Pre-testicular causes of male infertility

By BSc, MSc (embryologist) and BA, MA (fertility counselor).
Last Update: 07/23/2014

Sperm is formed thanks to an auto-regulated complex hormone system that starts in the brain and ends in the testis. The way sperm is generated resembles, to a certain extent, to process of egg generation.

Spermatozoa are formed thanks to a complex hormonal system, an auto-regulated process that starts in the brain and finishes in the the testicle.This system is similar, to a certain extent, to the egg generation system. To understand what is altering the proper formation of spermatozoa, we need to take a look on the structures involved.

The different sections of this article have been assembled into the following table of contents.

Hypothalamic–pituitary–gonadal axis

The hypothalamus secretes a hormone called GnRH, that has receptors in the pituitary, a small neuroendocrine gland (organ where nervous orders, neurons and hormonal signals blend), that secretes the hormones required to sperm production, as well as the FSH (follicle stimulant hormone) and the LH (lutein hormone) in women. The two hormones regulate ovulation and menstrual cycle.

Regarding the testicle, the spermatogonia are sperm stem cells, although there are other cells essential for the process, regulating it and stimulating a proper hormonal communication. In broad terms, these cells are:

  • Leydig cells: segregate testosterone when they receive LH from the brain. This is necessary for sperm formation.
  • Sertoli cells: support cells, when they receive FSH they act on Leydig's to increase testosterone segregation.
  • Germinal cells: spermatogonia are stem cells whose divisions will produce spermatozoa, but they need hormonal stimulation to do it.

When there is enough testosterone, it travels to brain through the bloodstream to tell him to stop secreting, because they are stocked. That is how GnRH and FSH secretion is regulated, keeping proper hormonal levels for sperm formation. Everything is coordinated.

Hormonal levels that alter testis function

The hormonal process has to be perfectly adjusted so that the signals sent will turn into spermatozoa. Some hormone alterations that may affect are:

  • Hypogonadism hypogonadotropic: all hormonal levels are diminished, the hormones of the pituitary and testicles do not have the required levels of proper testicular function. The problem may lay on the alterations in the hypothalamus and/or pituitary. There is a hereditary alteration of the hypogonadism hypogonadotropic called Kallmann Syndrome, in which patients may also present anosmia.Treatment will depend on the origin of the problem, but it can be solved with hormone replacement therapy, stimulating testicular action and increasing sexual hormone levels.
  • Hypergonadotropic Hypogonadism: The hypothalamus and pituitary work correctly, but as much as FSH it secretes, the Leydig cells are not able to generate enough testosterone, proper sperm production is not achieved. The problem lays on the endocrine cells of the testicle.The brain does not notice there is enough FSH and keeps secreting it, therefore FSH levels are high and testosterone and inhibin low. The testicles can be small, reflected by oligo or azoospermia. The treatment contemplate the direct application of testosterone, given that is it not necessary to stimulate the testicle, as brain FSH and LH production is appropriate.

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Authors and contributors

 Cristina Mestre Ferrer
Cristina Mestre Ferrer
BSc, MSc
Bachelor's Degree in Biological Sciences, Genetics & Human Reproduction from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Embryologist at IVI Barcelona. More information about Cristina Mestre Ferrer
Adapted into english by:
 Sandra Fernández
Sandra Fernández
Fertility Counselor
Bachelor of Arts in Translation and Interpreting (English, Spanish, Catalan, German) from the University of Valencia (UV) and Heriot-Watt University, Riccarton Campus (Edinburgh, UK). Postgraduate Course in Legal Translation from the University of Valencia. Specialist in Medical Translation, with several years of experience in the field of Assisted Reproduction. More information about Sandra Fernández

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