Harmful effects of anti-zona pellucida antibodies in folliculogenesis, oogenesis, and fertilization

The zona pellucida (ZP) is an extracellular matrix that surrounds the mammalian oocyte and plays an important role in normal folliculogenesis and fertilization. Because of its strong immunogenicity and its possible relation with premature ovarian failure, we conducted the present study to examine whether or not anti-ZP antibodies impaired folliculogenesis. Mouse preantral follicles were cultured with anti-ZP antibodies to evaluate the effects on follicle growth and antral formation. The cultured follicles were also examined by electron microscope and assessed for oocyte maturation, fertilization capacity, and embryo development. The results showed that follicles cultured with anti-ZP antibodies had a smaller diameter than the controls. Also, these antibodies reduced antral formation, mucification, maturation of oocytes (metaphase II), and fertilization rates. Morphologically, ZP thickness was lower in the anti-ZP antibody groups. The quantity of granulosa cell microvillous processes that transverse the ZP was diminished in follicles cultured with anti-ZP antibodies. In conclusion, anti-ZP antibodies were harmful to the normal development of mouse follicles and oocytes in vitro. These antibodies may be a cause of premature ovarian failure syndrome because they disrupt the gap junctions between the oocyte and granulosa cells and, as a consequence, damage the bidirectional communication necessary for normal folliculogenesis.