stolen\nfrom their rivals’ valuable stallions, have been passed down in\nMiddle Eastern folklore (Foote 2002 ). The original\nRenaissance man, Leonardo Da Vinci, was a keen anatomist,\nleaving us detailed illustrations of dissections of female repro-\nductive system, including a depiction of a pregnant human\nuterus with a fetus. In the 18th century, Lazzaro (Abé)\nSpallanzani, a Catholic priest with a knack for researching\nreproduction, fashioned tiny tubes to collect the semen of\nmale frogs and established that physical contact between the\nsperm and egg is necessary for embryo development.\nSpallanzani used a scientific method with multiple replicates\nof these arguably first ever in vitro fertilization experiments; in\n1784, he performed the first successful documented artificial\ninsemination in dogs (Pinto-Correia 1997).\nGametes are among the largest and most peculiar cells in\nthe human or animal body, making them an ideal model\nsystem for studying a variety of cellular structures, path-\nways, and mechanisms. Not surprisingly, gametes were\namong the earliest cells to which the scientific method and\ntools were applied. Among the first cells ever observed\nunder a microscope by van Leeuwenhoek and his disciple\nHamm were human sperm cells. The modern hypothesis of\ncellular composition of multicellular bodies was introduced\nin 1839 by Schwann and Schleiden based in part on the\nobservation that a complete organism develops from a single\ncell, namely the fertilized ovum (Aszmann 2000). In the late\n19th and early 20th centuries, Theodor Boveri used sea\nurchin eggs and embryos to formulate the chromosome\ntheory of inheritance (Boveri-Sutton theory). Boveri ’s work\non the centrosome in sea urchin zygotes set the stage for the\nstudy of the cytoskeleton, a prominent area of today ’s field\nof cell biology (Baltzer 1964). The use of invertebrate and\nlower vertebrate gametes brought about many more advan-\nces in the modern era of cell biology. For example, the\nobservations of calcium release in fertilized medaka eggs\n(Gilkey et al. 1978 ) ushered in cell signaling/signal\nP . Sutovsky (*)\nAnimal Sciences, University of Missouri-Columbia,\nS141 ASRC, 920 East Campus Drive,\nColumbia MO 65211-5300, USA\ne-mail: SutovskyP@missouri.edu\nCell Tissue Res (2012) 349:631 –633\nDOI 10.1007/s00441-012-1480-y\n\ntransduction studies. Xenopus oocytes and their cytosolic\nextracts have been the materials of choice for the study of\nthe cell cycle, tracing back to the ingenious experiments of\nYoshio Masui (Masui and Markert 1971).\nThe cell biological approach to the study of reproduction\nhas made possible important advances in medicine. The\npioneering work of Edwards and Steptoe, which to date\nhas resulted in the births of a million babies by assisted\nfertilization, was recently honored by the Nobel Prize. In the\nlast two decades, reproductive biology has built on the\nresearch leading to this breakthrough and has given us\nhuman embryonic stem cells, making regenerative medicine\na reality (Gearhart and Coutifaris 2011). Work on somatic\ncell nuclear transfer not only yielded the first cloned mam-\nmal, but also gave us information about genome reprogram-\nming, leading to the development of induced pluripotent\nstem cells (Ezashi et al. 2012) and animal models of human\ndisease (Zhao et al. 2010). Advances are being made toward\nthe production of male and female gametes outside of the\ngonads, for transgenesis and the restoration of fertility in\ncancer and infertility patients (Dores et al. 2012). Gametes\nand embryos are also useful in the hot new areas of cell\nbiology such as the study of small non-coding RNAs and\nepigenetics (Hossain et al. 2012). Inversely, basic develop-\nmental mechanisms such as the uniparental inheritance of\nmitochondrial DNA, an aspect that is important for evolution-\nary biology, are being explored primarily in zygotes and\npreimplantation embryos, as reviewed by St John ( 2012).