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Mechanobiology in the Reproductive Tract
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Julie Anne MacDonald, Dori C. Woods
An extremely rich field of research surrounds the study of the mechanisms by which sperm travel through the female reproductive tract to fertilize an egg. Sperm are nondividing mature male germ cells, which differentiate from spermatogonial stem cells through meiotic division throughout adulthood in the male gonad. A single sperm cell, or spermatozoa, is composed of three morphological regions: a head containing the genetic material, a midpiece housing energy-producing mitochondria, and a flagellum for locomotion. This morphology allows each spermatozoa to generate forward thrust and swim through the fluid-filled portions of the female reproductive tract in order to encounter an oocyte, or female germ cell. A single ejaculation of semen introduces millions of sperm into the anterior portion of the vaginal canal. Following coitus, sperm are presented with a veritable obstacle course en route to potentially fertilize an oocyte. In order to complete fertilization, a spermatozoa must be primarily capable of surviving the physical stresses incurred by ejaculation, followed by a series of subsequent chemical stresses, including oxidative damage and pH stress caused by the acidity of vaginal fluid. In addition, because sperm are allogenic to the female, they are subject to a phagocytic immune response from invading leukocytes within the vagina, cervix, and uterus. At several points along the female reproductive tract, motile sperm are additionally met by physical barriers, such as viscous cervical mucus and the narrow uterotubal junction, at which point only actively swimming sperm are competent to continue along their route. While these various obstacles may seem daunting in and of themselves (reviewed in detail in Suarez and Pacey 2006), the ability to navigate the female reproductive tract presents perhaps the largest barrier for fertilization. Unlike most terminally differentiated cells, sperm are tasked with completing a long and treacherous journey, without the aid of any maps or road signs along the way (Figure 22.1). The few spermatozoa that survive the insemination process must be capable of reacting to the microenvironment of the female reproductive tract to navigate from the anterior vaginal canal to ultimately reach an ovulated cumulus-oocyte complex within the fertilization site, typically within the ampulla of the oviduct, or Fallopian tube. Understanding this biological feat has been the goal for numerous studies over the past decades, and here we will discuss the two most classical examples: thermotaxis and chemotaxis, with a more in-depth evaluation of the mechanically relevant rheotaxis.
A male germ cell assay and supporting somatic cells: its application for the detection of phase specificity of genotoxins in vitro
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Khaled Habas, Martin H. Brinkworth, Diana Anderson
Endogenous and exogenous chemicals, other physical and biological agents affect the genome of spermatozoa. DNA integrity of germ cells is essential for making normal motile spermatozoa (de Rooij and Russell 2000; Simhadri et al. 2014). The genomic integrity of the spermatozoa is maintained and protected by DNA repair mechanisms. These include nucleotide excision repair, base DNA mismatch repair, excision repair, double strand break repair, and post-replication repair. Failure in these mechanisms might lead to arrest of spermatogenesis or abnormal recombination, resulting in male infertility (Gunes, Al-Sadaan, and Agarwal 2015). Infertility is a condition of the reproductive system where genetic factors and environmental causes may also be involved. Although some specific mutations were identified, other factors related to sperm defects remain unidentified (Venkatesh, Suresh, and Tsutsumi 2014). Spermatogonial stem cells (SSCs) are responsible for the protection of spermatogenesis throughout male adult reproductive life. Moreover, SSCs require accurate expression of genes for the monitoring and regulation of germinal mitosis, meiosis, and apoptosis and maintenance of genomic integrity in spermatogenesis. Male germ cells need to be protected against DNA damage and mutations to maintain reproduction and species survival. Maintenance of genetic stability requires both extremely precise DNA replication processes and mechanisms for the removal of a variety of DNA damage. Damage in male germ cell as key morphological events is an indicator after administration of genotoxic chemicals (Vidal and Whitney 2014). As a consequence of exposure to genotoxic chemotherapy drugs, histopathological changes occur in the testis (Meistrich 1986). These alterations are reliant upon chemotheraptic drugs used and cell types being exposed. In the mammalian testis, different target cells identified for chemotherapy agents are germ cells (spermatogonia, spermatocytes, and spermatids) and somatic cells (Leydig and Sertoli cells) (Habas, Anderson, and Brinkworth 2016). Numerous studies in animals demonstrated that phase specificities in male germ cells selectively may be targeted by specific reproductive cytotoxic agents both in vivo and in vitro (Anderson et al. 1981; Habas, Brinkworth, and Anderson 2017c) Table 1.