Infertility is a medical condition in which a clinical pregnancy cannot be achieved following twelve months of regular, unprotected sexual activity. Worldwide, one out of six couples of childbearing age experience infertility (Matzuk and Lamb, 2008, Carson and Kallen, 2021). The process of getting pregnant involves many important processes, such as follicular development, fertilization, implantation, and beyond. Thus, uterine fibroids, endometrial polyps, endometriosis (Saunders and Horne, 2021), polycystic ovarian syndrome, early ovarian insufficiency (Touraine, 2020), and polycystic ovary syndrome (Hoeger et al., 2021) are all potential contributors to female infertility. Physical and psychological stress, the enormous financial burden of infertility therapy, an unsatisfactory success rate, and other difficulties remain unresolved despite the development of an evidence-based, cost-effective, and safer reproductive treatment in recent years (Öztürk et al., 2021). There is an immediate need to improve our knowledge of the molecular mechanisms underlying infertility-related illnesses and to develop more effective therapies in a timely manner.

There has been a recent increase in research into the intricate roles that intercellular communication plays in regulating a wide range of physiological processes, such as cell proliferation, differentiation, gametogenesis, embryogenesis, and development. Specifically, the field's research efforts have been redirected due to the discovery of extracellular vesicles (EVs) as new mediators of intercellular communication. In the past, there were three main ways in which cells could communicate with one another: directly, through membrane-bound signaling molecules (receptors) or gap junctions; indirectly, through secreted soluble molecules (paracrine signals), like cytokines and chemokines; and finally, through hormones, which are secreted into the bloodstream. The presence of EVs has only recently been discovered; these vesicles are secreted into the extracellular space by cells and can transport lipids, proteins, and RNAs between cells in both local and distant contexts (Zhang et al., 2009, Raposo and Stoorvogel, 2013). Under normal and pathological conditions, a variety of cell types release EVs. The cargo carried by EVs have the potential to be important in many areas of biology, such as reproduction, health and disease biomarkers, and therapeutic intervention targets (Gould and Raposo, 2013). Various biological processes require EVs, a diverse set of membrane-bound structures that play key roles in intercellular communication. Depending on their size and biogenesis, they can be categorized into multiple subgroups. Several reproductive tissues have been found to contain EVs, including the testis, epididymis, uterus, ovarian follicles, and oviductal fluid (Table 1). There is mounting evidence that EVs play a pivotal role in intercellular communication throughout organs and tissues by enabling recipient cells to undergo functional changes. Sperm rely on extracellular vesicles (epididymsomes) that originate in the epididymis and measure 50–250 nm for their passage through the epididymis. It was found that epididymis-extracellular vesicles could regulate transcription and translation within these cells, as well as transfer proteins to surrounding epithelial cells and sperm (James et al., 2020). The transfer of microRNAs from epididymal epithelial cells to spermatozoa appears to be another mechanism by which microRNAs regulate sperm maturation (Wu et al., 2020). Additionally, multiple studies have shown that the content of epididymis-extracellular vesicles, which is influenced by the metabolic contents of the parent, impacts the health of the offspring (James et al., 2020). Further evidence suggests that sperm can be bound and the acrosome reaction can be delayed in mice by using extracellular vesicles sourced from the vaginal, uterine, and fallopian tube fluids (Dong et al., 2021). In addition, the fact that these encapsulated protein cargos and extracellular vesicles have been discovered in the human female reproductive tract implies that these vesicles play a crucial role in supporting sperm (Zhou et al., 2019, Nixon et al., 2019).

Research is currently focused on finding ways to use endometrial exosomes for clinical purposes (Gurung et al., 2020). Because their contents are protected by biological membranes, extracellular vesicles are easy to manipulate. Electroporation and transfection allow for the loading of EVs with small molecules, proteins, RNA, anti-inflammatory chemicals, anti-cancer agents, miRNA, mRNA, proteins, and growth factors (El Andaloussi et al., 2013, Yang et al., 2015). There are two ways to load EVs: endogenously and exogenously. The endogenous approach involves loading parent cells with therapeutics, then producing and releasing loaded EVs (Pascucci et al., 2014). Isolated EVs undergo incubation to incorporate therapeutic agents in the exogenous method (Tian et al., 2014, Yang et al., 2014). Depending on the intended therapeutic action and tissues to be targeted, extracellular vesicles can be administered via various routes such as intravenous, subcutaneous, intraperitoneal, oral, and intranasal (Burnouf et al., 2019). The intravaginal route was used to administer EVs in the study by Lange-Consiglio et al (Lange-Consiglio et al., 2020). Various factors, including EV size, surface markers, and isolation methods, influence the biodistribution and targeting potential of EVs.