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Potential influence of the corpus luteum on circulating reproductive and volume regulatory hormones, angiogenic and immunoregulatory factors in pregnant women.

ABSTRACT: Cardiovascular function is impaired and preeclampsia risk elevated in women conceiving by in vitro fertilization (IVF) in the absence of a corpus luteum (CL). Here, we report the serial evaluation of hormones and other circulating factors in women who conceived with (or without) IVF. After a prepregnancy baseline, the study participants (n = 19-24/cohort) were evaluated six times during pregnancy and once postpartum (~1.6 yr). IVF pregnancies were stratified by protocol and CL number, i.e., ovarian stimulation (>1 CL) or hypothalamic-pituitary suppression (0 CL) versus spontaneous conceptions (1 CL). Results include the following: 1) relaxin was undetectable throughout pregnancy (including late gestation) in the 0 CL cohort, but markedly elevated in ~50% of women in the >1 CL cohort; 2) progesterone, plasma renin activity, and aldosterone transiently surged at 5-6 gestational weeks in the >1 CL group; 3) soluble vascular endothelial growth factor-1 (sFLT-1) abruptly increased between 5-6 and 7-9 gestational weeks in all three participant cohorts, producing a marked elevation in sFLT-1/PLGF (placental growth factor) ratio exceeding any other time point during pregnancy; 4) sFLT-1 was higher throughout most of gestation in both IVF cohorts with or without abnormal obstetrical outcomes; 5) during pregnancy, C-reactive protein (CRP) increased in 0 and 1 CL, but not >1 CL cohorts; and 6) plasma protein, but not hemoglobin, was lower in the >1 CL group throughout gestation. The findings highlight that, compared with spontaneously conceived pregnancy, the maternal milieu of IVF pregnancy is not physiologic, and the specific perturbations vary according to IVF protocol and CL status.

SUBMITTER: Conrad KP

PROVIDER: S-EPMC6842916 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Potential influence of the corpus luteum on circulating reproductive and volume regulatory hormones, angiogenic and immunoregulatory factors in pregnant women.

Conrad Kirk P KP Graham Georgia M GM Chi Yueh-Yun YY Zhai Xiaoman X Li Minjie M Williams R Stan RS Rhoton-Vlasak Alice A Segal Mark S MS Wood Charles E CE Keller-Wood Maureen M

American journal of physiology. Endocrinology and metabolism 20190813 4

Cardiovascular function is impaired and preeclampsia risk elevated in women conceiving by in vitro fertilization (IVF) in the absence of a corpus luteum (CL). Here, we report the serial evaluation of hormones and other circulating factors in women who conceived with (or without) IVF. After a prepregnancy baseline, the study participants (<i>n</i> = 19-24/cohort) were evaluated six times during pregnancy and once postpartum (~1.6 yr). IVF pregnancies were stratified by protocol and CL number, i.e ...[more]

