Abstract
BackgroundPolycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder characterized by a disruption of follicular growth and anovulatory infertility. In women with PCOS, follicular growth and ovulation can be induced by subcutaneous injections of low doses of follicle stimulating hormone (FSH). The aim of this study was to determine the effect of oral administration of recombinant human FSH (rhFSH) on follicle development in a PCOS murine model. Moreover, since it is unlikely that intact rhFSH is present into the circulation after oral administration, the biological activity of a peptide fragment, derived from the predicted enzymatic cleavage sites with the FSH molecule, was investigated in vitro on cumulus-enclosed oocytes (COCs).MethodsFemale peripubertal mice were injected with dehydroepiandrosterone (DHEA) diluted in sesame oil for 20 consecutive days and orally treated with a saline solution of rhFSH. A control group received only sesame oil and saline solution. At the end of treatments, blood was analyzed for hormone concentrations and ovaries were processed for morphological analysis. The presumptive bioactive peptide was added during in vitro maturation of bovine COCs and the effects on cumulus expansion and on maturation rate were evaluated.ResultsDHEA treatment increased serum levels of testosterone, estradiol and progesterone as well as the percentage of cystic follicles. Orally administered rhFSH restored estradiol level and reduced the percentage of cystic follicles. Despite these results indicating a reduction of the severity of PCOS in the mouse model, the presumptive bioactive peptide did not mimic the effect of rhFSH and failed to induce bovine cumulus expansion and oocyte maturation in vitro.ConclusionsAlthough further studies are needed, the present data supports the concept that orally administrated FSH could attenuate some of the characteristic of PCOS in the mouse model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0192-9) contains supplementary material, which is available to authorized users.
Highlights
Polycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder characterized by a disruption of follicular growth and anovulatory infertility
Because of the large number of small antral follicles that are sensitive to follicle stimulating hormone (FSH) [15], women with PCOS have a higher risk in developing ovarian hyper-stimulation syndrome (OHSS) in response to FSH treatment [16]
Before treatment the body mass of Morphological evaluation of ovaries To study the potential role of the oral administration of low doses of recombinant human FSH (rhFSH) on follicle development in DHEAtreated animals, the number of follicles 150–300 μm in diameter and of follicles >300 μm in diameter was monitored in each ovary
Summary
Polycystic Ovary Syndrome (PCOS) is a widespread reproductive disorder characterized by a disruption of follicular growth and anovulatory infertility. In women with PCOS, follicular growth and ovulation can be induced by subcutaneous injections of low doses of follicle stimulating hormone (FSH). Because of the large number of small antral follicles that are sensitive to FSH [15], women with PCOS have a higher risk in developing ovarian hyper-stimulation syndrome (OHSS) in response to FSH treatment [16]. To reduce this risk, low-dose administrations of injectable FSH have been used [17, 18]. The most appropriate regime is the step-up protocol, in which the FSH dose is gradually increased until follicular development is observed, and maintained until follicular selection is achieved [19, 20]
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