Postnatal ovarian follicle development in hypogonadal (hpg) and normal mice and associated changes in the hypothalamic--pituitary ovarian axis

Abstract

Significant uterine growth occurred in normal and hypogonadal (hpg) mice between Days 7 and 21 but thereafter no further growth was observed in hpg mice. The ovaries of hpg mice were significantly smaller than those of normals at all ages, but there was no significant difference between the number of non-growing follicles in the ovaries of mutants and their normal littermates at any age studied, and normal and hpg mice showed a marked reduction in the number of non-growing follicles during the first month of life. The size and composition of the growing follicle population in hpg mice, however, differed markedly from those in normal animals and by 21 days of age the number of growing follicles in mutants was significantly reduced. There was no significant difference in the number of Type 3b follicles before 60 days of age, but the number of all other follicle types was significantly less in hpg mice at all ages studied. Follicles in which the antrum is fully developed (Type 7 and 8) were never seen in the ovaries of mutants and corpora lutea were never observed. Interstitial tissue development was also very poor in hpg ovaries. The hypothalamic GnRH content in normal mice remained low until Day 20, before rising sharply to adult levels (approximately 800 pg) between Days 20 and 30. The pituitary FSH content increased over the first 10 days of life to reach a peak of about 5000 ng, before declining to the adult value of about 2000 ng by Day 30, whilst the plasma FSH concentration was high in the first 10 days, but fell to adult levels over the next 20 days. Pituitary LH content increased significantly between Days 5 and 10 to reach the adult level of about 600 ng. Hypothalamic GnRH was undetectable at all ages in hypogonadal mice, but the pituitary content of FSH and LH had risen to the attenuated mutant adult value by Day 15, and unlike normals, plasma FSH concentrations were not elevated during the neonatal period. These results suggest that minimal gonadotrophic stimulation of the ovary from birth has no effect on the total number of follicles but reduces the number of growing follicles and prevents follicle growth beyond the early antral stage. Gonadotrophins therefore appear to have a role in the initiation and continuance of follicle growth in the adult mouse.

Ovarian steroid metabolism during post-natal development in the normal mouse and in the adult hypogonadal (hpg) mouse

“…At 38 days of age corpora lutea are present in 50% of mice of the strain used in this study (Halpin et al, 1986) and this coincides with an increase in 20a-HSD activity which is sustained up to 60 days. It seems likely, therefore, that 20a-HSD activity in the mouse ovary is also associated primarily with the corpus luteum.…”

“…There was a peak in 5a-reductase activity in the mouse ovary between 7 and 38 days judged by the accumulation of 5a-reduced C21 steroids. This was reflected, however, in only low levels of androstanediol which peaked between 29 and 38 days, the time at which ovulation can first be observed in this strain of mouse (Halpin et al, 1986 5a-pregnane-3ct-ol-20-one and 5a-pregnane-3a,17a-diol-20-one (Karakawa et al, 1976;Inaba et al, 1978). High levels of 5a-pregnane-3-ol-20-one are formed in the mouse but it does not appear to act as a substrate for C17-C20 cleavage in this species.…”

“…The animals were derived originally from F, hybrids of two inbred strains C3H/HeH and 101/H (Cattanach et al, 1977). The day of birth was designated as Day 0 and animals were used for experiment when aged 7,21,29,38 and 60 days, ages previously used for morphological studies in this strain (Halpin et al, 1986).…”

“…Kraiem & Samuels (1974) have measured changes in the activity of some steroidogenic enzymes in the ovaries of 25-day-old animals after gonado¬ trophin treatment. In this study we have examined changes in the overall pattern of steroid metabolism in the mouse ovary during development using a mouse strain in which the pattern of post-natal follicular development is known (Halpin et al, 1986). We have developed a combination of thin-layer chromatography (t.l.c.)…”

Follicular assembly: mechanisms of action

“…FSH is present in the serum of neonatal mice and hamsters (Vomachka & Greenwald 1979, Halpin et al 1986) and the FSH receptor is detected using RT-PCR in neonatal mouse ovaries (O'Shaughnessy et al 1994). Inactivation of FSH using an anti-FSH antibody results in the inhibition of primordial follicle formation in the hamster (Roy & Albee 2000), while addition of FSH to cultured ovaries results in acceleration of primordial follicle formation (Wang & Roy 2004).…”