On the Problem of Female Infertility: A Search for Genetic Markers

Resumo

In one of every ten cases, the reason behind female infertility turns out to be an orphan disease called hypogonadotropic hypogonadism, the only symptom of which is a reduced level of gonadotropins and, as a consequence, amenorrhea in females. Most often, hypogonadotropic hypogonadism is caused by disorder in the secretion of gonadoliberin, a product of the GNRH1 gene. However, the disease is heterogeneous one, so it may originate from either genetic or nongenetic causes. To study the genetic component of the disease pathogenesis, we conducted molecular-genetic analysis of 11 candidate genes controlling the synthesis and secretion of gonadoliberin, as well as several candidate genes functioning as neurodevelopment and neuroendocrine regulators. The study included a group of patients afflicted by hypogonadotropic hypogonadism of an isolated form (n = 10) and a control group of healthy women (n = 20). All women were of reproductive age, with no detected mutations in candidate genes that could cause any pathological effect. The data on candidate genes expression in white blood cells are indicative of an increased expression of the GNRH1 gene in the sampled patients as compared to the control group (p < 0.05). Other genes demonstrate heterogeneous expression in both the patients group and the control group. Thus, increased GNRH1 expression in blood cells appears to be associated with the isolated form of hypogonadotropic hypogonadism and may be used in the future as a disease marker.