Risk factors for cesarean section of the second twin after vaginal delivery of the first twin.

PURPOSE: To document risk factors for combined delivery, defined as unplanned cesarean section for the second twin after vaginal delivery of the first twin, particularly focusing on delivery interval between twins. METHODS: A multi-center cross-sectional study among a cohort of 5411 women with twin pregnancy experiencing vaginal delivery of the first twin in 2007-2016 at 191 tertiary referral hospitals in Japan was conducted. Primary outcome was the occurrence of combined delivery, and data were collected through the Japan Society of Obstetrics and Gynecology perinatal database. Risk factors for combined delivery were investigated using Poisson regression analysis. RESULTS: Combined delivery occurred in 235 women (5.1%) and was significantly associated with delivery interval (P < 0.001). Multivariate analysis showed women with ≥ 25 kg/m2 pre-pregnancy body mass index (BMI) and with birthweight < 1500 g of the second twin had significantly higher risk for combined delivery than women with 18.5-25 kg/m2 pre-pregnancy BMI and with birthweight ≥ 2500 g of the second twin (adjusted risk ratio (aRR) 1.72, 95% confidence interval (CI) 1.15-2.57, and aRR 2.06, 95% CI 1.14-3.72, respectively). Breech and transverse presentation of the second twin were also risk factors for combined delivery compared with cephalic presentation (aRR 3.60, 95% CI 2.67-4.85, and aRR 9.94, 95% CI 6.50-15.0, respectively). Although association of combined delivery with pre-pregnancy BMI was attenuated after adjustment by delivery interval, association with birthweight of the second twin was strengthened. CONCLUSION: Delivery interval was significantly associated with combined delivery and mediated the association between combined delivery and some other risk factors.

Association between gestational weight gain and chronic disease risks in later life.

To assess the association between gestational weight gain (GWG) and the risk of developing chronic diseases in later life, this historical cohort study of 318 non-overweight women was conducted between April 2017 and November 2020 at a hospital in Tokyo. Data about GWG in the last pregnancy and the development of any chronic diseases of the subjects were retrieved from the women's Maternal and Child Health Handbooks and through a questionnaire survey, respectively. The outcomes were chronic diseases, such as diabetes mellitus (DM), hypertension, hyperlipidemia, and being overweight (body mass index [BMI] ≥ 25 kg/m2). Association between GWG and outcomes were assessed using a logistic regression analysis.There were significant positive linear associations between GWG and the risks of developing DM, hypertension, and being overweight (P = 0.013, 0.050, and 0.017, respectively). After adjusting for later-life BMI, a significant association between GWG and DM (P = 0.025) remained, but the association between GWG and hypertension disappeared. GWG was significantly associated with DM, hypertension, and being overweight later in life. Although the association between GWG and DM was partially independent of BMI later in life, the association between GWG and hypertension was influenced by being overweight later in life.

Clinical features of fetal hydrothorax associated with mucopolysaccharidosis-VII.

Mucopolysaccharidosis (MPS)-VII, called Sly disease, is a lysosomal storage disorder that can cause fetal hydrops, including fetal hydrothorax (FHT). We describe two fetal cases that received thoracoamniotic shunting for FHT, which was later found to be associated with MPS-VII by exome sequencing. Bilateral FHT accompanied by skin edema and ascites was found before 20 weeks of gestation in both cases. One fetus died in utero at 35 weeks of gestation, and the other survived with preterm delivery at 30 weeks of gestation. Both cases inherited compound pathogenic variants of GUSB from parents. Comparison with previously reported primary FHT cases revealed distinct clinical features in MPS-VII-associated FHT: early gestational age at diagnosis (<26 weeks), bilateral effusion, skin edema with ascites, and poor survival. A genetic analysis would be considered for FHT cases, with consideration of shunting when they show early-onset bilateral effusions with skin edema and ascites.

Ultrasound measurement of umbilical venous flow volume at the intra-abdominal portion in normal fetuses.

