Introduction - Understanding Spermatogenesis and its impact
“Male infertility” refers to the potential of the generation of a new individual. It is one of the reproductive disorders. Male infertility means problems arise in the reproductive parts of the male person. There are several reasons for infertility in a male. Infertility may refer to the impaired generation of sperm. Reasons for infertility can have different reasons. It also means that they are unable to produce a baby with their female partner. Unable to produce healthy sperm is the general cause of infertility. The problem is either in the generation of sperm or in the generated sperm. That means the generated sperms are weak, immature, abnormally shaped, and immortal which means they have no capability to reach their particular destination. In some conditions, there is not contain enough sperm in the “semen”. Environmental and lifestyle is one of the factors of the male infertility(Gumerova, et al., 2022). Now a day male infertility increases in the United Kingdom due to several reasons .
It has been found that about 7% men are diagnosed with infertility whereas 50% of male infertility arises from a heterosexual couple. It has been investigated that over 50% of sperm count has declined in the last 40 years in the UK(Pillai, and McEleny, 2021). It also found that 10-15 % of men are completely suffering from a lack of sperm. On the other hand, only 7% of men are affected by infertility.
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“Spermatogenesis” is the process by which sperms are developed. In this process, immature rounded sperm “pursue mitosis and meiotic division” successively and a series of metamorpfological changes to produce “spermatozoa”. There are three steps in the process of spermatogenesis. The first stage is the proliferation and differentiation of spermatogonia, the second stage is meiotic division, and the last one is spermiogenesis. This is the process by which simple structured spermatids are converted into a more complex structured spermatozoon. This is the process by which it can produce fertilizing sperm(Zhou, et al., 2019). Various forms of germinating cells are produced through a series of differentiation steps. They are “spermatogonia”, “primary spermatocytes”, “secondary spermatocytes”, “spermatids”, and “spermatozoa” (Sengupta et al.,2019 ). The duration of spermatogenesis has been reported 74 days whereas single cycles are 16 days in the semeniferous tubules.
Figure 1: This picture represents the process of spermatogenesis briefly
Spermatogenesis occurs in the seminiferous tubules in the male sex organ, named the testes. The sperm cells are produced from the wall of the seminiferous tubules. The immature “spermatogonia stem” cell continuously arises from the outer wall of the seminiferous tubules and undergoes a series of differentiation reactions and meiotic and mitotic division to produce spermatids. Thereafter, therarffe sp[acioal type cells called Sertoli cells in the seminiferous tubules from which they take nutrition and become “spermatozoa”, the germ cells of the semen. This process is known as “spermiogenesis”. “Spermatogonia” produced from the outer wall of the seminiferous tubules contain a diploid number of chromosomes in the case of males which is 46 in number. Then this “spermatogonia” undergo mitotic division to give rise to “primary spermatocytes” which also contain 2n chromosomes (Oghbaei et al.,2020). Thereafter, these “primary spermatocytes” start a meiotic division to reduce the chromosome number by half so that the male could maintain the chromosome number of humans constantly. This is the main significance of the meiotic division. “Primary spermatocytes” become “secondary spermatocytes” through the process of second meiotic division. The “secondary spermatocytes” contain a half number of chromosomes which means 23 in number. The “spermatids” are formed again and undergo mitotic division to produce sperm cells, spermatozoa.
The process of “spermatogenesis” is occurred under the influence of the hormone secreted from the anterior parts of the pituitary named, "Follicular stimulating hormone (FSH)”, and “Leutineiging Hormone (LH)”. They are collectively known as “gonadotropins”. “FSH” stimulates the proliferation and differentiation of spermatozoa. “FSH” and “LH” are responsible for the process of spermatogenesis (Talebi, et al., 2022). Whereas “LH” stimulates the secretion of the male reproductive hormone “testosterone”. “Testosterone” is secreted from the “interstitial cells of the Leydig” in the seminiferous tubules. “Gonadotropins-releasing hormone (GnRH)” is secreted from the hypothalamus which in turn stimulated the secretion of “FSH and LH” from the anterior pituitary. Thereby, these hormones stimulate the differentiation and proliferation of the “spermatozoa” in the seminiferous tubules (Bakhtyukov et al., 2022). Receptors for both the hormone “FSH” and “LH” are present on the plasma membrane of the “Sertoli cells” and “Leydig cells” expressed as “FSHR” and “LHR”. This hormone helps to the proliferation of the “spermatogonia” into mature “spermatozoa”. LH is responsible for the maturation of the “spermatids” by the process of “spermiuation” in the Sertoli cells in the seminiferous tubules.
