Identified key mechanism of ovulation in vertebrates

Researchers at the University of Barcelona have identified a key mechanism of ovulation in vertebrates. The study, published in the journal Scientific Reports, of the group Nature, shows that the luteinizing hormone (LH) stimulates the coordinated production of the proinflammatory factors TNFα and PGF2α which lead to oocyte release. The study, led by Josep V. Planas, Associate Professor in the Department of Physiology and Immunology and member of the Institute of Biomedicine of the University of Barcelona, has been carried out with fish ovarian follicles but the results may be important to understand human ovulation and female infertility, due to the marked evolutionary conservation of the mechanism of action of LH in the ovary in vertebrates.

Ovulation is a complex process leading to the release of the mature oocyte from the ovarian follicle. Part of the necessary events for follicle rupture and subsequent expulsion of the oocyte include the weakening of the follicle wall by proteolytic digestion, apoptotic follicle cell death and follicle contraction. This process is induced by LH produced by the pituitary gland, but mechanisms involved in this process were not well known so far.

The research team has studied the process in vitro by using trout preovulatory follicles. Researchers have been able to elucidate some of the factors that regulate this process. “LH has several effects on ovulation. First, it stimulates the production and secretion of the tumour necrosis factor alpha (TNFα), a pro-inflammatory protein, by ovarian follicular cells. Second, the protein TNFα stimulates the local production of prostaglandin F2 alpha (PGF2α), a signaling molecule that acts as mediator in a number of physiological processes and that, in the ovary, stimulates proteolysis, apoptosis, follicle contraction and, finally, ovulation”, Planas explains.

Previous studies in humans suggested that LH requires TNFα and PGFα production to stimulate ovulation, but how this process was orchestrated by LH was not entirely well known. The present study suggests a mechanism that could describe the effects of LH in human ovulation and it may be useful to evaluate human infertility. “Ovulation requires the production of TNFα and PGFα stimulated by LH; therefore, to determine the levels of these two mediators and/or their receptors could be important to indicate alterations in LH response in infertility”, says Planas. “Moreover —adds the researcher—, it will be interesting to evaluate the effects of promoting certain aspects of LH action by potentiating the action of TNFα and/or prostaglandins in order to induce ovulation”.

Next, the research team of the University of Barcelona is interested in deciphering the mechanism underlying the spatially localized and controlled rupture of the follicle wall in one precise location to allow the release of the mature oocyte for successful fertilization.