Endoplasmic Reticulum Stress and Homeostasis in Reproductive Physiology and Pathology.

The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis. During the production of functionally effective proteins, several ER-specific molecular steps sense quantity and quality of synthesized proteins as well as proper folding into their native structures. During this process, excess accumulation of unfolded/misfolded proteins in the ER lumen results in ER stress, the homeostatic coping mechanism that activates an ER-specific adaptation program, (the unfolded protein response; UPR) to increase ER-associated degradation of structurally and/or functionally defective proteins, thus sustaining ER homeostasis. Impaired ER homeostasis results in aberrant cellular responses, contributing to the pathogenesis of various diseases. Both female and male reproductive tissues undergo highly dynamic cellular, molecular and genetic changes such as oogenesis and spermatogenesis starting in prenatal life, mainly controlled by sex-steroids but also cytokines and growth factors throughout reproductive life. These reproductive changes require ER to provide extensive protein synthesis, folding, maturation and then their trafficking to appropriate cellular location as well as destroying unfolded/misfolded proteins via activating ER-associated degradation mediated proteasomes. Many studies have now shown roles for ER stress/UPR signaling cascades in the endometrial menstrual cycle, ovarian folliculogenesis and oocyte maturation, spermatogenesis, fertilization, pre-implantation embryo development and pregnancy and parturition. Conversely, the contribution of impaired ER homeostasis by severe/prolong ER stress-mediated UPR signaling pathways to several reproductive tissue pathologies including endometriosis, cancers, recurrent pregnancy loss and pregnancy complications associated with pre-term birth have been reported. This review focuses on ER stress and UPR signaling mechanisms, and their potential roles in female and male reproductive physiopathology involving in menstrual cycle changes, gametogenesis, preimplantation embryo development, implantation and placentation, labor, endometriosis, pregnancy complications and preterm birth as well as reproductive system tumorigenesis.

Gynecologic age is an important risk factor for obstetric and perinatal outcomes in adolescent pregnancies.

BACKGROUND: Adolescent pregnancy is an important public health problem. Physiological maturity affects obstetric and perinatal outcomes. Almost all assessments of adolescent pregnancies are based on chronological age. Gynecologic age (GA) is defined as age in years at conception minus age at menarche and it is an indicator of physiological maturity. AIM: To compare obstetric and perinatal outcomes between adult and adolescent pregnancies as categorized according to GA. METHODS: In this retrospective study, 233 adolescent pregnant women were divided into two groups based on GA≤3 years (101 women) and GA>3 years (132 women). Their obstetric and perinatal results were compared with 202 adult pregnancies who gave birth in the same period. FINDINGS: Gestational age at delivery, APGAR scores, birth weight, and incidence of preterm birth, admission to neonatal intensive care unit (NICU), intrauterine growth restriction, low birth weight, and premature rupture of membranes were significantly different between the study groups. Compared to adolescent pregnancies with GA>3 years, adolescent pregnancies with GA≤3 years had significantly lower birth weight, gestational age, APGAR scores, and significantly higher incidence of intrauterine growth restriction, low birth weight and admission to NICU. CONCLUSION: Low GA is associated with an increased rate of obstetric and perinatal complications in adolescent pregnancies. Although the main aim is the prevention of adolescent pregnancies, a detailed evaluation of such pregnancies including determination of the gynecological age together with a multidisciplinary approach may decrease potential complications.