Figure 2: This picture represents the hormonal control of spermatogenesis
Consequences of hormonal therapy
There are several consequences of hormonal therapy in the process of spermatogenesis. The effects are both found negative and positive. Though there are some positive effects of hormonal therapy to induce spermatogenesis there are some other side effects as follows (Cattrini, et al., 2020). Negative and side effects of hormonal therapy in male comprises the development of tiredness while the person taking hormones. Whereas excessive hormonal therapy can cause an impotent male person. Hot flushes and sweating may have appeared frequently as those hormones are also associated with temperature regulation in the body. It has been found that hormonal therapy may cause some development of feminine characteristics such as “gynecomastia” which means the development of rudimentary breasts in the male person. There is also arousal of prostate cancer when someone started hormone therapy. Nowadays doctors prescribe more developed injections to avoid prostate cancer through hormonal therapy. Weight gain is the most common consequence of hormonal therapy (Dutra, et bal., 2019). It has been found that most people become obese when they are taking hormones for the “spermatogenesis process”. Some of their people become irritated as those hormones are responsible for their mental condition also and they also forgot the events. People are suffering from mental diseases like “Dementia”, and “Alzheimer's”. Excessive intake of the testosterone hormone may reduce the bone density of the male. Testosterone is responsible for the development of bone (Bretherton et al., 2019). Excessive testosterone hormone causes the solid bone to be porous and as a consequence, it becomes more fragile. Hormonal therapy also increases heart-associated problems in male people.
Marks of spermatogenesis in tissues
“Spermatogenesis” undergo several stages in humans and it takes 74 days to be complete. This process is found to be in the “Intertitisl Cells of the Leydig” in the seminiferous tubules (Delessard, et al., 2022). There are three stages of spermatogenesis such as proliferative stage, differentiation stage, meiosis, and spermiogenesis. Spermatogonia is the primary germ cell that are responsible for the process of spermatogenesis.
Figure 3: This diagram represents the marks of spermatogenesis in tissues
This picture represents the spermatogenesis are occur in the seminiferous tubules. The first step in the process of spermatogenesis is the generation of spermatogonia from the outer wall of the seminiferous tubules (Kohandani, et al., 2022 ). Then it undergoes a series of mitotic and meiotic divisions to give rise to spermatozoa. The steps of spermatogenesis are comprises the production of primary spermatogonia, secondary spermatogonia, then spermatids, and finally matured spermatozoa.
Factors of infertility
There are so many factors that are responsible for the development of infertility in men. If a person often takes alcohol, smokes, or tobacco usage then that person possesses infertility. Being overweight is one of the responsible factors for infertility in men (Okonofua et al., 2022). Smoking tobacco like marijuana also reduces sperm production and thereby increases the risk of infertility in the male. Being Underweight is one of the reasons for infertility. Excessive use of exercise with steroids also increases the risk of infertility. The environmentis another factor that is responsible for the development of infertility. Those people are continuously exposed to heavy chemicals, toxins, radiation, X-rays and excessive temperature in the testicles can impair the synthesis of sperm or death of the sperm(Ueda et al., 2022). If a male person experiences any trauma in the testicles is the major contributing factor to male infertility.
Temperature maintenance is the main factor in the development of sperm. If the temperature is not maintained in the testicles then accordingly it causes male infertility. Long-term exposure to pollution also causes male infertility in the United Kingdom. Various lifestyle factors including nutrition, exercise, physical and psychological stress, environmental and occupational exposure, use of the abusive drug, and medication are the major contributing factors to male infertility in the United Kingdom.
Regular intake of alcohol and drugs also aids in the development of male infertility.
Classification of Azoospermia
The term “Azoospermia” is the pathological condition in which in sperms are not generated in ejaculation. This can be due to arise any obstruction in the “vas deference” which prevents the ejaculation of the sperm. This can be non-obstructive (Davalieva, et al., 2022). This may be due to impaired production of sperm in the seminiferous tubules. “Azoospermia” are categorized into three groups known as “pretesticular”, “testicular”, and “post testicular". 40% of a male are suffering from obstructive "azoospermia". Whereas 60% of male persons were diagnosed with non-obstructive “Azoospermia". It has been found that about 1% of infertile male is suffering from “Azoospermia”. “Testicular azoospermia” are due to inadequate stimulation in the genital tract for the production of sperms as a result of the lower level of testosterone hormone in the blood. “Testicular Azoospermia” is mainly due to testes being abnormal, atrophic, or may be absent to produce sperm. “Post testicular Azoospermia” refers that sperms being produced but not ejaculated in the male genital tract due to the obstruction present in the tract.
