Post Date November, 16 2024
Many cellular and molecular level changes related to spermatogenesis, maturation, emission, fertilization, etc. are unique and closely related to the fertilization ability of sperm, which is closely related to the control of male fertility regulation. Taking the development process of sperm cells as an example, we can see an overview of future research directions and strategies in male science.
1、 Formation of Golgi apparatus, lysosomes, and acrosome
Until now, people's understanding of this system in sperm cells is still extremely superficial. A series of questions related to the 6-phosphate mannose receptor and its function, spectral analysis of acidic hydrolases in the acrosome, whether the acrosome contains proteoglycans, oxygenoglycans, or sulfated glycans, whether the H+pump in the acrosome is similar to other erythrocyte cytoplasmic or lysosomal pumps, and the morphological pathway of molecules entering the developing acrosome through the Golgi apparatus of sperm cells are the most important ways to understand the function of sperm cells. Similarly, there is almost no knowledge about the detailed composition of the plasma membrane of sperm cells. For example, is there a specific antigen, and is the membrane protein fixed together with other membrane molecules through certain glycophospholipids? What is the relationship between the cytoplasmic membrane and developing structures such as mitochondrial or fibrous sheaths? These knowledge are fundamental for understanding the relationship between sperm cells and supporting cells, as well as how sperm cells develop towards sperm. An interesting question is whether this relationship involves a cell adhesion molecule that has been confirmed in other systems and is related to overall adhesion.
From a pharmacological perspective, it can be suggested that ion carriers have an effect on reproductive function, as carboxylic ion carriers such as monensin can cause infertility in rats. Cats seem to consume a large amount of monensin, but it is unclear whether the drug affects their fertility. An important suggestion is to search for drugs that can affect cell ion balance and explore their potential anti fertility effects. People are not yet clear about the cytoskeleton and nuclear layer of sperm cells, nor do they understand their relationship with sperm cell differentiation. It is impossible to design any new contraceptives until these basic questions are answered.
2、 Formation of centrioles, cilia, and flagella
The 9+2 skeleton arrangement of sperm tail flagella axoneme and microtubules is well-known, but the biochemical definition of flagella membrane proteins is not clear. It has been confirmed in other tissues that any influence on the mechanism of flagellar axonal activity can interfere with the movement of cilia, so this interference should affect the vitality of sperm. It is difficult to develop antibodies or drugs targeting flagellar motor components such as flagellar membrane proteins and flagellar axons that can be used by both men and women, and to transport antibodies or drugs to the site of action. However, the reason for interest is that membrane proteins are susceptible to interference, and such antibodies or drugs may also interfere with the interaction between sperm and eggs. The membrane protein system that should be defined also involves membrane receptors for sperm cyclophosphamide metabolism, which are related to sperm activation. The activation of sperm during ejaculation may involve membrane Mg ATPase (activated by calcium calmodulin), as sperm seem to need to pump out calcium ions to activate their vitality. Understanding the characteristics of this hypothetical pump and purifying them is crucial for designing drugs or antibodies that inhibit its activity in the future.
Interrupting the development of sperm tails will maximize sperm infertility. The haploid gametes after meiosis have transcriptional activity, which may play an important role in regulating sperm development. For example, sperm protamine (related to DNA packaging) is one of the proteins synthesized from mRNA that has been stored for many days during this stage. Further research should be conducted on other rich proteins synthesized, such as the outer layer of dense fibrin. As for the role of the neck of sperm in the formation of sperm nuclei, people have understood its ultrastructural changes, but it is not yet clear about its biochemical changes. The experimental results indicate that 20% of the synthesized sperm microtubule proteins after meiosis have amino acid compositions different from their tissues (such as the brain). This difference provides clues for people to selectively search for potential attack points for fertility regulation. The target also includes outer dense fibers and fiber sheaths.
During the process of sperm differentiation, the centriole moves to the opposite pole of the acrosome, and if it is not in place, flagella cannot be formed. How does this movement occur, involving microtubules, actin, and kinesin? Can existing centrosome/centrosome antibodies be used to interfere with this movement or drugs can be used to interfere with the cytoskeleton? The key is how to transport antibodies or drugs to newly defined membrane/flagellar axoneme/centriole proteins. Injecting is probably a pathway that should not be ignored. How to monitor antibody titers afterwards? When do I need to strengthen the injection again? The unique characteristics of the sperm neck are undoubtedly related to the centriole, which will be important for future research and development of male reproduction. However, the knowledge gap in this field is too large, and great efforts need to be made to find breakthroughs in future anti fertility measures.
3、 Cellular and molecular biology aspects of sperm cells
As a practical male contraceptive, it must:
(1) Effectively blocking one or more stages of germ cell development, thus eliminating its fertilization ability;
(2) Its effect must be reversible;
(3) The dosage, route of administration, and side effects must be accepted by the drug user and the entire society.
Potential areas for exploration include:
(1) The cell arrangement structure supporting cells and the entire seminiferous tubules is essential for the development of germ cells; Utilize the covalent binding ability of FSH analogues that can specifically and uniquely bind to FSH receptors as target specific inhibitors for supporting cells.
(2) Although there is a reversibility issue caused by damage to the seminiferous tubule barrier (causing irreversible orchitis) and severe shortage of stem cells after damage to spermatogonia, other techniques that can be used to interfere with the function of primary spermatocytes in the basal chamber can also be considered. What is the most vulnerable stage of germ cell development due to temperature sensitivity?
(3) The process of sperm entering the epididymis through the testicular network through the testicles. What is the mechanism of sperm migration process? Is it a premature release? Is there any ion or specific protein in the testicular reticulum? What is the function of its epithelium?
The maturation mechanism during epididymal transport is whether local anti androgens (local interference with androgen receptors or occupation of androgen receptors by a competitive analogue or "toxin") can be utilized to inhibit epididymal epithelial cells. Verifying the proteins synthesized by epididymal epithelial cells and how they bind to sperm is also important for understanding their function and seeking anti fertility pathways.
Future research on male contraception may involve studying the amino acid sequence of sperm surface proteins and the molecular composition of lipids, as well as their relationship with sperm motility, capacitation, hyperactivation, and sperm egg binding.