\nThe suspected link between infertility, cellular metabolism,\nand obesity is now being investigated by modern cell biolog-\nical approaches by using mammalian embryos (Schoeller et al.\n2012). Cellular signaling between mother and embryo/fetus\n(Geisert et al. 2012) and the embryonic origin of adult-onset\ndisease are now better understood (Gallo et al. 2012), thereby\nbenefitting the treatment of serious reproductive disorders\nsuch as endometriosis (Stilley et al.2012). Further insight into\nfemale fertility can be gained from an improved understanding\nof folliculogenesis and ovarian function (Pohler et al. 2012;\nMcFee et al. 2012).\nLight and electron microscopy combined with organelle\nfractionation, proteomics, and molecular biology have pro-\nvided a deeper understanding of sperm accessory structures,\nsuch as the sperm acrosome and perinuclear theca (see\nregular article by Ferrer et al. 2012a and review by Ferrer\net al. 2012b). As reviewed by Belleannée et al. ( 2012),\ngenomic and proteomic studies provide new insight into\nprocess of epididymal sperm maturation.These advances\nthen allow the exploration of sperm function during fertil-\nization (Ferrer et al. 2012b) and the relationship of the sperm\nproteome with male fertility (Govindaraju et al. 2012).\nWithin the area of fertilization research, important advances\nhave been made in the study of sperm-egg coat interactions\nincluding the structure and identity of sperm receptor\nproteins on the egg coat surface (Gupta et al. 2012) and\nthe signaling pathways involved in sperm capacitation, a\ncascade of events that prepare the sperm cells within the\nfemale oviduct for fertilization (Signorelli et al. 2012).\nThese events are mediated by ion channels that are present\nwithin the sperm plasma membrane and that are responsible\nfor communication between the sperm cell interior and the\nmilieu of the female reproductive system (Darszon et al.\n2012). In addition to mammalian models, spermatogenesis\nis being researched in invertebrate and lower vertebrate\nsystems (McClusky 2012).\nThe present Special Issue on Reproduction thus offers a\nsample of the various areas of reproductive biology, with an\nobvious emphasis on its molecular and cell biological aspects.\nReferences\nAszmann OC (2000) The life and work of Theodore Schwann. J\nReconstr Microsurg 16:291 –295\nBaltzer F (1964) Theodor Boveri. Science 144:809 –815\nBelleannée C, Thimon V , Sullivan R (2012) Region-specific gene\nexpression in the epididymis. Cell Tissue Res. doi: 10.1007/\ns00441-012-1381-0\nDarszon A, Sánchez-Cárdenas C, Orta G, Sánchez-Tusie AA, Beltrán\nC, López-González I, Granados-González G, Treviño CL (2012)\nAre TRP channels involved in sperm development and function?\nCell Tissue Res. doi: 10.1007/s00441-012-1397-5\nDores C, Alpaugh W, Dobrinski I (2012) From in vitro culture to in\nvivo models to study testis development and spermatogenesis.