Causes of azoospermia
“The Azoospermis” may arise due to the blockage in the reproductive tract. This may also arise due to any structural defects in the ejaculatory ducts. The main obvious cause of “azoospermia” can be vasectomy in males. Vasectomy decreases the entry of sperm from the epididymis to the vas deference for ejaculation. The other reasons may be due to poor testicular development, or due to environmental toxins (Çitli et al.2022). Excessive anxiety in the male person and the increased stress level may affect the production of sperm as a result it causes the development of “Azoospermia”. Various infections may cause “Azoospermia” such as “epididymitis” and “urethritis”. Any viral infection like “viral orchitis” causes swelling in the testicles which cause the impaired synthesis of sperm. Any injury in the testicles may the reason for the "Azoospermia”. If a person suffering from cancer then he/she should undergo radiation techniques which may cause the production of sperm in the testes (Rahoui, et al.,2022). Gene is another responsible factor for "Azoospermia”. A person born with a chromosomal disorder like “Klinefelter’s syndrome” also causes Azoospermia. Any imbalance in the hormonal control of spermatogenesis also causes “Azoospermis”. Any trauma or injury in the pelvic area may arise this condition. In another sense, if there is any development of cysts in the testes may also be the reason for the development of "Azoospermia” in males. If there are any abnormal conditions like “cryptorchidism” or “post testicular” it means the testes are not descending from the abdomen which means it is absent in the scrotum. “Testicular torsion” and any changes in the temperature in the scrotum may also arise the impaired synthesis of sperm in the testes and as a consequence, there is the development of "Azoospermia”.
Reasons for non-obstructive azoospermia (NOA)
There are some other reasons for the development of non-obstructive azoospermia. Genetic and Y chromosome deletion is the most prevalent reason for the development of NOA. Y chromosome deletion causes about 10% of the azoospermia in males. As these chromosomes are responsible for the male characteristics. Any karyotype abnormality means the abnormal count of chromosomes in which there is an extra "X" chromosome in the case of males can cause the abnormal synthesis of sperm in the testes (Tang et al., 2022). Radiation such as chemotherapy, radiation therapy, and toxins such as heavy metals decrease sperm production and thereby increasing the risk of NOA. “Varicocele” means enlargement of the veins and broadening of the veins may impaired sperm production. If a person takes a testosterone supplement to treat any disease may also arise of the Azoospermia.
Male investigation and Diagnosis
A person with the problem of infertility undergoes some physical examination and medical history check and the doctor often asks a question about if there are any chronic health problems, illness, or any kind of surgery that can aid in to arise of the infertility problem. Another method Semen analysis was also done as a diagnostic measure (Huang, et al., 2022). As that could help to know the sperm count of that person. Doctors may also recommend some other diagnostic measurements such as “transrectal ultrasound”, “Scrotal ultrasound”, “Testicular biopsy”, and “Post-ejaculation urinalysis”, “Specialized sperm function tests”. Another method is the “Sperm Penetration Assay” which can be done to confirm the stability of the sperm to be fertilized.
In order to diagnose the NOA, post-ejaculatory urine should be tested for the presence of sperm. Any sperm present in the urine means there is a retrograde ejaculation of the sperm. First semen analysis can be done to test male infertility. Later on, other tests are required. Then the blood test is also done to observe the level of reproductive hormones like FSH, and LH to induce spermatogenesis. Nonobstructive infertility can be diagnosedsed with “anamnesis”.
Genetic causes and identification of nonobstructive azoospermia
30% of a male are suffering from azoospermia due to genetic reasons in which a person possess extra chromosomes instead of any “XY” chromosomes in the body as result there is the deletion of the "Y” chromosomes and the development of monogenetic defects. As a consequence, there is an impaired synthesis of sperm in the male genital tract. Genetic disorders cause morphological changes in the sperm. As a result poor, weak sperm are produced which are unable to fertilize an ovum. Any problem in the gene may also arise some cysts in the testicles as a result there is impaired synthesis of sperm. If there is any mutation in the gene of a person can alter the synthesis of sperm production there by the development of Azoospermia. Other genetic defects such as “Kallmann syndrome”, and “mild androgen insensitive syndrome” also impaired the synthesis of sperm (Malche et al., 2022). Hormonal treatment can be done for a person diagnosed with “Azoospermia”. Genes responsible for the production of sperm are also associated with the “ciliary function” “flagellar maintenance,” and “steroid receptor function”.
Conclusion
Spermatogenesis is the process of the development of sperm in the male genital tract of a male person. This process comprises a series of stages. Nowadays infertility is one of the major reasons for spermatogenesis in the UK. It has been found that various factors such as smoking, alcohol intake, use of abusive drugs, and excessive exposure to pollution are the major contributing factors to male infertility in the United Kingdom. There are some other structural defects that cause male infertility. Male infertility may result in the development of “Azoospermia”. However male infertility can be treated with hormonal treatment, surgical methods, or any use of the drug.
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