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Development of Gonads The primordial germ cells are the common origins of spermatozoa and oocytes and thus represent the ancestors of the germline. Like all other somatic cells these are diploid and in human embryos can already be found in the primary ectoderm (epiblast) in the second week. Facilitated through the cranio-caudal curvature and the lateral folding of the embryo, the primordial germ cells wander back into the embryo again between the fourth and sixth week. They move along the yolk sac wall to the vitelline and into the wall of the rectum. After crossing the dorsal mesentery they colonize the gonadal ridge. During their journey, but also while still in the gonadal ridge, the primordial germ cells multiply by mitotic divisions. For both sexes the gonads arise in the gonadal ridges . These are bilateral, ridgelike protrusions that appear ventromedially to the nephrogenic cord. They are generated in the 5th week through the proliferation of the coelomic epithelium and the thickening of the underlying mesenchyma. At this point, the gonadal ridge represents the primitive gonadal primordium. In order for this to develop into the definitive and gender-specific gonads, the immigration of the primordial germ cells is necessary. The testes differentiate themselves earlier than the ovaries, namely in the course of the 7th week 144 days).Responsible for this is the SRY gene on the Y chromosome that induces the development of the testes through the activation of a series of further genes (sex-determining genetic factors and hormones). Development of Testis The differentiation of Sertoli's supporting cells form the first step in the organogenesis of the testes. These cells come - in any case in mice (14) - from pluripotent coelomic epithelial cells of the gonadal ridge. In the gonadal anlage, through the influence of genetic products that are activated by the SRY, they form intercellular membrane connections and in this way surround more and more the primordial germ cells, while growing at the same time as gonadal cords into the medulla. In addition, in a male embryo, cells of mesonephric origin are involved as well in forming the gonadal cords, by accumulating on the outside of the gonadal cords and forming the peritubular myoblasts. From the gonadal cords the testicular cords form that then differentiate to become the convoluted seminiferous tubules (500 to 1000) and straight seminiferous tubules of the mature testicles. The efferent ductules form the connection between the rete testis and mesonephric duct. Towards the end of the 8th week, under the influence of testosterone, the cranial part of the mesonephric duct gets to be tightly coiled and so forms the ductus epididymidis which, outside the epididymis, continues as the deferent duct After the 8th week certain mesenchymal cells between the testicular cords differentiate to become interstitial cells (Leydig), which produce testosterone. The testes thus represent an endocrine gland that produces androgens. The origin of these cells is still unclear – one suspects that a steroid-producing population of cells in the ventral part of the mesonephros differentiate and form both the origin of the adrenal cortex cells and also interstitial cells (Leydig) The mesenchyma between the testicular cords congeals and forms connective tissue septa that subdivide the testicles into lobules In stage this mesenchyma also forms a taut connective tissue layer between the testicular cords and the coelomic epithelium as well as the future tunica albuginea. Finally, the coelomic epithelium transforms itself into a mesothelium, just like the coelomic epithelium around the other serous cavities (peritoneum, pleura, pericardium). Development of Ovary The differentiation of the ovaries happens later than that of the testes, taking place during the 8th week. Since females lack the Y chromosome, they have no SRY gene, except when a translocation of the gene onto the X chromosome occurs!Histologically two regions can be distinguished in an ovary: Cortex, containing all the elements of the parenchyma Medulla, which shares the elements of the stroma with the cortex. In an ovary the majority of the gonadal cords stay in contact with the surface coelomic epithelium. Those gonadal cords that go into the depths out of the thickened coelomic epithelium and lose contact with it atrophy. One also suspects there are signals from the ovary, though, which actively prevent the differentiation into male gonads. So, for example, WNT-4 functions partly as an anti-testis gene in that it suppresses certain developmental steps of differentiation in the direction of the testes Towards the end of the embryonic period one can distinguish the cortex with its gonadal cords and the medullar PGC in the ovary. Although one often finds in the books that cells with a mesonephric origin are also present in the ovarian stroma, examinations made on mice ovaries have shown that no cells migrate out of the mesonephros into the ovary (in contrast with myofibroblasts of the testis) . Probably the cells of the mesonephros only reach the hilus area of the ovary and participate there in the weakly formed rete ovarii. In the course of the 4th month the gonadal cords dissolve - also in the cortex - due to blood vessels that are sprouting from the medulla and isolated cell accumulations surround the oogonia that increasingly divide synchronously (mitosis). Like the spermatogonia the oogonia form similar cell clones. The individual cells are connected with each other via cellular bridges. One can now distinguish various zones in the cortex: In the outermost zone proliferating oogonia are found; somewhat further inward one recognizes oocytes that have spontaneously entered into the prophase of the first meiosis (meiosis 1). From the 5th month a third zone becomes visible towards the medulla in which the oocytes have already completed the prophase of the first meiosis and are surrounded by a monolayer of cells that have differentiated out of the gonadal cord cells and now are now called follicle or granulosa cells. The primary oocytes that are enveloped by follicle cells are now designated primordial follicles and then remain in this stage of the first meiosis (dictyotene stage) Towards the end of the embryonic period one can distinguish the cortex with its gonadal cords and the medullar PGC in the ovary. Although one often finds in the literature that cells with a mesonephric origin are also present in the ovarian stroma, examinations made on mice ovaries have shown that no cells migrate out of the mesonephros into the ovary (in contrast with myofibroblasts of the testis) (. Probably the cells of the mesonephros only reach the hilus area of the ovary and participate there in the weakly formed rete ovarii. In the course of the 4th month the gonadal cords dissolve - also in the cortex - due to blood vessels that are sprouting from the medulla and isolated cell accumulations surround the oogonia that increasingly divide synchronously (mitosis). Like the spermatogonia the oogonia form similar cell clones. The individual cells are connected with each other via cellular bridges. One can now distinguish various zones in the cortex: In the outermost zone proliferating oogonia are found; somewhat further inward one recognizes oocytes that have spontaneously entered into the prophase of the first meiosis (meiosis 1). From the 5th month a third zone becomes visible towards the medulla in which the oocytes have already completed the prophase of the first meiosis and are surrounded by a monolayer of cells that have differentiated out of the gonadal cord cells and now are now called follicle or granulosa cells. The primary oocytes that are enveloped by follicle cells are now designated primordial follicles and then remain in this stage of the first meiosis (dictyotene stage) uring the early fetal period millions of primordial follicles arise through intensive mitotic divisions of the oogonia (the follicle stages from primordial follicle to tertiary follicle). The number of the primordial follicles at birth amount to between 300,000 and 2 million, but they decrease massively from then till puberty. At the beginning of puberty only ca. 40,000 still remain. Of these only ca. 300 primary oocytes develop further between puberty and menopause into fertilizable oocytes.