Mammalian Oocytes Locally Remodel Follicular Architecture to Provide the Foundation for Germline-Soma Communication

Abstract

Germ cells develop in a microenvironment created by the somatic cells of the gonad [1-3]. Although in males, the germ and somatic support cells lie in direct contact, in females, a thick extracellular coat surrounds the oocyte, physically separating it from the somatic follicle cells [4]. To bypass this barrier to communication, narrow cytoplasmic extensions of the follicle cells traverse the extracellular coat to reach the oocyte plasma membrane [5-9]. These delicate structures provide the sole platform for the contact-mediated communication between the oocyte and its follicular environment that is indispensable for production of a fertilizable egg [8, 10-15]. Identifying the mechanisms underlying their formation should uncover conserved regulators of fertility. We show here in mice that these structures, termed transzonal projections (TZPs), are specialized filopodia whose number amplifies enormously as oocytes grow, enabling increased germ-soma communication. By creating chimeric complexes of genetically tagged oocytes and follicle cells, we demonstrate that follicle cells elaborate new TZPs that push through the extracellular coat to reach the oocyte surface. We further show that growth-differentiation factor 9, produced by the oocyte, drives the formation of new TZPs, uncovering a key yet unanticipated role for the germ cell in building these essential bridges of communication. Moreover, TZP number and germline-soma communication are strikingly reduced in reproductively aged females. Thus, the growing oocyte locally remodels follicular architecture to ensure that its developmental needs are met, and an inability of somatic follicle cells to respond appropriately to oocyte-derived cues may contribute to human infertility.

Three-dimensional organization of transzonal projections and other cytoplasmic extensions in mouse ovarian follicles

“…One question is whether the TZP dynamics is induced or constitutive. In their recent study, El-Hayek et al (2018) present evidence that oocyte-derived factors induce the formation of TZPs. When the oocyte is removed from a granulosa-oocyte complex (GOC), the mRNA levels for general components of filopodia ( Damml , Fscnl , and Myo10 ) are drastically reduced in the remaining granulosa cells.…”

“…Although TZPs have been known for many years, their dynamics have not yet been characterized. A recent study has focused on this issue using a reconstituted system (El-Hayek et al, 2018). When cumulus cells that have been stripped from their innate oocyte are reaggregated with a donor oocyte, they make new TZPs, which form junctions with the oocyte.…”

“…Our observations are consistent with persistent growth and perhaps retraction of TZPs in intact follicles at a stage when the cumulus cells are already connected to the oocyte by TZPs. All TZPs contain actin but only a small minority contain microtubules (El-Hayek et al, 2018). We suggest that the free-ended TZPs contain only actin and that microtubules grow into them if they connect to the oocyte.…”

Testicular somatic cells in the stony coral Euphyllia ancora express an endogenous green fluorescent protein

“…In a variety of organisms, the adult testes and ovaries contain several specialized somatic cell types that possess the ability to support the survival, proliferation, differentiation, and development of germ cells (El‐Hayek, Yang, Abbassi, FitzHarris, & Clarke, ; Griswold, ; Osada, Harata, Kishida, & Kijima, ; Xie & Spradling, ; Young & McNeilly, ). However, in corals and even throughout the Cnidaria phylum, information regarding these cells is largely limited.…”

“…survival, proliferation, differentiation, and development of germ cells (El-Hayek, Yang, Abbassi, FitzHarris, & Clarke, 2018;Griswold, 1998;Osada, Harata, Kishida, & Kijima, 2004;Xie & Spradling, 2000;Young & McNeilly, 2010). However, in corals and even throughout the Cnidaria phylum, information regarding these cells is largely limited.…”