A Comparative Analysis of the Altered Levels of Human Seminal Plasma Constituents as Contributing Factors in Different Types of Male Infertility

Abstract

(1) Background: The relationships between the biochemical and immunological components in seminal plasma and their physiological effects on male reproductive system have been underreported. In this study, we evaluated the potential of several seminal plasma biochemical and immunological markers in the pathophysiological developments of the infertile male patients. The study was designed to identify and assess different markers that may be associated with semen functions in different types of male infertility. (2) Methods: A total of 50 infertile male patients who underwent checkup for fertility assessment and 50 fertile controls were included in this study. The complete medical history of each recruited participant was reviewed. The infertile sub-groups (non-obstructive azoospermia (NOA), asthenozoospermia (AS), normozoospermic infertile (NI), and oligozoospermia (OZ)) were characterized based on sperm motility and concentration, while NI patients were included after a thorough check up of their female partners as well. We investigated each sample for 21 different analytes, enzymes, trace elements, and immunological markers to find crucial markers posing as contributing factors to a specific type of male infertility. (3) Results: The levels of 15 out of 21 markers, assayed from the seminal plasma of infertile males, were significantly altered in comparison to fertile controls (p < 0.05). For the first time, microprotein levels were also analyzed. The presence of monocytes, lymphocytes, and granulocytes was limited to semen from NOA patients, while a significant increase in the level of platelets was observed in AS. Hierarchical clustering and ROC-AUC analysis identified the three most significant markers (zinc, LDH, and TG) for the healthy control group and asthenozoospermic group (AUC, of 0.92 and 0.81, respectively). (4) Conclusions: The altered levels of biochemical and immunological markers in seminal plasma might be associated with the different male infertility profiles and could be required for the sperm metabolism and maintenance. However, a larger sample size and follow up analysis is required for establishing the hypothesized panel of markers as biomarkers at clinical stage.

Integration of omics studies indicates that species-dependent molecular mechanisms govern male fertility

“…In depth omics studies have recently been carried out in human and animal spermatozoa to provide a better understanding of male fertility at the genes [2][3][4][5], transcript [6][7][8], protein [9][10][11][12][13][14], and metabolite levels [6,11,[15][16][17][18]. Although these huge fertility-related omics datasets can offer prospective sources for discovering male fertility biomarkers which contribute to assess male fertility potential or sperm dysfunctions, these studies invariably contain information that is unrelated to male fertility status.…”

“…Comprehensive and comparative omics studies have recently been conducted in animals and humans to provide a better understanding of the complex multifactorial processes linked to male fertility at the gene [ 2 – 5 ], transcript [ 6 – 8 ], protein [ 9 – 14 ], and metabolite levels [ 6 , 15 – 18 ]. The development of new molecular methodologies to determine male fertility potential or sperm dysfunction has been facilitated by the accumulation of massive fertility-related omics datasets that serve as promising resources for identifying biomarkers of male fertility [ 10 , 19 ].…”

Understanding seminal plasma in male infertility: emerging markers and their implications

“…62,134,135 Also, our own study investigating the effects of seminal plasma components on male reproductive health using atomic between zinc levels and sperm motility. 136 These studies necessitate further exploration to unravel Zn's exact contributions within the complex process of spermatogenesis.…”

“…107.300 ± 2.103 mmol/L) as compared to fertile controls were also observed when measured using an electrolyte analyser. 136 These levels potentially hint at the presence of an underlying defect perturbing the interplay of these complex ion transport mechanisms and need to be further addressed. Thus, investigating the potential interplay between trace elements along with proteins and metabolites could uncover synergistic or antagonistic effects that contribute to male reproductive health outcomes.…”

“…These limitations associated with imaging techniques create a unique opportunity for the development of molecular biomarker-based tests, which could enable prompt decision-making at reduced cost and increased accessibility. Moreover, our extensive interactions with infertile male patients during our research on altered levels of seminal plasma constituents 136 have strongly indicated that utilising seminal plasma as a means of analysing biomarkers would be a more preferable approach as compared to invasive techniques. This offers several advantages, including avoiding the direct access to the systemic circulation as invasive procedures being painful and uncomfortable often breach organ barriers and pose the risk of introducing pathogens into the body, leading to infection.…”