PhD defence R.E. (Rosalieke) Wiegel

Below is a brief summary about the dissertation:

Inadequate adaptation during early pregnancy can lead to complications such as fetal growth restriction and preeclampsia, which contribute to maternal and perinatal morbidity and mortality worldwide. The activation of the renin-angiotensin-aldosterone system, which increases during follicular development, ovulation and early pregnancy, is a major regulator of blood pressure and fluid homeostasis during gestation. One of its components, prorenin is released in significant amounts from the ovaries and uteroplacental unit. During the establishment of pregnancy, the corpus luteum, a unique temporary endocrine structure of the ovary, plays a significant role as primary source of reproductive hormones before the placenta becomes sufficiently developed to supersede. Prorenin is released by the corpus luteum along with other factors like estrogen, progesterone, and relaxin, that individually or through modulation of the circulating renin-angiotensin-aldosterone system activity, might affect maternal hemodynamic adaptation to pregnancy. Prorenin, the precursor of renin, has plasma concentrations that are 10-fold higher than those of renin, and this increase to ~100-fold in follicular fluid. Given its local synthesis, it is commonly assumed that there is also an independent ovarian renin-angiotensin system, resulting in high local angiotensin (Ang) II levels. Despite prorenin's high concentrations and local synthesis in the reproductive system, its biological function remains unknown beyond being the precursor of renin.

In this thesis, we aim to investigate the impact of periconceptional ovarian endocrine health as an important determinant of early adaptation to pregnancy by studying the oocyte, preimplantation embryo, utero(placental) vascularization, fetal and placental growth and development and pregnancy outcomes, with the emphasis on the renin-angiotensinaldosterone system. The research involves studying women who conceived naturally or through assisted reproductive technology, with the goal to unravel the role of the ovary in the (patho)physiology of maternal pregnancy adaptation and associated complications. The findings of this thesis can have implications for maternal and child health throughout the life course.