Spermatogenesis最新文献

Fatty acids are precursors of potent lipid signaling molecules. They are stored in membrane phospholipids and released by phospholipase A₂ (PLA₂). Lysophospholipid acyltransferases (ATs) oppose PLA₂ by re-esterifying fatty acids into phospholipids, in a biochemical pathway known as the Lands Cycle. Drosophila Lands Cycle ATs oys and nes, as well as 7 predicted PLA₂ genes, are expressed in the male reproductive tract. Oys and Nes are required for spermatid individualization. Individualization, which occurs after terminal differentiation, invests each spermatid in its own plasma membrane and removes the bulk of the cytoplasmic contents. We developed a quantitative assay to measure individualization defects. We demonstrate that individualization is sensitive to temperature and age but not to diet. Mutation of the cyclooxygenase Pxt, which metabolizes fatty acids to prostaglandins, also leads to individualization defects. In contrast, modulating phospholipid levels by mutation of the phosphatidylcholine lipase Swiss cheese (Sws) or the ethanolamine kinase Easily shocked (Eas) does not perturb individualization, nor does Sws overexpression. Our results suggest that fatty acid derived signals such as prostaglandins, whose abundance is regulated by the Lands Cycle, are important regulators of spermatogenesis.

In the mammalian testis such as in rats, a unique actin-rich cell-cell adherens junction (AJ) known as ectoplasmic specialization (ES) is found in the seminiferous epithelium. ES is conspicuously found between Sertoli cells near the basement membrane known as the basal ES, which together with tight junction (TJ), gap junction, and desmosome constitute the blood-testis barrier (BTB). The BTB, in turn, anatomically divides the seminiferous epithelium into the basal and the adluminal (apical) compartment. On the other hand, ES is also found at the Sertoli-spermatid interface known as apical ES which is the only anchoring device for developing step 8-19 spermatids during spermiogenesis. One of the most typical features of the ES is the array of actin microfilament bundles that lie perpendicular to the Sertoli cell plasma membrane and are sandwiched in-between the cisternae of endoplasmic reticulum and the Sertoli cell plasma membrane. While these actin filament bundles confer the adhesive strength of Sertoli cells at the BTB and also spermatids in the adluminal compartment, they must be rapidly re-organized from their bundled to unbundled/branched configuration and vice versa to provide plasticity to the ES so that preleptotene spermatocytes and spermatids can be transported across the immunological barrier and the adluminal compartment, respectively, during the epithelial cycle of spermatogenesis. Fascin is a family of actin microfilament cross-linking and bundling proteins that is known to confer bundling of parallel actin microfilaments in mammalian cells. A recent report has illustrated the significance of a fascin protein called fascin 1 in actin microfilaments at the ES, pertinent to its role in spermatogenesis (Gungor-Ordueri et al. Am J Physiol Endocrinol Metab 307, E738-753, 2004 (DOI:10.1152/ajpendo.00113.2014). In this Commentary, we critically evaluate these findings in light of the role of fascin in other mammalian cells, providing some insightful information for future investigations.

In most bony fishes, testes are paired elongated organs that are attached to the dorsal wall of the body by a mesorchium. Histological examination of teleost testes, and also in all vertebrates, shows that the testes are formed of germ cells and somatic cells, comprising the germinal and interstitial compartments. Both compartments are separated by a basement membrane. The germ cells may be spermatogonia, meiotic spermatocytes and haploid spermatids that differentiate into spermatozoa. The process of spermatogenesis includes a sequence of morphological and physiological changes of germ cells that begin with the differentiation of spermatogonia that become meiotic spermatocytes. After the second meiotic division, through a process of spermiogenesis, these differentiate into spermatozoa. Spermatogonia associate with Sertoli cells to form spermatocysts or cysts. The cyst is the unit of spermatogenic function, composed of a cohort of isogenic germ cells surrounded by encompassing Sertoli cells. The teleost testis is organized morphologically into 3 types of testis: 1) tubular testis type, present in lower bony fishes as salmonids, cyprinids and lepisosteids; 2) unrestricted spermatogonial testis type, found in neoteleosts except Atherinomorpha; and 3) restricted spermatogonial testis type, characteristic of all Atherinomorpha. The morphology of the testicular germinal epithelium changes during the annual reproductive cycle, reflecting reproductive seasonality.

