Requirement for Follicle-Stimulating Hormone Action in the Formation of Primordial Follicles during Perinatal Ovarian Development in the Hamster

Abstract

Whereas FSH action is critical for the growth of preantral follicles, its role in the development of primordial follicles is controversial. The objective of the present study was to evaluate whether perinatal (fetal through early postnatal) FSH action is needed for the formation of primordial follicles, which first appear in the hamster ovary on the 7th to 8th day of postnatal life. A single dose of FSH-specific polyclonal antibody was injected into pregnant hamsters on the 12th, 13th, or 14th day of gestation and into newborn hamsters. Some of the antibody-exposed postnatal hamsters were injected with a single dose of equine CG (eCG) to check the reversibility of the antibody action. Ovaries were collected on D8pn or D12pn, and the percentage of primordial, primary, and secondary follicles was quantitated morphometrically. Ovaries of 8-day-old hamsters that were born to mothers treated with a single s.c. dose of the anti-FSH-antibody on day 12 of gestation had significantly reduced numbers of primordial follicles, compared with those treated with preimmune serum or saline (2.4% vs. 25%); however, the antibody inhibition was nearly completely reversed (approximately 18%) by a single injection of eCG on the first day of life. Delaying antibody treatment during late gestation caused a time-dependent block in granulosa cell differentiation, with a consequent proportional increase in the percentage of primordial follicles. This indicates that FSH-induction of primordial follicle development begins at a critical time of ovarian development. On the other hand, shortening the postnatal duration of eCG exposure reduced the degree of reversal, suggesting that prolonged perinatal FSH action is essential for developing the full gamut of primordial follicles. These results provide the first direct evidence that FSH action during fetal ovarian development is critical for the onset of primordial follicle formation.

Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice

“…Although this stage was considered FSHindependent due to minimal FSH binding (Dunkel et al 1994) or responsiveness (Peters et al 1973, Sokka & Huhtaniemi 1990) and absence of full-length FSH receptor mRNA (Dunkel et al 1994, Rannikki et al 1995, O'Shaughnessy et al 1996 in perinatal mouse or rat ovaries, recent studies suggest that FSH activity may regulate early folliculogenesis before the arrival of laterstage, FSH-dependent growing antral follicles. In hamsters, an early role for FSH in folliculogenesis is suggested by reduced primordial follicle formation after treatment of mothers with FSH-antiserum during late gestation, and expression of full-length FSH receptor mRNA in the fetal ovary as early as day 13 of gestation (Roy & Albee 2000). Neonatal (2-day-old) mice genetically lacking functional FSH receptor exhibit reduced numbers of early, non-growing follicles (Balla et al 2003).…”

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). A recent study using mouse ovary organ culture also implicates FSH in promoting cyst breakdown and primordial follicle formation (Lei et al 2010).…”

Developmental exposure to environmental endocrine disruptors: Consequences within the ovary and on female reproductive function☆

“…These early events in folliculogenesis are mostly regulated by local growth factors and the predominant ovarian steroid hormones (i.e., progesterone, estrogens, and androgens). The pituitary gonadotropins (FSH and LH) are believed to, at best, exert limited control over the processes of follicular assembly and the primordial-to-primary follicle transition [26,27].…”

“…1). As described above, FSH is proposed to have only a limited role in regulating follicular assembly [26,27]. However, evidence does show that FSH exerts some degree of control over this process.…”

“…However, evidence does show that FSH exerts some degree of control over this process. For example, in the hamster, the administration of an FSH-neutralizing antibody in utero reduces the number of primordial follicles, and this effect can be reversed by gonadotropin replacement [26]. In FSH receptor (FSHR) knockout mice, fewer naked oocytes are present relative to wild-type control animals; moreover, FSHR knockout mice possess a greater number of primary and secondary follicles [27].…”