PURPOSE: Umbilical venous flow volume (UVFV) measured using ultrasound can be used to assess placental circulation in a fetus. UVFV measured at the intra-abdominal portion using half the maximum flow velocity of the umbilical vein (UV) has good reproducibility with low variance. However, reference values in previous reports were based on a small number of cases with a wide reference range. In the present study, we evaluated UVFV standard values measured at the intra-abdominal portion in normal Japanese fetuses. METHODS: Measurements were performed on normal pregnant women during routine ultrasound screening at around 20 or 30 weeks of gestation. The diameter and flow velocity of the UV were measured at the fetal abdomen point between the insertion of the UV and branches of the portal vein. UVFV (ml/min) was calculated as follows: (UV diameter [cm]/2)2 × maximum velocity [cm/s] × 0.5 × 3.14 × 60). RESULTS: A total of 278 pregnant women were included in the study. UVFV increased with gestational weeks, and UVFV per estimated fetal weight (EFW) slightly decreased with increasing gestational weeks. The 50th (10th-90th) percentiles of UVFV per EFW at 20, 25, and 30 weeks of gestation were 130 (105-165), 123 (94-147), and 104 (80-131) ml/min/kg, respectively. CONCLUSION: New UVFV reference values measured at the intra-abdominal portion of fetuses using large-scale samples were established. Future studies should assess fetuses under pathologic conditions using UVFV reference values.

High-performance optical control of GPCR signaling by bistable animal opsins MosOpn3 and LamPP in a molecular property-dependent manner.

Optical control of G protein-coupled receptor (GPCR) signaling is a highly valuable approach for comprehensive understanding of GPCR-based physiologies and controlling them precisely. However, optogenetics for GPCR signaling is still developing and requires effective and versatile tools with performance evaluation from their molecular properties. Here, we systematically investigated performance of two bistable opsins that activate Gi/Go-type G protein (mosquito Opn3 (MosOpn3) and lamprey parapinopsin (LamPP)) in optical control in vivo using Caenorhabditis elegans. Transgenic worms expressing MosOpn3, which binds 13-cis retinal to form photopigments, in nociceptor neurons showed light-induced avoidance responses in the presence of all-trans retinal, a retinal isomer ubiquitously present in every tissue, like microbial rhodopsins and unlike canonical vertebrate opsins. Remarkably, transgenic worms expressing MosOpn3 were ~7,000 times more sensitive to light than transgenic worms expressing ChR2 in this light-induced behavior, demonstrating the advantage of MosOpn3 as a light switch. LamPP is a UV-sensitive bistable opsin having complete photoregenerative ability by green light. Accordingly, transgenic worms expressing LamPP in cholinergic motor neurons stopped moving upon violet light illumination and restored coordinate movement upon green light illumination, demonstrating color-dependent control of behavior using LamPP. Furthermore, we applied molecular engineering to produce MosOpn3-based tools enabling light-dependent upregulation of cAMP or Ca2+ levels and LamPP-based tool enabling clamping cAMP levels color dependently and context independently, extending their usability. These findings define the capacity of two bistable opsins with similar retinal requirement as ChR2, providing numerous strategies for optical control of various GPCR-based physiologies as well as GPCR signaling itself.

Molecular Mechanisms Underlying Twin-to-Twin Transfusion Syndrome.

Twin-to-twin transfusion syndrome is a unique disease and a serious complication occurring in 10-15% of monochorionic multiple pregnancies with various placental complications, including hypoxia, anemia, increased oxidative stress, and ischemia-reperfusion injury. Fetoscopic laser photocoagulation, a minimally invasive surgical procedure, seals the placental vascular anastomoses between twins and dramatically improves the survival rates in twin-to-twin transfusion syndrome. However, fetal demise still occurs, suggesting the presence of causes other than placental vascular anastomoses. Placental insufficiency is considered as the main cause of fetal demise in such cases; however, little is known about its underlying molecular mechanisms. Indeed, the further association of the pathogenic mechanisms involved in twin-to-twin transfusion syndrome placenta with several molecules and pathways, such as vascular endothelial growth factor and the renin-angiotensin system, makes it difficult to understand the underlying pathological conditions. Currently, there are no effective strategies focusing on these mechanisms in clinical practice. Certain types of cell death due to oxidative stress might be occurring in the placenta, and elucidation of the molecular mechanism underlying this cell death can help manage and prevent it. This review reports on the molecular mechanisms underlying the development of twin-to-twin transfusion syndrome for effective management and prevention of fetal demise after fetoscopic laser photocoagulation.

