Nitric Oxide in Oocyte Maturation, Ovulation, Fertilization, Cleavage and Implantation: A little dabll do ya

Abstract

Nitric oxide synthases, the enzymes that generate NO gas, may be involved in reproduction and development of multicellular organisms at many levels and thus provide important targets for design of drugs to intervene in reproductive processes. This review focuses on the role of nitric oxide in key events of reproduction including gamete activation, fertilization, early cell divisions and implantation. A general trend highlighted by the studies reviewed is that NO plays a biphasic role in reproduction. That is, a narrow range of NO concentrations, usually low, will stimulate or enhance these early events in reproduction, but either a lack of NO or too much NO has negative consequences. One of the shortcomings of the field currently is the lack of molecular detail concerning the mechanism of NO action. This has been due in part to lack of technology for effective detection of NO and its molecular targets. A few targets of NO have been indirectly implicated and advances in this area of research will provide substrates for development of drugs to control reproductive function. Work from both invertebrate and vertebrate model systems is presented and implications for control of reproductive physiology discussed. Ubiquity of NO signaling in animals may mean that effective control of reproduction must target mediators of NO action and not NOS enzymes themselves.

Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model

“…Later studies with Nos2-and Nos3-knockout mice showed that disruption of NOS2 had no effect on ovulation rate in superovulated prepubertal females; on the other hand, NOS3 deficiency had a significant negative effect (Hefler & Gregg 2002). Our results reinforce these studies, with the added value of being performed in non-stimulated cycles in mature females (a more physiological approach, since we cannot discard interactions between NO, NOS, and exogenous gonadotropins as indicated by Thaler & Epel (2003)). Current data, hence, support the hypothesis of Gregg (2003) about the role of Nos3 as an important modulator of ovulatory efficiency in mouse.…”

“…The effects of NOS3 deficiencies in ovulation may be mediated by changes in follicle development (Jablonka-Shariff et al 1999, Tempfer et al 2000, in the preovulatory LH surge (McCann et al 2003), and/or the ovulatory process by itself (Thaler & Epel 2003). Thaler & Epel (2003), revising many previous studies, suggest a model in which the preovulatory LH surge induces follicle cells to activate NOS; NOS induces production of NO, which stimulates synthesis of prostaglandins PGE 2 and PGF 2a and, thus, ovulation.…”

“…The isoform NOS3 is involved in female reproductive function (Maul et al 2003, Thaler & Epel 2003. Studies on the effects from the lack of NOS3 have been afforded by using Nos3-knockout mice, a strain showing elevated blood pressure, decreased heart rate, and premature death in males but not in females; so the model is widely used for cardiovascular research (http:// jaxmice.jax.org/strain/002684.html).…”

“…Several studies have emphasized the role of NO and NOS, and specifically NOS3, in processes of ovulation, fertilization, implantation, and early embryo development (Gouge et al 1998, Purcell et al 1999, Gagioti et al 2000, Maul et al 2003, Thaler & Epel 2003.…”

Mitochondrial Activation and Nitric Oxide (NO) Release at Fertilization in Echinoderm Eggs

“…Furthermore, simultaneous measurements of [Ca 2+ ] i and ΔΨ m revealed mitochondrial activation took place slightly earlier than ΔNO, suggesting that mitochondria may be responsible for ΔNO. ΔNO has generally been considered to be produced by cytosolic NO synthase (NOS) (Thaler and Epel 2003 ). Our data suggest that mitochondria may have their own separate generation system of NO such as mitochondrial NOS, mtNOS (Finocchietto et al 2009 ).…”