Myo-Inositol Safety in Pregnancy: From Preimplantation Development to Newborn Animals

Abstract

Myo-inositol (myo-Ins) has a physiological role in mammalian gametogenesis and embryonic development and a positive clinical impact on human medically assisted reproduction. We have previously shown that mouse embryo exposure to myo-Ins through preimplantation development in vitro increases proliferation activity and blastocyst production, representing an improvement in culture conditions. We have herein investigated biochemical mechanisms elicited by myo-Ins in preimplantation embryos and evaluated myo-Ins effects on postimplantation/postnatal development. To this end naturally fertilized embryos were cultured in vitro to blastocyst in the presence or absence of myo-Ins and analyzed for activation of the PKB/Akt pathway, known to modulate proliferation/survival cellular processes. In parallel, blastocyst-stage embryos were transferred into pseudopregnant females and allowed to develop to term and until weaning. Results obtained provide evidence that myo-Ins induces cellular pathways involving Akt and show that (a) exposure of preimplantation embryos to myo-Ins increases the number of blastocysts available for uterine transfer and of delivered animals and (b) the developmental patterns of mice obtained from embryos cultured in the presence or absence of myo-Ins, up to three weeks of age, overlap. These data further identify myo-Ins as a possibly important supplement for human preimplantation embryo culture in assisted reproduction technology.

Maternal Inositol Status and Neural Tube Defects: A Role for the Human Yolk Sac in Embryonic Inositol Delivery?

“…As early as preimplantation stages of mammalian development there is a notable requirement for myo -inositol, with uptake increasing from the 1-cell to the blastocyst stage; myo -inositol incorporation into the phosphatidylinositol cycle promotes cell proliferation ( 16 – 19 ). Mouse embryos exposed to myo -inositol in vitro display an increase in proliferative activity and a faster cleavage rate resulting in more blastocysts ( 20 , 21 ). Hence myo -inositol transporters must be active over this period of preimplantation development to meet myo -inositol demand if this cannot be met by endogenous production.…”

Inositol and antioxidant supplementation: Safety and efficacy in pregnancy

“…In mouse models, the preimplantation embryo exposure to Myo (10mM) resulted in absence of early toxic effects, as suggested by normal prenatal and short‐term postnatal development, and in a significant increase in the overall rate of the live births obtained, as compared with embryos cultured in absence of Myo …”

High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries

“…In fact, MyoIns concentration in the mammalian female reproductive tracts is substantially higher than in plasma [ 46 ] and a deficiency of MyoIns is known to impair oocyte and embryo quality [ 47 ]. On the contrary, supplementation of MyoIns to in vitro cultured mouse oocytes and embryos enhances their ability to complete preimplantation development [ 47 , 48 ] and to develop to term normally [ 49 ]. MyoIns (such as inositol trisphosphate, IP 3 ) is one of the second messengers of FSH in the ovary [ 50 ], relevant for granulosa cell function and folliculogenesis.…”