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 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, the 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, the 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 suggest the topics for future research.

Modulation of endometrial E-Cadherin and N-Cadherin by ovarian steroids and embryonic stimuli

“…These observations indicate that the integrity of the luminal epithelium is a determinant of the ability of the embryo to implant. In most mucosal surfaces, the integrity of the epithelium is maintained by junctional complexes which are composed of an array of proteins (Díaz-Díaz et al, 2020;Piprek et al, 2020). One key protein of the junctional complex is Epithelial-Cadherin (E-Cad) which is developmentally required for epithelial biogenesis (Gall and Frampton, 2013).…”

“…Further, the expression of E-Cad is altered in the endometrial epithelium of infertile women (Matsuzaki et al, 2010;Kakar-Bhanot et al, 2019;Sancakli Usta et al, 2020;Whitby et al, 2020) suggesting a key role of this protein in adult endometrium. Beyond its role in the biogenesis of epithelium, E-Cad also plays a role in defining the apicobasal polarity of the epithelium and is a pre-requisite for directionality during the secretory and absorptive functions for maintenance of homeostasis (Desai et al, 2009;Gall and Frampton, 2013;Schnoor, 2015;Jiang et al, 2018;Piprek et al, 2020). Interestingly, there are stage-dependent changes in apico-lateral sorting of E-Cad in the endometrium.…”

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.…”