PMID: 31408378

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Project description:UnlabelledObesity and malnutrition are associated with decreased fecundity in women. Impaired reproductive capacity in obese women is often attributed to anovulation. However, obese women with ovulatory cycles also have reduced fertility, but the etiology of their impaired reproduction is only partially understood. Accumulating evidence suggests that obesity directly impairs oocyte and embryo quality as well as endometrial receptivity. In obese women, urinary progesterone metabolite excretion is decreased, but in excess of what can be explained by suppressed gonadotropin secretion, suggesting that apart from its central effect obesity may directly affect progesterone (P4) production. These observations have led to the novel hypothesis that obesity directly affects corpus luteum (CL) function. Similarly, we hypothesize that weight loss may contribute to luteal dysfunction. Here, we propose a non-human primate model, the vervet monkey, to examine the effect of weight gain and loss on menstrual cycle parameters and CL gene expression. In this model, weight gain and loss did not significantly alter menstrual cyclicity; however, both induced alterations in the CL transcriptome. In the weight gain monkey, we observed that impaired mid-luteal P4 secretion was associated with downregulation of steroidogenic pathways in CL. Collectively, these preliminary findings support our hypothesis that weight gain and loss may contribute to CL dysfunction. The vervet model described and preliminary observations provide a basis for a larger study to address this important question. Understanding the mechanisms by which weight gain and loss contribute to reproductive dysfunction can assist in the development of targeted treatments to enhance women's reproductive capability when it is desired.AbbreviationsCL: corpus luteum; P4: progesterone; E2: estradiol; PDG: pregnanediol 3-glucoronide; LH: luteinizing hormone; FSH: follicle-stimulating hormone; GnRH: gonadotropin releasing hormone; BMI: body mass index; qrtPCR: quantitative real-time PCR; PGR: progesterone receptor; ART: assisted reproductive technology; IVF: in vitro fertilization; HPO: hypothalamic-pituitary-ovarian axis; MMPs: matrix metalloproteinases Gene symbols: LH receptor (LHGCR); cholesterol side-chain cleavage enzyme (CYP11A1); 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2); steroidogenic acute regulatory protein (STAR); LDL receptor (LDLR); scavenger receptor B1 (SCARB1); ATP-binding cassette sub-family A member 1 (ABCA1); ATP-binding cassette sub-family G member 1 (ABCG1); apolipoprotein A (APOA1); 24 dehydrocholesterol reductase (DHCR24); 3-hydroxy-3-methylglytaryl-CoA reductase (HMGCR); vascular endothelial growth factor A (VEGFA); vascular endothelial growth factor C (VEGFC); vascular endothelial growth factor receptor 1 (VEGFR1); and TIMP metallopeptidase inhibitor 1 (TIMP1); amphiregulin (AREG); epiregulin (EREG); CCAAT/enhancer binding protein alpha (CEBPBA); cAMP responsive element binding protein 3-like 1 (CREB3L1); ADAM metallopeptidase with thrombospodin type 1 motif 1 (ADAMTS1); matrix metallopeptidase 9 (MMP9); cytochrome b-245 beta polypeptide (CYBB or NOX2); NADH oxidase (NCF2 or NOXA2); Fc fragment of IgG receptor IIb (FCGR2B); Fc fragment of IgG receptor IIb (FCGR2C); ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1); RAB27A member RAS oncofamily (RAB27A); hydroxyprostaglandin dehydrogenase (HPGD); prostaglandin-endoperoxidase synthase 1 (PTGS1); integrin B2 (ITGB2); leukotriene A4 hydrolase (LTA4H); radixin (RDX); ezrin (EZR); nuclear receptor subfamily 5 group A member 2 (NR5A2).

Project description:BackgroundDespite significant advances in our understanding of the pathophysiology of preeclampsia (PE), there are still many unknowns and controversies in the field. Women undergoing frozen-thawed embryo transfer (FET) to a hormonally prepared endometrium have been found to have an unexpected increased risk of PE compared to women who receive embryos in a natural FET cycle. The differences in risk have been hypothesized to be related to the absence or presence of a functioning corpus luteum (CL).Objective and rationaleTo evaluate the literature on secretory products of the CL that could be essential for a healthy pregnancy and could reduce the risk of PE in the setting of FET.Search methodsFor this review, pertinent studies were searched in PubMed/Medline (updated June 2020) using common keywords applied in the field of assisted reproductive technologies, CL physiology and preeclampsia. We also screened the complete list of references in recent publications in English (both animal and human studies) on the topics investigated. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized.OutcomesThe CL is a major source of multiple factors regulating reproduction. Progesterone, estradiol, relaxin and vasoactive and angiogenic substances produced by the CL have important roles in regulating its functional lifespan and are also secreted into the circulation to act remotely during early stages of pregnancy. Beyond the known actions of progesterone and estradiol on the uterus in early pregnancy, their metabolites have angiogenic properties that may optimize implantation and placentation. Serum levels of relaxin are almost undetectable in pregnant women without a CL, which precludes some maternal cardiovascular and renal adaptations to early pregnancy. We suggest that an imbalance in steroid hormones and their metabolites and polypeptides influencing early physiologic processes such as decidualization, implantation, angiogenesis and maternal haemodynamics could contribute to the increased PE risk among women undergoing programmed FET cycles.Wider implicationsA better understanding of the critical roles of the secretory products of the CL during early pregnancy holds the promise of improving the efficacy and safety of ART based on programmed FET cycles.

Dataset Information

Potential influence of the corpus luteum on circulating reproductive and volume regulatory hormones, angiogenic and immunoregulatory factors in pregnant women.

Publications

Potential influence of the corpus luteum on circulating reproductive and volume regulatory hormones, angiogenic and immunoregulatory factors in pregnant women.

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