\nCell Tissue Res. doi: 10.1007/s00441-012-1457-x\nEzashi T, Telugu BPVL, Roberts RM (2012) Model systems for\nstudying trophoblast differentiation from human pluripotent stem\ncells. Cell Tissue Res. doi: 10.1007/s00441-012-1371-2\nFerrer M, Rodriguez H, Zara L, Y u Y , Xu W, Oko R (2012a) MMP2\nand acrosin are major proteinases associated with the inner acro-\nsomal membrane and may cooperate in sperm penetration of the\nzona pellucida during fertilization. Cell Tissue Res. doi: 10.1007/\ns00441-012-1429-1\nFerrer M, Xu W, Oko R (2012b) The composition, protein genesis and\nsignificance of the inner acrosomal membrane of eutherian sperm.\nCell Tissue Res. doi: 10.1007/s00441-012-1433-5\nFoote RH (2002) The history of artificial insemination: selected notes\nand notables. J Anim Sci 80:1 –10\nGallo LA, Tran M, Master JS, Moritz KM, Wlodek ME (2012) Mater-\nnal adaptations and inheritance in the transgenerational program-\nming of adult disease. Cell Tissue Res. doi: 10.1007/s00441-012-\n1411-y\nGearhart J, Coutifaris C (2011) In vitro fertilization, the Nobel Prize,\nand human embryonic stem cells. Cell Stem Cell 8:12 –15\nGeisert R, Fazleabas A, Lucy M, Mathew D (2012) Interaction of the\nconceptus and endometrium to establish pregnancy in mammals: role\nof interleukin 1β. Cell Tissue Res. doi:10.1007/s00441-012-1356-1\nGilkey JC, Jaffe LF, Ridgway EB, Reynolds GT (1978) A free calcium\nwave traverses the activating egg of the medaka, Oryzias latipes.J\nCell Biol 76:448 –466\nGovindaraju A, Dogan S, Rodriguez-Osorio N, Grant K, Kaya A,\nMemili E (2012) Delivering value from sperm proteomics for\nfertility. Cell Tissue Res. doi: 10.1007/s00441-012-1452-2\nGupta SK, Bhandari B, Shrestha A, Biswal BK, Palaniappan C, Malhotra\nSS, Gupta N (2012) Mammalian zona pellucida glycoproteins:\n632 Cell Tissue Res (2012) 349:631 –633\n\nstructure and function during fertilization. Cell Tissue Res.\ndoi:10.1007/s00441-011-1319-y\nHossain MM, Sohel MMH, Schellander K, Tesfaye D (2012)\nCharacterization and importance of microRNAs in mammalian\ngonadal functions. Cell Tissue Res. doi: 10.1007/s00441-012-\n1469-6\nMasui Y , Markert CL (1971) Cytoplasmic control of nuclear behavior\nduring meiotic maturation of frog oocytes. J Exp Zool 177:129–145\nMcClusky LM (2012) Coordination of spermatogenic processes in the\ntestis: lessons from cystic spe rmatogenesis. Cell Tissue Res.\ndoi:10.1007/s00441-011-1288-1\nMcFee RM, Rozell TG, Cupp AS (2012) The balance of proangiogenic\nand antiangiogenic VEGFA isoforms regulate follicle develop-\nment. Cell Tissue Res. doi: 10.1007/s00441-012-1330-y\nPinto-Correia C (1997) The Ovary of Eve. University of Chicago\nPress, Chicago London\nPohler KG, Geary TW, Atkins JA, Perry GA, Jinks EM, Smith\nMF (2012) Follicular determinants of pregnancy establishment\nand maintenance. Cell Tissue Res. doi: 10.1007/s00441-012-\n1386-8\nSchoeller EL, Schon S, Moley K H (2012) The effects of type 1\ndiabetes on the hypothalamic, pituitary and testes axis. Cell Tissue\nRes. doi: 10.1007/s00441-012-1387-7\nSignorelli J, Diaz ES, Morales P (2012) Kinases, phosphatases and\nproteases during sperm capacitation. Cell Tissue Res. doi:10.1007/\ns00441-012-1370-3\nSt John JC (2012) Transmission, i nheritance and replication of\nmitochondrial DNA in mammals: implications for reproductive\nprocesses and infertility. Cell Tissue Res. doi: 10.1007/s00441-\n012-1444-2\nStilley JAW, Birt JA, Sharpe-Timms KL (2012) Cellular and molecular\nbasis for endometriosis-associated infertility. Cell Tissue Res.\ndoi:10.1007/s00441-011-1309-0\nZhao J, Whyte J, Prather RS (2010) Effect of epigenetic regulation\nduring swine embryogenesis and on cloning by nuclear transfer.\nCell Tissue Res 341:13 –21\nCell Tissue Res (2012) 349:631 –633 633","source_license":"public-domain-us","license_restricted":false}