Quantitative assessment of coat-hanger ribs detected on three-dimensional ultrasound for prenatal diagnosis of Kagami-Ogata syndrome.

Kagami-Ogata syndrome (KOS14) is a rare disease characterized by omphalocele, polyhydramnios and a bell-shaped thorax. Although the coat-hanger appearance of the ribs on postnatal X-rays is a key diagnostic finding of KOS14, its prenatal diagnosis remains challenging. We encountered a case of KOS14 diagnosed prenatally that showed omphalocele, polyhydramnios, and a bell-shaped narrow thorax. The coat-hanger angle (CHA) measured at the sixth thoracic vertebrae and the ribs using three-dimensional (3D) ultrasonography was 39°, reflecting the coat-hanger appearance of the ribs. Segmental uniparental disomy chromosome 14 (UPD(14)pat) was confirmed by a methylation analysis and microsatellite analysis after birth. The median CHA (minimum, maximum) in 25 normal fetuses was 19 (9, 26) degrees, and a sonographic CHA of 30° may be a border value for diagnosing KOS14. When the combination of omphalocele and polyhydramnios is found prenatally, 3D ultrasonography for CHA might aid in the differential diagnosis of KOS14.

A fetus with large mediastinal cystic lymphatic malformation managed with prenatal serial thoracocentesis and postnatal sclerotherapy.

We report a very rare case of large fetal mediastinal cystic lymphatic malformation (cLM), formerly called lymphangioma, that was managed with prenatal serial thoracocentesis and postnatal sclerotherapy. A fetal pericardial effusion-like lesion gradually increased the size until it occupied more than half of the thoracic cavity. Thoracocentesis was performed three times, namely at 31 and 35 weeks of gestation, and also just before the delivery for decompression. The characteristic shape changes of the lesion were observed after thoracocentesis. A boy delivered by planned cesarian section at term required respiratory support after birth. Postnatal magnetic resonance imaging (MRI), which showed a large cystic lesion with septa and hemorrhage without solid components, led to the diagnosis of cLM. The fluid from the cyst continued to be drained. Neonatal sclerotherapy using OK-432 was effective and the infant recovered well. Fetal thoracocentesis may be useful for the diagnosis and management of a large mediastinal cLM.

New challenges of fetal therapy in Japan.

AIM: To review new challenges of fetal therapy in Japan after the establishment of four existing fetal therapies as standard prenatal care with National Health Insurance coverage over the past 20 years. METHODS: Reported studies and our current research activities related to four fetal therapies newly performed in Japan were reviewed. RESULTS: Fetoscopic endoluminal tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) aims to occlude the trachea using a detachable balloon to promote lung growth. Following the recent successful completion of an international randomized controlled trial for CDH, in which we participated, FETO is offered for severe left CDH to perform balloon insertion at 27-29 weeks and removal at 34 weeks of gestation. Fetal cystoscopy (FC) for low urinary tract obstruction was introduced to overcome the demerits of vesicoamniotic shunting. FC may provide a proper diagnosis by visual observation of the urethra and physiological treatment of the posterior urethral valve. The effectiveness of open fetal surgery for myelomeningocele (MMC), direct surgery with laparotomy and hysterotomy, for ameliorating hindbrain herniation and the motor function was demonstrated, but it was also associated with substantial maternal and fetal risks. Fetal aortic valvuloplasty (FAV), ultrasound-guided fetal aortic balloon dilation for critical aortic stenosis with evolving hypoplastic left heart syndrome may improve left heart development and maintain biventricular circulation. Feasibility and safety studies for FC, MMC open fetal surgery, and FAV are currently ongoing. CONCLUSIONS: Clinical research on FETO, FC, MMC open fetal surgery, and FAV has proceeded with careful preparations in Japan.

Disseminated intravascular coagulation complicated by amniotic band syndrome associated with deceased fetal umbilical cord following fetoscopic laser surgery.

