From precocious puberty to infertility: metabolic control of the reproductive function

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Background

The existence of a fundamental link between nutrition and reproduction is well established. It is known for decades that a critical amount of stored energy is required for sexual maturation and maintenance of fertility. This concept is based on the idea that when survival is threatened by scarcity of food or increased energy demands, male and female of most species divert energy away from reproduction. This includes sexual maturation, the production of reproductive hormones and gametes, and the maintenance of pregnancy and lactation. If excessive leanness occurs in young women, puberty is often delayed. On the other hand, excess stored energy also negatively impacts fertility. Elevated adiposity aggravates polycystic ovarian syndrome, ovulatory dysfunctions and may induce hypothalamic hypogonadism in women. In obese men, fertility is usually decreased likely due to altered activity of the hypothalamus-pituitary axis and defective steroidogenesis in testis. Recently, studies have documented the link between the advance of obesity and the increasing rates of “precocious puberty”. In 1997, an epidemiologic study reported that 6.7% of American girls had clinical evidence of puberty at age 7 years, and 14.7% at age 8 years. That study described the youngest ever reported population age at puberty onset of 9.96 ± 1.82 years. In September of 2010, an alarming study showed that this phenomenon has been aggravated in the last decade. The authors found an increment of 5-8% in the number of girls with clinical evidence of puberty at age 7 and 8 years, compared to the 1997 study. They also reported a high correlation of early puberty onset and childhood obesity. These observations suggest the existence of a previously unrecognized deleterious effect of the increasing rates of childhood obesity: “the precocious puberty”, which will bring profound social and health implications for the next generations. Earlier menarche in girls is associated with increased risk of adult obesity, type 2 Diabetes and breast cancer. Thus, changing levels of key metabolic cues is an essential signal for the onset of puberty and maintenance of the tone of the reproductive system. As the activity of gonadotropin releasing hormone (GnRH) neurons is essential for the development and maturity of the reproductive axis, efforts have been made to identify the factors that directly regulate the activity of GnRH neurons. For example, sensory signals and metabolic cues (e.g. glucose) may reach the reproductive control sites of the central nervous system via sensory inputs conveyed by the vagus nerve or by direct action in the caudal brainstem. In addition, circulating metabolic factors such as leptin, insulin and ghrelin also inform the brain about the individual nutritional state. The goal of this Research Topic is to assemble multidisciplinary specialists to provide up-to-date reviews on the recent advances and achievements in the field.

ILLUSTRATION: Neurons expressing Kiss1 and estrogen receptor alpha in the preoptic area

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