Involvement of Chemerin and CMKLR1 in the progesterone decrease by PCOS granulosa cells

Polycystic ovarian syndrome (PCOS) is the main cause of infertility in women. It is frequently associated with reduced progesterone production by human luteinised granulosa cells (hlGCs). However, the molecular mechanisms involved in these steroidogenesis alterations in PCOS patients are unclear. In a dihydrotestosterone-induced PCOS mouse model, steroid production is maintained in the setting of chemokine-like receptor 1 (CMKLR1) knockout. Thus, chemerin and chemerin receptors in terms of expression and progesterone regulation could be different in control and PCOS hlGCs. We firstly confirmed that progesterone levels in both plasma (p < 0.0001) and follicular fluid (FF) (p < 0.0001) were significantly reduced in PCOS normal weight women compared to control women. These data were associated with a lower STAR mRNA expression in both in vivo (p < 0.0001) and in vitro (p < 0.0001) hlGCs from PCOS women. Secondly, chemerin FF levels (p < 0.0001) and RARRES2 (p < 0.05) and CMKLR1 (p < 0.0001) mRNA levels in GCs were higher in PCOS normal weight patients. Thirdly, treatment of hlGCs with a specific nanobody (the VHH CA4910) targeting the human receptor for CMKLR1 leading to its inactivation, abolished chemerin-induced progesterone inhibition, suggesting the involvement of CMKLR1 in this process. Furthermore, the inhibition of progesterone secretion induced by chemerin was two-fold higher in PCOS hlGCs (p < 0.05). Moreover, the VHH CA4910 reinstated a normal progesterone secretion with lower concentrations in PCOS hlGCs, suggesting a different chemerin sensitivity between PCOS and control hlGCs. Thus, chemerin, through CMKLR1, could be involved in the steroidogenesis alterations in PCOS hlGCs.

Plasma progesterone secretion during gestation of the captive short-beaked echidna

This study describes the progesterone profile during pregnancy in sexually mature female captive short-beaked echidnas (Tachyglossus aculeatus aculeatus). Echidnas were monitored daily by video surveillance to confirm key reproductive behaviour. Plasma samples were collected and pouch morphology was assessed three times a week. The pouch of the female echidna only develops during gestation and it was possible to create a four-stage grading system using the most distinguishable characteristics of pouch development. Maximum pouch development was associated with declining progesterone concentrations, with the pouch closing in a drawstring-like manner at oviposition. Control of pouch development in pregnant echidnas is not yet clear but later pouch development is associated with a decrease in progesterone and pouch closure and may be under mechanical influences of the egg or young in the pouch. The length of pregnancy was 16.7 ± 0.2 days with a 15.1 ± 1.0 days luteal phase followed by an incubation period in the pouch. Eggs could be detected in utero at least 4 days before oviposition. Plasma progesterone peaked at 10.5 ± 0.9 ng/mL within 12 days of mating but then declined to basal levels within 1 day of oviposition and remained basal throughout egg incubation, confirming that progesterone is elevated throughout pregnancy and that gestation does not extend beyond the luteal phase. After the loss of an egg or pouch young, most females entered a second oestrous cycle and ovulated, suggesting echidnas are seasonally polyoestrous. The duration of the luteal phase in the echidna corresponds with that observed in other mammals.

Latest Advances in Sow Nutrition during Early Gestation

In the pig, the establishment and maintenance of luteal function in early gestation is crucial to endometrial function, embryo development, and survival. The level of feed intake has a positive effect on formation of luteal tissue and progesterone secretion by the ovaries in the pre-implantation period, which is important for endometrial remodeling and secretion. These effects are independent of luteinising hormone (LH) and probably driven by metabolic cues, such as insulin and insulin-like growth factor (IGF-1), and seem to support progesterone secretion and delivery to the endometrium, the latter which occurs directly, bypassing the systemic circulation. Even after implantation, a high feed intake seems to improve embryo survival and the maintenance of pregnancy. In this stage, luteal function is LH-dependent, although normal variations in energy intake may not result in pregnancy failure, but may contribute to nutrient supply to the embryos, since in this phase uterine capacity becomes limiting. Feed incidents, however, such as unintended fasting of animals or severe competition for feed, may result in embryo or even pregnancy loss, especially in periods of seasonal infertility. Specific nutrients such as arginine have a role in the vascularisation of the placenta and can improve the uterine capacity in the period after implantation.

Luteal phase deficiency: pathophysiology and role in reproductive disorders

It is well known that corpus luteum normal functioning is crucial for the luteal phase, which determines the embryo implantation and the progression of pregnancy. Luteal phase deficiency (LPD), associated with impaired progesterone secretion by the corpus luteum, is considered as a significant factor of infertility and early pregnancy loss, both in the natural cycle and in assisted reproductive technology (ART) programs. The LPD formation is associated with hypothalamic-pituitary-ovarian axis dysregulation, which leads to abnormal secretion of FSH, LH, ovulation and luteinization disorders, premature luteolysis. The most significant problem in the study of LPD is the lack of reliable and reproducible methods of its verification. This review summarizes the available data on the methods and issues of LPD diagnosing, including the duration of the luteal phase, the level of progesterone secretion, and endometrial biopsy. LPD is an important factor in reproductive failures during IVF, which is caused by suppression of the physiological FSH, LH secretion and requires mandatory progesterone support in the luteal phase of the cycle. It’s hard to define the contribution of LPD to miscarriage, however, empirical progestogen therapy may increase the live births rate in women with recurrent pregnancy loss. Currently, there is no evidence of the LPD role and progesterone support effectiveness in infertility management, so the diagnosis and therapy of LPD among these patients should not be considered.

Orexin A promotes progesterone secretion in luteinized granulose cells of Mongolian Ovis aries ovary by PRRT2 and ABCG1 genes

Summary To study the role of orexin A in the reproductive regulation of Mongolian sheep, ovine ovarian granulosa cells were cultured in vitro. The cells were divided into groups after luteinization, the experimental group was given orexin A and the transcriptome was sequenced together with that of the control group. The different genes related to reproduction were screened out. qRT-PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the selected genes and detect the effect on progesterone secretion. In total, 123 differentially expressed genes were obtained by sequencing. Six genes with high expression related to reproduction (PRRT2, ABCG1, SOX4, TBX3, ID1 and ATP8) were screened. The results of qRT-PCR were consistent with those of sequencing; western blot and ELISA were used to verify the protein levels of steroidogenic acute regulatory protein (StAR) and its related PRRT2 and ABCG1, and to detect their effect on progesterone secretion. Validation results were consistent with those of qRT-PCR and sequencing. The experimental group was given orexin A and compared with the control group. Expression of PRRT2 protein was significantly increased (P < 0.05), ABCG1 protein expression was significantly decreased (P < 0.05), StAR expression was significantly increased (P < 0.05), and progesterone secretion was significantly increased (P < 0.05). The results showed that orexin A promoted the expression of StAR by upregulating PRRT2 and downregulating ABCG1, therefore affecting secretion of progesterone. Gene expression characteristics of orexin A affecting progesterone secretion were preliminarily explored; this study provides a theoretical basis for further study on signalling pathways and reproductive regulation in Mongolian sheep.