Testicular histological alterations following Sertoli cell cytoskeleton disruption are numerous. The Sertoli cell cytoskeleton is comprised of intermediate filaments, microtubules, microfilaments and their direct interacting proteins and performs essential functions including structural support of the seminiferous epithelium, apicobasal movement of elongate spermatids, and release of elongate spermatids from the seminiferous epithelium during spermiation. This review summarizes the histological changes occurring after disruption of the Sertoli cell cytoskeleton, including the signature lesion of seminiferous epithelium sloughing. By presenting examples of histological changes after exposure to toxins or toxicants directly affecting the Sertoli cell cytoskeleton or genetic manipulations of this cytoskeleton, the toxicologist observing similar histological changes associated with exposure to novel compounds can use this information to generate hypotheses about a potential mode of action.

Histological structure of the testes and development of spermatozoa in Jenynsia species is described using light, scanning and transmission electron microscopy. The testis type is restricted spermatogonial, wherein spermatogonia are restricted to the distal ends of lobules, typical of the Atherinomorpha, and spermatogenesis is continuous throughout the year in wild-caught fish. Within the testicular lobes there are lobular germinal compartments wherein the functional units are spermatocysts, whose borders are formed by Sertoli cells. Spermatocysts may contain meiotic primary spermatocytes, secondary spermatocytes, spermatids, undergoing spermiogenesis, or spermatozoa. Spermatocysts with later stages of developing sperm are located proximal to the testicular ducts. During spermiogenesis, spermatid nuclei become elongated. As this occurs, the nucleus develops a deep, central fossa that contains the centriolar complex. As the flagellum grows, enlarging spermatid mitochondria migrate posteriorly alongside the flagellum but remain separated from it by the cytoplasmatic canal, an indentation of the plasma membrane. Between the enlarged mitochondria and plasma membrane, a sub-mitochondrial net develops. In longitudinal sections, the enlarged mitochondria are stacked in a zig-zag fashion, and in transverse sections they appear as a ring surrounding the flagellum, but separated from it by the cytoplasmic canal. Spermatozoa of the 3 jenynsiid species have an introsperm complex composed of a long mid-piece whose flagellum has a single "wing." Within the efferent ducts and the tubular gonopodium, sperm are lightly packed in a side by side fashion which facilitates their transfer into the female reproductive tract. This study presents detailed descriptions of testicular organization and cytological characterization of the stages of spermatozoa differentiation in 3 species of Jenynsia from northwestern Argentina (J. alternimaculata, J. multidentata and J. maculata), in order to contribute to the understanding of testicular structure and development of spermatozoa in the context of evolution of viviparity in this fish lineage.

The testicular histology and cytology of spermatogenesis in Graptemys pseudogeographica kohnii were examined using specimens collected between July 1996 and May 2004 from counties in northeastern Arkansas. A histological examination of the testes and germ cell cytology indicates a postnuptial testicular cycle of spermatogenesis and a major fall spermiation event. The majority of the germ cell populations in May and June specimens are represented by resting spermatogonia, type A spermatogonia, type B spermatogonia, pre-leptotene spermatocytes, and numerous Sertoli cell nuclei near the basement membrane. The start of proliferation is evident as spermatogonia in metaphase are present near the basal lamina and many of these germ cells have entered meiosis in June seminiferous tubules. Major spermatogenic events occur in the June and July specimens and result in an increased height of the seminiferous epithelium and increased diameter of the seminiferous tubules. The germ cell population during this time is represented by spermatogonia (type A, B, and resting), hypertrophic cells, large populations of early primary spermatocytes, and early round spermatids. By September, the major germ cell population has progressed past meiosis with abundant round and early elongating spermatids dominating the seminiferous epithelium. October seminiferous epithelia are marked by a decreas in height and mature spermatozoa fill the luminal space. Round and elongating spermatids constitute the largest portion of the germ cell population. Following the spermiation event, the testes enter a period of quiescence that lasts till the next spermatogenic cycle, which begins in the subsequent spring. Based on the cytological development of the seminiferous tubules revealed by our study, Graptemys pseudogeographica kohnii demonstrates a temporal germ cell development strategy similar to other temperate reptiles. A single major generation of germ cells progresses through spermatogenesis each year resulting in a single spermiation event with sperm stored within the epididymis until the next spring mating season.