Fetoscopic laser surgery occasionally causes amniotic band syndrome, in which the disrupted amniotic membrane constricts fetal body parts, leading to functional or morphological loss. We report a case of fetal distress at 31 weeks of gestation in the larger surviving twin after fetoscopic laser surgery for selective intrauterine growth restriction, necessitating emergent cesarean section. Physical examination of the infant showed constriction rings caused by a disrupted amniotic membrane on the digits, and the distal part of the right index finger was necrotic because of tight strangulation by an amniotic band with the umbilical cord of the deceased smaller twin. Laboratory data showed severe coagulopathy, and the infant was diagnosed with disseminated intravascular coagulation (DIC). Immediate treatment improved his condition. DIC may have been associated with the necrotic finger, which was strangulated by the umbilical cord of the deceased fetus, because neither maternal coagulopathy nor an underlying neonatal disorder was detected.

Confined placental mosaicism of trisomy 6 detected through genome-wide NIPT was associated with placental abruption.

Confined placental mosaicism (CPM) leads to discordant noninvasive prenatal testing (NIPT) results. We describe a very rare case of CPM of trisomy 6 detected through genome-wide NIPT. This case was associated with placental abruption, which might suggest an association between certain types of CPM detected by NIPT and pregnancy complications.

Insights into the evolutionary origin of the pineal color discrimination mechanism from the river lamprey.

BACKGROUND: Pineal-related organs in cyclostomes, teleosts, amphibians, and reptiles exhibit color opponency, generating antagonistic neural responses to different wavelengths of light and thereby sensory information about its "color". Our previous studies suggested that in zebrafish and iguana pineal-related organs, a single photoreceptor cell expressing both UV-sensitive parapinopsin and green-sensitive parietopsin generates color opponency in a "one-cell system." However, it remains unknown to what degree these opsins and the single cell-based mechanism in the pineal color opponency are conserved throughout non-mammalian vertebrates. RESULTS: We found that in the lamprey pineal organ, the two opsins are conserved but that, in contrast to the situation in other vertebrate pineal-related organs, they are expressed in separate photoreceptor cells. Intracellular electrophysiological recordings demonstrated that the parietopsin-expressing photoreceptor cells with Go-type G protein evoke a depolarizing response to visible light. Additionally, spectroscopic analyses revealed that parietopsin with 11-cis 3-dehydroretinal has an absorption maximum at ~570 nm, which is in approximate agreement with the wavelength (~560 nm) that produces the maximum rate of neural firing in pineal ganglion cells exposed to visible light. The vesicular glutamate transporter is localized at both the parietopsin- and parapinopsin-expressing photoreceptor terminals, suggesting that both types of photoreceptor cells use glutamate as a transmitter. Retrograde tracing of the pineal ganglion cells revealed that the terminal of the parietopsin-expressing cells is located close enough to form a neural connection with the ganglion cells, which is similar to our previous observation for the parapinopsin-expressing photoreceptor cells and the ganglion cells. In sum, our observations point to a "two-cell system" in which parietopsin and parapinopsin, expressed separately in two different types of photoreceptor cells,  contribute to the generation of color opponency in the pineal ganglion cells. CONCLUSION: Our results indicate that the jawless vertebrate, lamprey, employs a system for color opponency that differes from that described previously in jawed vertebrates. From a physiological viewpoint, we propose an evolutionary insight, the emergence of pineal "one-cell system" from the ancestral "multiple (two)-cell system," showing the opposite evolutionary direction to that of the ocular color opponency.

Awareness of paternal age effect disorders among Japanese pregnant women: implications for prenatal genetic counseling for advanced paternal age.

The increasing prevalence of advanced paternal age (APA) has mirrored the rise in maternal age. APA is associated with an increased risk of de novo pathogenic single-nucleotide variants, but this topic has been much less frequently discussed than advanced maternal age (AMA). To explore the awareness of pregnant women regarding paternal age effect (PAE) disorders, a self-administered questionnaire survey was conducted for pregnant women at their first prenatal visit before 17 weeks of gestation. A total of 120 valid respondents (95.2%) were included in the analyses. Of these, 63.3% of pregnant women were aware of PAE disorders. This was markedly lower than the 90.8% recognition of maternal age effect (MAE) disorders. One-third of women with awareness of MAE disorders were not aware of PAE disorders. Pregnant women who were parous, older than their male partners, with knowledge of prenatal testing prior to this pregnancy, and with experience of prenatal testing in a prior pregnancy were significantly more aware of PAE disorders than others. Awareness of PAE disorders was not associated with undergoing prenatal testing during the present pregnancy. Our results show that the prevalence of pregnant women's awareness of PAE disorders was lower than that of MAE disorders. The current study served as a preliminary baseline of information about pregnant women's awareness of PAE disorders. With the introduction of non-invasive prenatal testing, which has the potential to identify PAE disorders, these findings will help the development of a framework for comprehensive prenatal genetic counseling for APA pregnancies.

