Neuron activation near brain base due to stress may lead to infertility in women

Infertility is a reproductive health problem that millions across the world face. According to estimates by the World Health Organisation (WHO), around 186 million individuals live with infertility currently. The most common causes of infertility in women are abnormalities in the ovaries, uterus, fallopian tubes and endocrine system. Among men, they include low motility, absence, low levels or abnormal shape of the semen and problems in ejection. Apart from these physiological causes, infertility is also linked to psychological causes.

Infertility and stress, a two-way link

Studies published over the last few decades have progressively thrown more light on the psychological aspects of infertility. For example, a study published in the Journal of Psychosomatic Obstetrics & Gynecology in 1993 suggested that psychological symptoms associated with infertility are similar to those associated with conditions like cancer, heart attack and hypertension. This study also indicated that the anxiety and depression scores of women with infertility were lower only compared to HIV/AIDS and chronic pain patients, highlighting the severity of the stress associated with infertility.

However, as a study published in 2018 in Dialogues in Clinical Neuroscience points out, most studies are unable to explain the exact causal relationship between stress and infertility. Does infertility cause stress or does stress cause infertility? More and more studies have focused on the former part of this link rather than the latter and the fact that infertility does cause stress has been conclusively established. When it comes to whether stress can cause infertility or not, the findings of a recent study in The Journal of Neuroscience are illuminating.

Neuronal pathways between stress and infertility

The study, conducted by researchers at the University of Otago’s Centre for Neuroendocrinology, set out to confirm via laboratory testing that psychosocial stress can lead to negative outcomes for the reproductive system and thereby cause infertility. The researchers specifically studied the alterations in RF-amide related peptide-3 (RFRP-3) — a mammalian gonadotropin-releasing hormone that regulates environmentally mediated reproductive behaviour — at the base of the brain to evaluate this connection between stress and infertility.

The researchers used a mouse model to investigate if the alterations in RFRP-3 neuronal activity led to changes in puberty onset, fertility and stress responses. They used transgenic techniques to selectively reduce, stimulate or inhibit RFRP-3 neurons in order to understand its physiological roles in the regulation of fertility. They found that chronic activation of RFRP-3 (which occurs in cycles according to normal mammalian reproductive function and requirements determined by genetic and other factors) delayed male puberty onset and female reproductive cycle progression, but did not affect fertility as such. However, when activated due to exposure to the stress hormone cortisol, the researchers observed that increased RFRP-3 production led to acute and chronic stress-induced reproductive suppression.

This stress-induced reproductive suppression due to increased production of RFRP-3 was more significant in women. This way the researchers were able to find a direct and causative link between RFRP-3 neuronal function, hormonal-stress axis and the reproductive system functions. Their data, therefore, clearly indicates that there’s a neuronal and cause-and-effect link between stress and infertility, especially among women. Further experimentation revealed to them that pharmacologically blocking the receptors that acted on RFRP-3 secretion could potentially provide a method of overcoming clinical infertility due to stress, anxiety or affective disorders.

For more information, read our article on Infertility .

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