Evaluation of the protective effect of GnRHa on Cy-induced follicular depletion.

<p>The follicular population was evaluated by counting all follicles in every fifth section of whole serial sectioned ovaries of mice injected daily with 500μg/kg of GnRH agonist or antagonist subcutaneously for 21 days and treated with 200mg/kg of Cy on day 15. The different conditions are control, Cy alone (Cy), GnRH agonist alone (Ago), or with Cy (Ago + Cy) and GnRH antagonist alone, (Ant) or with Cy (Ant + Cy). Results are expressed as mean ± SD, *p < 0.05 compared with controls. Statistical difference was observed between Cy-treated groups and control but not with GnRHa treatments.</p

Total follicular depletion, and proportion of resting and growing follicles population per ovary according to the Cy doses in mice.

<p>Results are expressed as mean ± SD. N = number of ovaries analysed.</p><p>*p < 0.05 compared with controls.</p><p>Total follicular depletion, and proportion of resting and growing follicles population per ovary according to the Cy doses in mice.</p

Inhibitory effect of GnRHa on follicular development.

<p>(a) The oestrus stages were determined by evaluating the vaginal cytology (pro-oestrus (P), oestrus (E), metoestrus (M) and dioestrus (D). The oestrus cycle is partially blocked according to the type of GnRHa, irrespective to the dose. Here oestrus cycle during treatment with antagonist 20μg/kg, agonist 2μg/kg and agonist im 4mg/kg are represented (b) The growing follicles ratio was evaluated by counting follicles in every fifth section of each whole serial sectioned ovary from different experimental conditions (2, 20, 200 or 500 μg/kg/day or im agonist injection of 4mg/kg). Results are expressed as mean ± SD. (c) Representative immunohistological sections showing growing follicles (stained with KI-67) without apoptosis staining in granulosa cells (TUNEL) after 15 days of GnRHa treatment. Scale bar = 100 μm. (d) Serum FSH levels (ng/ml) according to the doses and injection site of GnRHa. Each symbol represents one animal.</p

Correlations between immune responses per study arm.

Correlations were analysed at 28 days after the second vaccine dose between SARS-CoV-2 anti-RBD IgG binding antibodies and SARS-CoV-2 Wuhan neutralizing antibodies (A), and between SARS-CoV-2 Wuhan and Delta variant neutralizing antibodies (B). Pearson correlation coefficients (95% CI) are given per study arm. Ellipses represent the 95% CI for the two study arms (purple = 20μg, black = 30μg), assuming multivariate normal distributions. NT50 = 50% neutralizing antibody titre, RBD = SARS-CoV-2 receptor binding domain, BAU = binding antibody units.</p