The making of abnormal spermatozoa: cellular and molecular mechanisms underlying pathological spermiogenesis |
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Authors: | Hector E Chemes Vanesa Y Rawe |
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Institution: | 1. Laboratory of Testicular Physiology and Pathology, Center for Research in Endocrinology (CEDIE), National Research Council (CONICET), Endocrinology Division, Buenos Aires Children′s Hospital, C1425EFD, Buenos Aires, Argentina 2. CEGyR (Centro de Estudios en Ginecología y Reproducción), Buenos Aires, Argentina 3. CREA, Medicina de la Reproducción, Valencia, Espa?a
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Abstract: | Fertilization in mammals occurs via a series of well-defined events in the secluded environment of the female reproductive
tract. The mode of selection of the fertilizing spermatozoon nevertheless remains unknown. As has become evident during in
vitro fertilization by sperm microinjection into the oocyte, abnormal spermatozoa can successfully fertilize oocytes. Under
these extreme conditions, post-fertilization events, early embryonic development and implantation are significantly compromised
indicating that the contribution of spermatozoa extends beyond sperm penetration. Microscopic identification of normal spermatozoa
is a well-standardized procedure but insights into the mechanisms that lead to aberrant sperm differentiation and into the
subcellular nature of sperm abnormalities have only recently begun to be obtained. The spermatozoon is the result of a complex
development in which spermatid organelles give rise to various structural components with characteristic functions. Similar
to other differentiated cells, the spermatozoon has a specific pathology that is most clearly identified by ultrastructural
evaluation coupled with immunocytochemistry and molecular techniques. This multidisciplinary approach allows the precise characterization
of sperm abnormalities, including structural, molecular and functional aspects. We summarize here studies of the physiopathology
of spermiogenesis in two abnormal sperm phenotypes of infertile men: dysplasia of the fibrous sheath and acephalic spermatozoa/abnormal
head-tail attachment. The characterization of the abnormalities of the tail cytoskeleton and centrioles has uncovered aspects
of the subcellular basis of pathological spermiogenesis, has suggested experimental approaches to explore the nature of these
anomalies and has opened the way for genetic studies that will ultimately lead to the design of the therapeutic tools of the
future. |
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