Sertoli cell as a model in male reproductive toxicology: Advantages and disadvantages

Abstract

Pressure towards population aging in the demographic pyramid is not only due to sociological/personal choices but also due to subfertility or infertility. There are several chemicals and mixtures that impair male fertility. While experimental animal models are crucial to identify compounds that affect male fertility, it is essential to use reliable in vitro models to determine cellular targets and intracellular pathways that mediate chemical toxicity in the male reproductive system. In this review, we focused on the somatic Sertoli cell (SC) that, within the testis, is a major target for hormonal signaling and provides physical and nutritional support to developing germ cells. The different outcomes possible in each type of study: in vivo versus in vitro (either in primary or immortalized cell cultures) are analyzed. Herein, we intend to clarify the unique features that render SCs as excellent candidates for a robust in vitro model to study the deleterious effects of chemicals on male reproductive health. The sensitivity of SCs to toxicants/pharmaceuticals is discussed and, based on the literature reviewed we propose the in vitro study of SC physiology as a model to disclose deleterious effects of substances to male fertility.

Exposure of male mice to two kinds of organophosphate flame retardants (OPFRs) induced oxidative stress and endocrine disruption

“…Their functions could be altered through a mechanism mediated by oxidative stress and mitochondrial dysfunction caused by endocrine disruptor (Reis et al, 2015). Thus, the results above indicated that the oral administration of TPP and TCEP for 35 days had adverse effects on the endocrine system in male mice.…”

Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?

“…This in vitro model has also been used for mechanistic studies to probe the molecular events underlying toxicant-induced Sertoli cell TJ-barrier disruption or Sertoli cell-gonocyte interactions, such as cadmium, BPA, PFOS and phthalates, which faithfully reproduce findings in vivo such as by identifying the downstream signaling MAPKs p38, ERK1/2 or JNK (Table 1) . Thus, Sertoli cells cultured in vitro is a good and reliable model to study male reproductive toxicology [58]. It must be noted that findings based on this in vitro system using rat (or mouse) Sertoli cells may not be applicable to reproductive toxicology in humans in vivo for a number of reasons.…”

4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells

“…It is now well established that the in vitro study of SC physiology is a useful model to disclose deleterious effects of toxicant exposure to male fertility and to probe the molecular mechanisms that regulate spermatogenesis (Li et al 2016;Reis et al 2015). Therefore, in the present study, we established both the SC and rat models to determine the effect of NP on the activity of autophagy in SCs and to explore its underlying mechanisms in view of the intriguing role of AMPK-mTOR signaling pathway.…”