title: Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice.
abstract: Ovarian primordial follicle reserve is considered hormonally independent or subject to depletion by FSH-driven follicle recruitment. To explore specific in vivo effects of FSH on early follicle populations in the absence of luteinizing hormone (LH) activity, we examined mature hypogonadal (hpg), gonadotrophin-deficient mice expressing transgenic (tg) human FSH. Sustained expression of tg-FSH (5.3 +/- 0.3 IU/l) increased ovary weights fourfold and significantly elevated total primordial follicle numbers twofold in tg-FSH hpg (4209 +/- 457) relative to non-tg hpg (2079 +/- 391) and wild-type (2043 +/- 195) age-matched ovaries. Absolute primary follicle numbers in tg-FSH hpg ovaries were similar to non-tg hpg and wild-type ovaries. Furthermore, tg-FSH quantitatively increased secondary and antral follicles in hpg ovaries to numbers equivalent to wild-type, but did not induce ovulation, indicating a selective FSH response without LH. Circulating inhibin B and inhibin A levels were significantly increased in tg-FSH hpg females compared with hpg controls, and inhibin B correlated with antral number, consistent with FSH-driven antral follicle formation. These findings revealed that sustained pituitary-independent FSH activity, in the absence of endogenous gonadotrophins, promotes an increase in primordial follicle reserve despite also stimulating follicular growth in mature females. Therefore, the tg-FSH hpg ovary presents a novel paradigm to evaluate specific gonadotrophin effects on follicle reserve and recruitment.
authors.affiliation: Andrology Laboratory, ANZAC Research Institute, University of Sydney, Concord Hospital, New South Wales 2139, Australia. charles@anzac.edu.au
authors.forename: C M
authors.initials: CM
authors.lastname: Allan
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Jimenez
authors.forename: B
authors.initials: B
authors.lastname: Marshan
authors.forename: J
authors.initials: J
authors.lastname: Spaliviero
authors.forename: P
authors.initials: P
authors.lastname: Illingworth
authors.forename: D J
authors.initials: DJ
authors.lastname: Handelsman
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000378:metabolism*; D007265:Inhibins / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000033:anatomy & histology
chemical_list: C422362:inhibin A; C422364:inhibin B; D007987:Gonadotropin-Releasing Hormone; D007265:Inhibins; D005640:Follicle Stimulating Hormone