The Central Role of Cadherins in Gonad Development, Reproduction, and Fertility

Abstract

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but they also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood–testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes and facilitate the capacitation of sperm in the female reproductive tract and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins; however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and we suggest topics for future research.

The “Hitchhiker’s Guide to the Galaxy” of Endothelial Dysfunction Markers in Human Fertility

“…Intercellular junctions are mainly formed by cadherins/catenins cell adhesion protein complexes and integrins, which connect proteins of the extracellular matrix to the intracellular cytoskeleton [ 171 ]. The main role of this barrier is the control of those molecules that could reach the intraluminal site and, in turn, the spermatogenic cells, limiting interferences in sperm maturation [ 170 , 172 ]. Indeed, there is evidence supporting that several chemotherapy agents induce spermatogonia differentiation arrest and the blockade of spermatocyte meiosis.…”

The germline-specific region of the sea lamprey genome plays a key role in spermatogenesis

“…Further, several of the gene families known to be essential for spermatogenesis are highly duplicated. For example, cadherins (cadh) are responsible for maintaining the integrity of testis structure 39 ; cyclins (ccnb) are essential for cell progression during distinct phases of the male spermatogenesis pathway 40 ; RNA binding proteins (rbm) play diverse and important roles in spermatogenesis including testis-specific splicing 41 and the absence of rbm46 (present in 16 copies in the sea lamprey GSR) is associated with male infertility in mice 42 . Other important genes e.g., sox9 and cbx2 which play roles in stabilizing the male differentiation pathway, are present in the somatic genome of sea lamprey.…”

Transcriptomic Profile of New Gene Markers Encoding Proteins Responsible for Structure of Porcine Ovarian Granulosa Cells

“…It is important to consider the role of cell signaling on reproductive efficiency, including via the ECM, cadherins, and integrins [ 22 , 23 , 24 , 25 , 26 ]. Cadherins and integrins are among the transmembrane proteins that are closely involved in intercellular signaling.…”

“…The action of both groups of proteins is through their effect on F-actin [ 26 ]. Several groups are distinguished among the cadherins: N-cadherin (neural cadherin), P-cadherin (placental cadherin), R-cadherin (retinal cadherin), VE-cadherin (vascular endothelial cadherin), and the E-cadherin (epithelial cadherin) found in the epithelium of various tissues and have been implicated in the function of the reproductive system [ 22 ]. More than two decades ago, the expression of these transmembrane proteins in porcine GCs was described and linked to the development of ovarian follicles by maintaining the structural integrity of the follicle through E-cadherin [ 27 ].…”