Long-term neurodevelopmental outcomes of the pump twin in twin reversed arterial perfusion sequence treated by radiofrequency ablation.

OBJECTIVES: To assess long-term neurodevelopmental outcomes in children after radiofrequency ablation (RFA) for twin reversed arterial perfusion (TRAP) sequence. METHODS: This cross-sectional study included children who underwent RFA for the TRAP sequence between 2012 and 2018. We assessed neurodevelopment in children using the Kinder Infant Development Scale, a validated questionnaire. The developmental quotient (DQ) assessed in nine subscales was calculated as the developmental age divided by the chronological age. Neurodevelopmental delay (NDD) was defined as a DQ of <70 points. RESULTS: In total, 38 children from 37 pregnancies underwent RFA for the TRAP sequence during the study period; 6 fetuses died in utero. We sent the questionnaire to the parents of the 32 surviving children and obtained answers for 27 (84%). The median age at the assessment was 2 years and 5 months old. The median total DQ was 111 (80-150). Most median DQs in the nine subscales were above 70. The incidence of NDD was 0% (0/27). There were no marked differences in DQ by chorionicity. CONCLUSIONS: Children who survived after RFA for TRAP sequence showed favorable long-term neurodevelopmental outcomes. Radiofrequency ablation seems to rarely affect fetal neurodevelopment. Pregnant women with TRAP sequence are encouraged to be treated by RFA.

Outcomes of fetoscopic laser surgery for twin-to-twin transfusion syndrome between 26 and 27 weeks of gestation in Japan.

AIM: The purpose of this study was to investigate the outcomes of fetoscopic laser photocoagulation (FLP) for twin-to-twin transfusion syndrome (TTTS) in Japan. METHODS: The retrospective cohort study (2012-2018) was conducted in monochorionic twin pregnancies that underwent FLP for TTTS between 26 and 27 weeks from 2012 to 2018. The perioperative data, maternal complications, gestational age (GA) at delivery, neonatal complications, and survival of infants at 28 days of age were analyzed. At term-equivalent age, severe neurological complications were identified by imaging study. RESULTS: Of 644 patients, 28 (4.3%) underwent FLP between 26 and 27 weeks, and 26 were analyzed. FLP procedures were technically successful in all cases. There were no cases of major maternal complications after surgery. Preterm rupture of membranes occurred in 34.6% of cases, and the mean GA at delivery was 33.2 ± 3.1 weeks. The survival of both twins was found in 23 (88.4%) cases, and the perinatal survival rate of at least one twin at 28 days of age was 100%. Severe neurological complications were found in six (12.2%) cases out of 49. CONCLUSIONS: FLP for TTTS between 26 and 27 weeks provided a good prognosis and caused no major maternal complications. However, severe neurological findings were found in 12% of infants.

Prenatally diagnosed lower urinary tract obstruction: A 15-year experience at two tertiary centers in Japan.

AIM: To examine the outcomes of prenatally diagnosed lower urinary tract obstruction (LUTO) with current management using vesicoamniotic shunting (VAS). METHODS: A retrospective study of prenatally diagnosed LUTO before 26 weeks of gestation at two tertiary centers in Japan between March 2002 and September 2017. LUTO was diagnosed by ultrasound demonstration of an enlarged fetal bladder associated with hydronephrosis and/or hydroureters. VAS was offered for fetuses with LUTO at ≤26 weeks of gestational age, in the presence of oligohydramnios or decreasing amniotic fluid and a favorable fetal urinary analysis. RESULTS: Among 87 fetuses with LUTO, 46 (53%) were terminated before 22 weeks of gestation. Eight cases (9%) underwent VAS and one underwent fetoscopic urethrotomy. The live birth rates in the VAS and expectant groups were 100% (8/8) and 56% (18/32), respectively (p = 0.034), and the survival rates at 6 months old with a normal renal function were 38% (3/8) and 16% (5/32), respectively (p = 0.608). The etiology varied with six cases of associated anomalies among 23 diagnosed cases. Among the nine cases of posterior urethral valve (PUV), only one fetus underwent VAS at 25 weeks of gestation, ultimately surviving with mild renal dysfunction. Among the other eight cases of PUV that were managed expectantly, two died, and only one of the six survivors showed a normal renal function. CONCLUSIONS: More than half of the prenatally diagnosed LUTO cases were terminated. VAS seemed effective for achieving a perinatal survival, regardless of etiology. The outcomes were poor in cases of expectantly managed PUV.

