Paolo Giovanni Artini

Preovulatory human follicular fluid in vitro inhibits interleukin (IL)-lα, IL-2, and production and expression of p55 chain IL-2 receptor of lymphomonocytes

OBJECTIVEnTo evaluate the immunoactivity of human follicular fluids (FFs) of ovaries stimulated with exogenous gonadotropins.nnnPARTICIPANTSnFollicular fluids and peripheral blood mononuclear cells (PBMCs) were obtained at the time of ovum pick-up from 15 women (25 to 34 years of age) undergoing gonadotropin stimulation for GIFT.nnnMETHODSnThe evaluation of the blastic response of PBMC to phytohemagglutinin (PHA), PHA plus recombinant interleukin (IL)-2, and recombinant IL-2 alone was performed by measuring 3H-thymidine (3H-TdR) incorporation by the cells cultured in media with or without FF. The percentage of CD25 expression on PHA-stimulated T lymphocytes was evaluated by flow cytofluorometry. The levels of IL-1 alpha and IL-2 in supernatants from PHA-stimulated PBMC were evaluated by an ELISA.nnnRESULTSnThe PBMC blastic response to PHA, to recombinant IL-2 alone, and to PHA plus recombinant IL-2 was suppressed by the addition of FF. However, the percentage of inhibition of 3H-TdR incorporation induced by FF in cultures performed in the presence of PHA alone was significantly higher than that obtained in cultures performed in the presence of PHA plus recombinant IL-2. The percentage of expression of the CD25 on PHA-stimulated lymphocytes was also significantly lower in presence of FF in comparison with the controls. Similarly, the production of IL-1 alpha and IL-2 in culture media of PHA-stimulated PBMC was significantly lower when FF was added in culture medium.nnnCONCLUSIONSnThe present data confirm that preovulatory FFs obtained by gonadotropin-stimulated ovaries contain unknown factors that induce immunosuppression. Furthermore, our study explains that the immunosuppressive activity of FF is mediated by the specific inhibition of the production of IL-1 alpha and IL-2 and by the decreased expression of the CD25.

IMPROVEMENT OF OVARIAN RESPONSE TO INDUCTION OF SUPEROVULATION WITH COMBINED GROWTH HORMONE­ GONADOTROPIN TREATMENT

Recent in vitro data suggests that growth hormone (GH) and several peptide growth factors take part in the regulation of ovarian activity (Dorrington et al., 1987, Gospodarowicz et al., 1979; Jia et al., 1986; Knecht et al., 1983; Mondschein et al., 1984 and 1988; Schomberg et al., 1983). Among them, insulin-like growth factor-I (IGF-I) is the most studied in its role in modulating the growth and differentiation of the components of ovarian follicle. IGF-I has been shown to exert a strong stimulatory effect on the proliferation (Savion et al., 1981; Baranao et al., 1984) and the differentiation of granulosa cells (Baranao et al., 1984; Adashi et al., 1984 and 1986). Furthermore, the role of IGF-I in amplifying the action of gonadotropins on ovarian tissue, has been evidenced in the rat (Adashi et al., 1985). On the other hand, administration of GH in hypophysectomized estrogen-treated female rats increased the ovarian tissue IGF-I content (Jia et al., 1986). In vivo studies demonstrated that exogenous administration of GH is followed by an increase of the levels of plasma IGF-I in humans (Zapf et al., 1978).