engleski

The ovary during human fetal development

Although a complete human ovarian development occurs only at puberty, when the ovary expresses its cyclically steroidogenic activity, the follicular development is limited to organogenesis. The process of ovarian organogenesis entails three overlapping stages of gonadal morphogenesis, primary sex differentiation and definitive ovarian histogenesis. Folliculogenesis begins at the beginning of the definitive histogenesis ( approximately at 15th - 16th weeks of fetal development) and continues until total depletion of sex cords (around the sixth to the eighth month of postnatal life). The folliculogenesis is the most crucial period of human ovarian organogenesis in which the fertility and the duration of female reproductive life span are determined (1). The aim of this study was to determine the dynamic of ovarian growth during human fetal and postnatal development by applying morphological and morphometric methods (stereology). We also wanted to evaluate the follicular spatial position during definitive ovarian histogenesis. Twelve left ovaries from ten fetuses (14-37 weeks of development) and two infants in the 1st and 2nd postnatal months, free of malformations of the genital system have been invstigated. Ovaries were fixed in 4% buffered paraformaldehyde, embedded in toto in paraffin wax and processed for morphological and stereological analyses. Ovarian serial sections of 7µ m were stained with hematoksilin and eosin. Ovarian volume was calculated by the Cavalieri method (2). During the 14th to 20th weeks of fetal development the average ovarian volume (n=5) was 201 mm3. The ovarian cortex, made up of sex cords, dominated. The cords, connected with surface epithelial cells, consisted of light (oogonia and primary oocytes) and dark regions (somatic cells). The origin of somatic cells is still unclear (3, 4, 5). The outer cortical part showed numerous oogonia in mitosis. The middle and the deepest cortical region (above the medulla) contained primordial follicles surrounded with mesenchyme. Small blood vessels (capillaries) run vertically towards the outer cortical surface. The mesenchyme of ovarian medulla contained arteries and veins. In hilus of all 5 analysed fetal ovaries we found rete ovarii, derived from the mesonephric tubules. During the 22nd to 28th weeks of fetal development the average ovarian volume ( n=3) was 341.5 mm3. The outer ovarian surface became wrinkled. The cortex still dominated and the medulla was comparatively small. Beneath surface epithelial cells we again found accumulations of light cells but follicles missed. This part of ovarian cortex will later differentiate in tunica albuginea. Follicles were more numerous compared with the earlier developmental stage. Cortical middle part contained primordial and primary follicles. In the inner cortical regions we found few unilaminar and multilaminar primary follicles and two antral follicles surrounded with theca folliculi. Bigger blood vessels and nerves passed through inner and middle cortical regions. Medulla still contained rete tubules, lined with simple columnar epithelium. During the 37th week of fetal development and in two postnatal months the average ovarian volume (n=4) was 595 mm3. Ovarian cortex was thinner and medulla dominated compared with the earlier stages of development. Just beneath the surface epithelial cells dense connective tissue formed tunica albuginea. Middle cortical region consisted of smaller number of primordial follicles.Numerous primary follicle, a few preantral and 9 antral follicles were situated at the cortico-medullar junction. In postnatal ovaries was very difficult to recognize the cortico-medullary boundary because of abundance of scattered tissue and remnants of atretic follicles. The rete were still present at medulla. During definitive histogenesis the ovarian volume progressively increased. Single ovarian volumes calculated with Cavalieri method, were 80-850 mm3. This 10-fold enlargement of the ovary is analogous to the dynamic of growth estimated for other fetal organs (6). However, our measurements of human fetal and postnatal ovaries have confirmed that each fetal organ has significant individual and inter-individual variabilities. REFERENCES: 1. Sforza, C., Ranzi, A., Ferrario, V.F., Forabosco, A. 2004. Growth patterns of human ovarian volume during intrauterine and postnatal organogenesis. Early Hum Dev 80:7-17. 2. Cruz-Orive, L.M., Weibel, E.R. 1990. Recent stereological methods for cell biology: A brief survey. Am J Physiol 258:L148-L156. 3. Satoh, M. 1991. Histogenesis and organogenesis of the gonad in human embryos. J Anat 177:85-107. 4. Motta, P.M., Makabe, S., Nottola, S.A. 1997. The ultrastructure of human reproduction. I. The natural history of the female germ cell: origin, migration and differentiation inside the developing ovary. Hum Reprod Update 3:281-295 5. Löffler, S., Horn, L- C., C., Weber, W., Spanel-Borowski, K. 2000. The transient disappearance of cytokeratin in human fetal and adult ovaries. Anat Embryol 201:207-215. 6. Deter, R.L., Rossavik, I.K., Cortissoz, C., Hill, R.M., Hadlock, F.P. 1987. Longitudinal studies of thigh circumference growth in normal fetuses. J Clin Ultrasound 15:388-393.

human fetal ovary; development; stereology

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