Oviparous species of Sceloporus exhibit either seasonal or continuous spermatogenesis and populations from high-elevation show a seasonal pattern known as spring reproductive activity. We studied the spermatogenic cycle of a high-elevation (2700 m) population of endemic oviparous lizard, Sceloporus aeneus, that resided south of México, D.F. Histological analyses were performed on the testes and reproductive ducts from individual lizards collected monthly. This population of S. aeneus showed a seasonal pattern of spermatogenesis, with 4 successive phases common in other lizards. These include: 1) Quiescence in August, which contained solely spermatogonia and Sertoli cells; 2) Testicular recrudescence (September-January) when testes became active with mitotic spermatogonia, spermatocytes beginning meiosis, and the early stages of spermiogenesis with spermatids; 3) Maximum testicular activity occurred from March to May and is when the largest spermiation events ensued within the germinal epithelia, which were also dominated by spermatids and spermiogenic cells; 4) Testicular regression in June was marked with the number of all germs cells decreasing rapidly and spermatogonia dominated the seminiferous epithelium. February was a transitional month between recrudescence and maximum activity. The highest sperm abundance in the lumina of epididymides was during maximum testicular activity (March-May). Thus, before and after these months fewer spermatozoa were detected within the excurrent ducts as the testis transitions from recrudescence to maximum activity in February and from maximum activity to quiescence in June. Maximum spermatogenic activity corresponds with warmest temperatures at this study site. This pattern known as spring reproductive activity with a fall recrudescence was similar to other oviparous species of genus Sceloporus.

Evaluation of testicular functions (production of sperm and androgens) is an important aspect of preclinical safety assessment and testicular toxicity is comparatively far more common than ovarian toxicity. This chapter focuses (1) on the histological sequelae of disturbed reproductive endocrinology in rat, dog and nonhuman primates and (2) provides a review of our current understanding of the roles of gonadotropins and androgens. The response of the rodent testis to endocrine disturbances is clearly different from that of dog and primates with different germ cell types and spermatogenic stages being affected initially and also that the end-stage spermatogenic involution is more pronounced in dog and primates compared to rodents. Luteinizing hormone (LH)/testosterone and follicle-stimulating hormone (FSH) are the pivotal endocrine factors controlling testicular functions. The relative importance of either hormone is somewhat different between rodents and primates. Generally, however, both LH/testosterone and FSH are necessary for quantitatively normal spermatogenesis, at least in non-seasonal species.

Protein phosphorylation and de-phosphorylation events are crucial in deciding the fate of cells. They regulate cellular growth, differentiation and cell death, and kinases are the key players of these events. The members of ser/thr kinases and tyrosine kinases form the majority of protein kinase family, exerting their regulatory mechanism in almost all cells. In testis, they impact signal transduction events, regulate all stages of sperm development from mitosis through fertilization. Understanding the function of these kinases at the structural level and studying their interactions with inhibitors can help in understanding the machinery of spermatogenesis. In view of this, we have reviewed some of the prominent kinases that are known to play a role in spermatogenesis. A better understanding of the impacts of kinase inhibition on spermatogenesis should aid in the interpretation of lesions and hopefully further the development of more efficient and potent drug candidates.