Risk Profiling of the Solomon Technique versus Selective Technique of Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia-polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

Nationwide survey of intrauterine blood transfusion for fetal anemia in Japan.

AIM: The present study investigated the current situation regarding intrauterine blood transfusion (IUT) for fetal anemia in Japan. METHODS: We conducted a nationwide, multicenter, retrospective cohort questionnaire survey for cases that underwent IUT from 2011 to 2015. The questionnaire required perioperative information, indications, details of the procedure, procedure-related complications, and neonatal morbidity. RESULTS: A total of 100 IUT procedures were performed in 66 cases at 19 institutions during the study period. The most frequent indication of IUT was complicated monochorionic diamniotic (MCDA) twins in 28 (42.4%) cases, followed by 16 (24.2%) cases of red-cell alloimmunization, and 10 (15.2%) cases of parvovirus B19 infection. IUT was performed through the umbilical cord in the vast of majority cases (92%). Bleeding from the IUT site was the most common adverse event (40%). Two cases (2%) underwent emergency cesarean section after the procedure. There were no cases of rupture of membrane or intrauterine infection after IUT. The neonatal survival rate was 77.3% in the 66 total cases and 64% in the hydrops cases. The neonatal survival rates in MCDA twins, red-cell alloimmunization, and parvovirus B19 infection were 75%, 93.8%, and 70%, respectively. CONCLUSIONS: IUT was performed for mainly three indications in Japan: MCDA twins, red-cell alloimmunization, and parvovirus B19 infection. The incidences of severe adverse events seemed very low. The outcomes after IUT were favorable with variations in survival rates according to indications. However, further studies with long-term follow-up will be required to assess the effectiveness of IUT, especially for complicated MCDA twins.

Functional identification of an opsin kinase underlying inactivation of the pineal bistable opsin parapinopsin in zebrafish.

In the pineal organ of zebrafish larvae, the bistable opsin parapinopsin alone generates color opponency between UV and visible light. Our previous study suggested that dark inactivation of the parapinopsin photoproduct, which activates G-proteins, is important for the regulation of the amount of the photoproduct. In turn, the photoproduct is responsible for visible light sensitivity in color opponency. Here, we found that an opsin kinase or a G-protein-coupled receptor kinase (GRK) is involved in inactivation of the active photoproduct of parapinopsin in the pineal photoreceptor cells of zebrafish larvae. We investigated inactivation of the photoproduct in the parapinopsin cells of various knockdown larvae by measuring the light responses of the cells using calcium imaging. We found that GRK7a knockdown slowed recovery of the response of parapinopsin photoreceptor cells, whereas GRK1b knockdown or GRK7b knockdown did not have a remarkable effect, suggesting that GRK7a, a cone-type GRK, is mainly responsible for inactivation of the parapinopsin photoproduct in zebrafish larvae. We also observed a similar knockdown effect on the response of the parapinopsin photoreceptor cells of mutant larvae expressing the opsin SWS1, a UV-sensitive cone opsin, instead of parapinopsin, suggesting that the parapinopsin photoproduct was inactivated in a way similar to that described for cone opsins. We confirmed the immunohistochemical distribution of GRK7a in parapinopsin photoreceptor cells by comparing the immunoreactivity to GRK7 in GRK7a-knockdown and control larvae. These findings suggest that in pineal photoreceptor cells, the cone opsin kinase GRK7a contributes greatly to the inactivation of parapinopsin, which underlies pineal color opponency.