Fetal growth retardation as a cause of impaired ovarian development
J. P. de Bruina, M. Dorlanda, H. W. Bruinsea, W. Splietb, P. G. J. Nikkelsb and E. R. Te Veldea
Low birthweight has been associated with diseases and disorders later in life. It has been suggested that this is caused by the impaired development of abdominal organs, especially in cases of growth retardation. Besides general malnutrition of the fetus, preferential bloodflow to the heart and brain may further deprive organs, such as liver, pancreas and kidney, of nutrients. As a result these organs may not develop properly. Anatomically, the ovary is situated close to the kidney and it is very likely that, similar to the kidney, ovarian development can be negatively affected by intra-uterine growth retardation. Placental insufficiency, which is an important cause of severe intra-uterine growth retardation, was used as a model to investigate this hypothesis. In the present study, the volume percentages of primordial follicles in the ovaries of four severely growth-retarded fetuses of different gestational ages are compared to those of four age-matched controls. It is found that these volume percentages in growth-retarded fetuses were significantly lower than those observed in the age-matched controls. It can be concluded that ovarian development is impaired in intra-uterine growth-retarded fetuses. These findings further suggest that, as a result of the premature loss of follicles, females with low birthweights may encounter fertility problems later in life.
Morphometry of human ovaries in normal and growth-restricted fetuses
J. P. de BruinCorresponding Author Contact Information, E-mail The Corresponding Author, a, P. G. J. Nikkelsb, H. W. Bruinsec, M. van Haaftena, C. W. N. Loomand and E. R. te Veldec
According to the fetal origins hypothesis, normal growth and development of abdominal organs is disturbed by intra-uterine growth restriction, leading to diseases later in life. The aims of this study were to investigate the effect of growth restriction on the ovaries of human fetuses and to investigate the dynamics of follicular growth in normal fetuses. We selected 21 normal female fetuses (controls) and seven severely intra-uterine growth-restricted female fetuses (IUGR cases) from all autopsy records over a 10-year period. Ovarian volume was calculated and from histological sections the volume-percentage of follicles in the ovarian cortex, the maximum diameters of individual follicles and the distribution of the follicle classes and oogonia were determined. The volume of the ovaries increased significantly from 0.10 to 0.36 cm3 in the second half of gestation. The mean volume-percentage of ovarian follicles and the mean follicle diameter significantly increased with 0.48% and 0.52 μm per week, respectively. Class B/C (intermediary) follicles (72%) were predominantly present. Class B (primordial) follicles decreased from over 20% to less than 10% and class C (primary) increased from 6 to 19%. Class A (oogonia) were frequently present before 30 gestational weeks, but were rare after that age. For all studied parameters we did not find differences between IUGR cases and controls. Intra-uterine growth restriction does not seem to disturb ovarian development in the human fetus. In the second half of gestation the follicle pool increases by the growth of individual follicles, the transition of follicle to larger classes, and probably by increasing follicle numbers. As most follicles at term were class B/C and C, follicles up to class C are probably part of the resting stock.
Aspects of Ovarian Follicle Development throughout Life, N.S. Macklon, B.C.J.M. Fauser
The pool of primordial follicles present in the female ovary reaches its maximum number around 20 weeks of gestational age and then decreases in a logarithmic fashion throughout life until complete depletion occurs around the age of the menopause. Reproductive life is initiated when less than 10% (0.5 million) of primordial follicles are left. The entire growth trajectory of the follicle takes at least 3 months. Follicle growth up to the antral stage occurs during fetal life and infancy. While the role of gonadotropins in early follicular development remains controversial, the last 2 weeks of development are FSH dependent. The intercycle rise in FSH and decreasing levels thereafter are crucial for recruitment of a cohort of healthy, early antral follicles and subsequent single dominant selection. Following puberty, anovulation may persist for years and this may presage the development of adult anovulatory infertility. The menopause is preceded by a period of reduced fertility. The development of reliable and sensitive markers for ovarian ageing will be the challenge of the near future.