Nitric Oxide and its Role During Pregnancy: From Ovulation to Delivery

Abstract

Nitric oxide (NO) is a major paracrine mediator and important regulatory agent in various female reproductive processes, such as ovulation, implantation, pregnancy maintenance, labor and delivery. Ovulation: Circulating NO-products are increased during follicle development and decreased right after ovulation. INOS-inhibition results in a 50% reduction of ovulation, an effect completely reversed by an NO. Endometrium/Implantation: NO also regulates endometrial functions such as endometrial receptivity, implantation and menstruation. NO-donors may be useful for promoting fertility, while NO-inhibitors might be used for contraception. Uterine contractility: Throughout gestation myometrial NO-production is upregulated thus contributing to achieve uterine quiescence. Close to term, NO-production decreases promoting effective contractions resulting in labor. Clinical trials have demonstrated that NO-donors are effective tocolytics. Cervical ripening: In contrast to the myometrium, NO-production in the cervix is low during gestation and becomes upregulated once pregnancy advances to term. NO-donors are effective and safe cervical ripening agents. This finding from animal studies has been confirmed by several clinical trials. Vasoreactivity: In blood vessels, NO is a potent vasodilator and platelet-aggregation-inhibitor. Lack of NO during gestation was related to the development of pregnancy-induced hypertension and preeclampsia. In conclusion, NO-donors and NOS-inhibitors may provide novel, effective, safe, and inexpensive drugs to regulate and steer various functions in female reproductive life. The benefits reach from contraception to preventing possibly lethal pregnancy complications such as preeclampsia. Introducing NO-donors as tocolytics and cervical ripening agents may contribute to a reduction of fetal and maternal perinatal morbidity and mortality.

Within-litter variation in birth weight: impact of nutritional status in the sow

“…Furthermore, arginine stimulates the AKT1-mTOR/FRAP1-RPS6K-RPS6 cell signaling pathways to increase proliferation and migration of porcine (Kong et al, 2012) and ovine (Kim et al, 2011) trophectoderm cells during peri-implantation period. The positive impact of L-arginine supplementation during the peri-implantation period of pregnancy is due in part to the production of NO, since this is crucial for embryonic development and implantation (Maul et al, 2003;Wang X.Q. et al, 2014a).…”

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

“…The importance of NO as a regulator of early developmental events has been established by studies that demonstrated that the oocyte and preimplantation embryo are exposed to NO, and oocyte maturation, preimplantation embryogenesis and implantation require NO (Biswas et al, 1998;Gagioti et al, 2000;Maul et al, 2003;Novaro et al, 1997;Purcell et al, 1999;Sengoku et al, 2001;Shukovski and Tsafriri, 1995;Telfer et al, 1995). Moreover, in vitro and in vivo studies showed that administration of either NOS inhibitors or NO donors hinders development of preimplantation embryos (i.e.…”

Intracervical Foley Catheter versus Vaginal Prostaglandins for Induction of Labor in Women with Previous One Cesarean Section-A Pilot Study

“…Cervical ripening is an active process resembling an inflammatory reaction, which involves a complex cascade of degradative enzymes accompanied by degradation and disorganization of collagen framework, increased water content, and rearrangement of extracellular matrix proteins and glycoproteins [14,15]. Among factors regulating cervical ripening (i.e, mechanical factors, estrogens, cytokines, neuro-peptides, and other inflammatory agents), prostaglandins are regarded to have a crucial role [16].…”