Female Germ Cell Development, Functioning and Associated Adversities under Unfavorable Circumstances

Abstract

In the present era, infertility is one of the major issues which restricts many couples to have their own children. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders, etc., may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. Here in this review, various aspects of gametogenesis especially female gametes and relevant factors causing functional impairment have been thoroughly discussed.

Keywords: cancer; differentiation; gametogenesis; oocytes; pathways; signaling; stem cells; tumor.

Figure 1

Diagrammatical outflow of the PGC development and specification in mice. Oocyte and sperm after getting fertilized produces zygote. While undergoing further cell divisions, zygote attain blastocyst stage at around embryonic development day 3.5 (~E3.5) having an outer trophoblast cell monolayer and pluripotent inner cell mass (ICM) which is further separated into epiblast and primitive endoderm. Implantation of the blastocyst with the uterine wall takes place at ~E4.5. Further developmental stages are comprised of extraembryonic ectoderm (ExE) development from trophoectoderm and visceral endoderm (VE) from primitive endoderm. Furthermore, Wnt3 is secreted by both of the posterior epiblast and VE and BMP4 & BMP8b secreted by ExE. Wnt3 and BMPs secretions finally assists in production of a few primordial germ cells (PGCs) from proximal epiblast and finally PGC specification takes place.

Figure 2

Diagrammatical outflow of the PGC migration. PGCs undergo a series of events before reaching gonadal ridges and finally sex specification. They are identified as a few precursor cells at the base of allantois and specified under the effect of molecular cues associated with Wnt3 and BMP pathways. After passing through a number of stages, PGCs finally enter genital ridges and specified as male and female gametes.

Figure 3

Diagrammatical representation of factors affecting germ cell development and their functionality. All germ cell developmental stages are affected by a number of factors including mutations, chromosomal abnormalities, improper lifestyles, epigenetic dysregulations, environmental toxicants etc. Which ultimately leads to functional impairment followed by disease development. Abbreviation- Pb: Lead; Cd: Cadmium; Hg: Mercury; DNMT: DNA methyltransferase).