Reactive Species Interactome Alterations in Oocyte Donation Pregnancies in the Absence and Presence of Pre-Eclampsia.

Manon Bos,Mirthe H Schoots,Laurie C Lau,Marie-Louise P Van Der Hoorn,Andreas Pasch,Bernadette O Fernandez,Sanne J Gordijn,Martin Feelisch,Harry Van Goor,Monika Mikus-Lelinska,Michael Eikmans

doi:10.3390/ijms20051150

Abstract

In pregnancy, maternal physiology is subject to considerable adaptations, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus. In an oocyte donation pregnancy, the fetus is fully allogeneic towards the mother, since it carries both oocyte donor antigens and paternal antigens. Therefore, oocyte donation pregnancies result in an immunologically challenging pregnancy, which is reflected by a higher-than-normal risk to develop pre-eclampsia. Based on the allogeneic conditions in oocyte donation pregnancies, we hypothesized that this situation may translate into alterations in concentration of stable readouts of constituents of the reactive species interactome (RSI) compared to normal pregnancies, especially serum free thiols, nitric oxide (NO) and hydrogen sulfide (H2S) related metabolites. Indeed, total free thiol levels and nitrite (NO2−) concentrations were significantly lower whereas protein-bound NO and sulfate (SO42−) concentrations were significantly higher in both oocyte donation and naturally conceived pregnancies complicated by pre-eclampsia. The increased concentrations of nitrite observed in uncomplicated oocyte donation pregnancies suggest that endothelial NO production is compensatorily enhanced to lower vascular tone. More research is warranted on the role of the RSI and bioenergetic status in uncomplicated oocyte donation pregnancies and oocyte donation pregnancies complicated by pre-eclampsia.

Highlights

In pregnancy, maternal physiology is subject to considerable adaptation, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus [1,2,3,4]
Seventy-nine pregnant women were included in this case-control study; women experienced an uncomplicated naturally conceived pregnancy, women had a naturally conceived pregnancy complicated by pre-eclampsia, 27 women experienced an uncomplicated oocyte donation pregnancy, and 5 women had an oocyte donation pregnancy complicated by pre-eclampsia
Maternal age was significantly lower in uncomplicated naturally conceived pregnancies and naturally conceived pregnancies complicated by pre-eclampsia compared to uncomplicated oocyte donation pregnancies and oocyte donation pregnancies complicated by pre-eclampsia

Summary

Introduction

Maternal physiology is subject to considerable adaptation, including alterations in cardiovascular and metabolic function as well as development of immunological tolerance towards the fetus [1,2,3,4]. In a naturally conceived pregnancy, the fetus can be considered semi-allogeneic since it carries both paternal and maternal antigens [5]. Due to the enhanced allogeneic nature of oocyte donation, these pregnancies presumably need more or different maternal immune adaptations, compared to naturally conceived pregnancies [5,13,14,15]. The increased adaptive load on the immune system between naturally conceived and oocyte donation pregnancies may explain why the latter are more often accompanied by immune-disturbance related obstetrical complications, such as pregnancy induced hypertension and pre-eclampsia [13,15,16]. Oocyte donation pregnancies more often coincide with other risk factors for pregnancy complications, such as the self-evident need for artificial reproductive techniques, advanced maternal age, primiparity, cause of infertility, and multiple gestations [17,18,19,20,21]. Several studies have shown that the allogeneic nature of oocyte donation itself is an independent risk factor for pre-eclampsia [16,22,23,24,25,26]

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Results

Conclusion