A major breakthrough in androgenetics has been reached through consortia-based efforts. Despite progress, until 2021, the number of genes, which could be included in a diagnostic gene panel for idiopathic NOA patients, was still relatively low (approx. Thanks to the widespread diffusion of next-generation sequencing (NGS)-based whole exome sequencing (WES) or gene panel sequencing a growing number of promising NOA candidate genes have been identified. Given that spermatogenic process is inherently complex and >3000 genes participate in it, a high genetic heterogeneity seems to be plausible. Given that after a complete diagnostic workup, in about 40% of NOA the aetiology remains unknown, it is highly likely that a proportion of these cases will be of genetic origin. Candidate gene mutation screening is performed in Congenital Bilateral Absence of Vas Deferens (CFTR gene) and in Congenital Hypogonadotropic Hypogonadism (35 candidate genes). For instance, in patients with primary testicular failure karyotype abnormalities and Azoospermia Factor (AZF) microdeletions are routinely screened. In all these etiological categories, we can test for known genetic factors. The etiology of this condition can be divided into three major categories: (i) hypothalamic–pituitary axis dysfunction, (ii) primary quantitative spermatogenic disturbances, and (iii) urogenital duct obstruction. PC03 Genetic testing of azoospermia: what is new?ĭepartment of Biomedical, Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, ItalyĪzoospermia occurs in about 1% of men in the general population. Thus, the legacy of undescended testis depends on the need of orchiopexy and whether only one or both testes are cryptorchid. Testosterone and LH levels are not affected by cryptorchidism, indicating normal Leydig cell function. Serum levels of FSH are higher in boys with a history of cryptorchidism than in controls, whereas inhibin B levels are lower in boys with bilateral orchiopexy than in controls. Testes that do not descend spontaneously grow slower and end up smaller than those that descend either normally before birth or spontaneously during mini-puberty. Consequences of cryptorchidism appear in puberty when the testes grow to an adult size. Cryptorchidism is also associated with an increased risk of testicular cancer. Early orchiopexy is recommended to prevent germ cell loss. Germ cell development is impaired in cryptorchid testes due to too high temperature. Reasons of cryptorchidism remain unknown in most cases, although we do know many causes, such as androgen insensitivity and impaired androgen biosynthesis. Later during childhood, new cases appear when testes can ascend to cryptorchid position, which is called acquired cryptorchidism. The incidence of undescended testis in newborn boys varies from 2% to 9%, and 50–75% of these descend spontaneously during the first few months after birth (mini-puberty). Collectively, by highlighting the importance of evolutionary history on human reproductive disease, our data emphasize the usefulness of comparative biology as an ancillary tool in clinical genetics. By genetically interfering with this program in animal models such as fruit flies (Drosophila melanogaster) and mice (Mus musculus), and correlating this information with whole exome sequencing data of infertile men, we uncover 164 previously unknown spermatogenesis genes and three new genetic causes of human infertility. Through network analysis of spermatocyte transcriptomes, we provide evidence that old genes serve as a genetic scaffold from which complexity has evolved, and identify an ancient core module of 79 functional interactions central to the identity of a male germ cell. In this talk, we show that the gene expression program of animal male germ cells has an old evolutionary origin shared between vertebrate and invertebrate species. A key, and largely unexplored, aspect in this topic is the possibility that male germ cells have retained an evolutionarily conserved genetic basis. This often serves as an argument to question if animal models can actually provide meaningful insight into human spermatogenesis. Male germ cell development is typically regarded as divergent across species. EAA POST-GRADUATE COURSE: UPDATE ON MALE REPRODUCTION PC01 Ancient origins of male infertility
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