There is growing concern about the considerable decline in semen quality and the increase of male reproductive disorders such as testicular cancer, hypospadias and cryptorchidism over the past decades. Male Reproductive Disorder is a multifactorial pathological condition affecting approximately 7% of the male population. Considering that ∼10% of the human genome is involved in reproduction, it stands to reason that a genetic mutation affecting male reproductive disorder could have a concurrent effect on other physiologic processes as well. The genetic landscape of male Reproductive Disorder is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2,000 genes are involved in spermatogenesis. The highest frequency of known genetic factors contributing to male Reproductive Disorder (25%) is in azoospermia, but the number of identified genetic anomalies in other semen and aetiological categories is constantly growing. Genetic screening is relevant for its diagnostic value, clinical decision making, and appropriate genetic counselling. Anomalies in sex chromosomes have major roles in severe spermatogenic impairment. Autosome-linked gene mutations are mainly involved in central hypogonadism, monomorphic teratozoospermia or asthenozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenic disturbances.
There is an emerging body of evidence suggesting that male Reproductive Disorder may be a harbinger of future health. Potential associations between Reproductive Disorder and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible links between male Reproductive Disorder and oncologic, cardiovascular, metabolic, and autoimmune diseases. Male Reproductive Disorder can be caused by a wide range of conditions, encompassing anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies.
Several hypotheses have been put forth including testicular dysgenesis syndrome, chromosomal abnormalities, damaged DNA repair mechanisms, or Y chromosome abnormalities. With the use of advance reproductive techniques, more men are bypassing a male fertility specialist who may be positioned to diagnose or counsel patients regarding these risks.
When your doctor suspects you may have Reproductive Disorder, what comes next is a careful series of tests and examinations that will confirm the diagnosis and assess the extent of the disease. Most Reproductive Disorder cases are highly treatable, but first, your care team needs to exactly what you’re dealing with. Establishing a routine schedule for Reproductive Disorder screening is the best way to detect Reproductive Disorder in its earliest stages—giving you the greatest chance of successful treatment.
In spite of clear evidence for genetic causes of Reproductive Disorder, the genetic architecture of this condition has largely remained elusive, and few variants have been confirmed as causative in male reproductive disorders, including Yq microdeletions that contribute to as much as 18% of severe oligozoospermia and non-obstructive azoospermia (NOA) cases, Klinefelter’s syndrome present in nearly 15% of men with severe spermatogenic defects and mutations in the CFTR gene responsible for 78% of cases with congenital bilateral absence of the vas deferens. However, GWAS studies are notoriously known to be limited to variants of low effect size (odds ratio <1.5) at intermediate frequency, and, historically, have only explained a small fraction of heritability of complex traits. Similar to research in other complex diseases, primary attention in male infertility has now shifted towards the low-frequency variants (minor allele frequency, MAF<5%) of large effect.
A growing body of data derived from epidemiological studies indicates an increased risk of cancer in men with spermatogenic defects. A number of shared biological processes could account for a shared etiology of male infertility and cancer, including cell survival, cell fate, and genome maintenance. While only a small fraction of genes likely to be involved in both tumorigenesis and failed spermatogenesis, they are intended to illustrate the basic cellular processes whose disruption could explain the relationship between the two conditions.
A more complete understanding of the unifying mechanisms for Reproductive Disorder and cancer will require large scale, whole genome studies in both fields. As genomic data continue to accumulate for both disease classes, increased understanding of the underlying mechanisms, shared genetic etiologies and potential risk to offspring will pave the way for germline screening for cancer and infertility susceptibility loci toward improved patient care.